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A lap tartalmának cseréje erre: {{Személy infobox |név=Ernesto Teodoro Moneta |kép=Ernesto Teodoro Moneta.jpg |képméret= |képaláírás= |születési hely=Milánó |születési dátum…
Címke: Oldal nagy része eltávolítva
1. sor:
{{Személy infobox
'''Testosterone''' is the primary [[male]] [[sex hormone]] and an [[anabolic steroid]]. In male humans, testosterone plays a key role in the development of [[Male reproductive system|male reproductive]] tissues such as [[testes]] and [[prostate]], as well as promoting [[secondary sexual characteristic]]s such as increased [[muscle]] and [[bone]] mass, and the growth of [[androgenic hair|body hair]].<ref name="Mooradian_ 1987">{{cite journal | vauthors = Mooradian AD, Morley JE, Korenman SG | title = Biological actions of androgens | journal = Endocrine Reviews | volume = 8 | issue = 1 | pages = 1–28 | date = Feb 1987 | pmid = 3549275 | doi = 10.1210/edrv-8-1-1 }}</ref> In addition, testosterone is involved in health and well-being,<ref name="pmid19707253">{{cite journal | vauthors = Bassil N, Alkaade S, Morley JE | title = The benefits and risks of testosterone replacement therapy: a review | journal = Therapeutics and Clinical Risk Management | volume = 5 | issue = 3 | pages = 427–48 | date = Jun 2009 | pmid = 19707253 | pmc = 2701485 | doi = 10.2147/tcrm.s3025}}</ref> and the prevention of [[osteoporosis]].<ref name="pmid19011293">{{cite book | vauthors = Tuck SP, Francis RM | chapter = Testosterone, bone and osteoporosis | volume = 37 | pages = 123–32 | year = 2009 | pmid = 19011293 | doi = 10.1159/000176049 | isbn = 978-3-8055-8622-1 | series = Frontiers of Hormone Research | title = Advances in the Management of Testosterone Deficiency }}</ref> Insufficient levels of testosterone in men may lead to abnormalities including frailty and bone loss.
|név=Ernesto Teodoro Moneta
|kép=Ernesto Teodoro Moneta.jpg
|képméret=
|képaláírás=
|születési hely=[[Milánó]]
|születési dátum=[[1833]]. [[szeptember 20.]]
|halál helye=[[Milánó]]
|halál dátuma= [[1918]]. [[február 10.]]<br>(84 évesen)
|nemzetiség= [[Olaszok|olasz]]
|gyermekei = -
|állampolgárság = -
|házastárs=
|sírhely = -
|szakma= újságíró, forradalmár
|kitüntetései= [[Nobel-békedíj]] (1907)
}}
'''Ernesto Teodoro Moneta''' ([[Milánó]], [[1833]]. [[szeptember 20.]] – [[Milánó]], [[1918]]. [[február 10.]]) olasz nacionalista újságíró, forradalmár, békeaktivista. [[1907]]-ben [[Louis Renault]]-val megosztva [[Nobel-békedíj]]at kapott az olasz békemozgalomban való részvételéért.
 
== Élete ==
Testosterone is a [[steroid]] from the [[androstane]] class containing a [[ketone|keto]] and [[hydroxyl]] groups at the three and seventeen positions respectively. It is [[Biosynthesis|biosynthesized]] in several steps from cholesterol and is converted in the liver to inactive metabolites.<ref name = "Luetjens_2012" /> It exerts its action through binding to and activation of the [[androgen receptor]].<ref name = "Luetjens_2012">{{cite book | editor-last1 = Nieschlag | editor-first1 = Eberhard | editor-last2 = Behre | editor-first2 = Hermann M. | editor-last3 = Nieschlag | editor-first3 = Susan | name-list-format = vanc | title = Testosterone: Action, Deficiency, Substitution | first1 = C. Marc | last1 = Luetjens | first2 = Gerhard F. | last2 = Weinbauer | pages = 15–32 | chapter = Chapter 2: Testosterone: Biosynthesis, transport, metabolism and (non-genomic) actions | chapter-url = https://books.google.com/books?id=MkrAPaQ4wJkC&pg=PA15&redir_esc=y#v=onepage&q&f=false | date = 2012 | publisher = Cambridge University Press | location = Cambridge | isbn = 978-1-107-01290-5 | edition = 4th }}</ref> In humans and most other [[vertebrate]]s, testosterone is secreted primarily by the [[testicles]] of [[male]]s and, to a lesser extent, the [[ovaries]] of [[female]]s. On average, in adult males, levels of testosterone are about 7 to 8 times as great as in adult females.<ref name="pmid14981046">{{cite journal | vauthors = Torjesen PA, Sandnes L | title = Serum testosterone in women as measured by an automated immunoassay and a RIA | journal = Clinical Chemistry | volume = 50 | issue = 3 | pages = 678; author reply 678–9 | date = Mar 2004 | pmid = 14981046 | doi = 10.1373/clinchem.2003.027565 }}</ref> As the metabolism of testosterone in males is more pronounced, the daily production is about 20 times greater in men.<ref name="pmid6025472">{{cite journal | vauthors = Southren AL, Gordon GG, Tochimoto S, Pinzon G, Lane DR, Stypulkowski W | title = Mean plasma concentration, metabolic clearance and basal plasma production rates of testosterone in normal young men and women using a constant infusion procedure: effect of time of day and plasma concentration on the metabolic clearance rate of testosterone | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 27 | issue = 5 | pages = 686–94 | date = May 1967 | pmid = 6025472 | doi = 10.1210/jcem-27-5-686 }}</ref><ref name="pmid5843701">{{cite journal | vauthors = Southren AL, Tochimoto S, Carmody NC, Isurugi K | title = Plasma production rates of testosterone in normal adult men and women and in patients with the syndrome of feminizing testes | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 25 | issue = 11 | pages = 1441–50 | date = Nov 1965 | pmid = 5843701 | doi = 10.1210/jcem-25-11-1441 }}</ref> Females are also more sensitive to the hormone.<ref name="isbn0-07-135739-4">{{cite book | vauthors = Dabbs M, Dabbs JM | title = Heroes, rogues, and lovers: testosterone and behavior | edition = | publisher = McGraw-Hill | location = New York | year = 2000 | isbn = 978-0-07-135739-5 }}</ref>
Ernesto Teodoro Moneta 1833. szeptember 20-án született, az akkor az Osztrák Császársághoz tartozó Milánóban. Elszegényedett arisztokrata családja vidéki házukba húzódott vissza, ahol - bár luxuskiadások nélkül - folytathatták korábbi életmódjukat. Tizenöt éves volt, amikor kitört az 1848-as milánói forradalom. Az apja oldalán védte meg otthonukat és az összecsapásban három osztrák katona meghalt. Ezek az események nagy hatással voltak Moneta személyiségére, amelyet egyaránt jellemzett a lelkes patriotizmus, sőt nacionalizmus, másrészt viszont elkötelezettség a béke ügye iránt. Később gyakran használták rá a "militáns pacifista" jelzőt. 1848 és 1866 között az olasz függetlenség és egyesítés ügyéért küzdött; 1859-1860-ban együtt harcolt Garibaldival, később pedig Giuseppe Sirtori tábornok oldalán, aki maga mellé vette szárnysegédnek. Az 1866-os hadjárat során (amikor a custozai vereség után veszekedés tört ki a vezérkarban és Sirtorit eltávolították a vezetői posztról) azonban csalódott a hadseregben és leszerelt.
 
Egy milánói napilapba, az Edoardo Sonzogno által 1866-ban alapított Il Secolóba kezdett színikritikákat írni. A következő évben két barátja megvásárolta az újságot, Monetát pedig felkérték főszerkesztőnek. Ezt a feladatot egészen 1895-ig ellátta. Dinamikus és idealista személyiségének köszönhetően újságjával jelentős mértékben tudta befolyásolni a közvéleményt. Ellentmondásos természete itt is kiütközött: bár hithű katolikus volt, az Il Secolo harcos antiklerikális hangvételt ütött meg, mert Moneta úgy vélte, hogy papság útjában állt az olasz egyesítésnek és az ország társadalmi fejlődésének. Emiatt mélyen vallásos felesége és két fia is elidegenedett tőle.
In addition to its role as a natural hormone, testosterone is used as a [[medication]], for instance in the treatment of [[male hypogonadism|low testosterone levels in men]], [[transgender hormone therapy]] for [[transgender men]], and [[breast cancer]] in women.<ref name=AHFS2016/> Since [[andropause|testosterone levels decrease as men age]], testosterone is sometimes used in older men to counteract this deficiency. It is also used illicitly to [[performance-enhancing substance|enhance physique and performance]], for instance in [[athlete]]s.<ref>{{cite book |last1=Therapy |first1=Institute of Medicine (US) Committee on Assessing the Need for Clinical Trials of Testosterone Replacement |last2=Liverman |first2=Catharyn T. |last3=Blazer |first3=Dan G. |title=Introduction |date=2004 |publisher=National Academies Press (US) |url=https://www.ncbi.nlm.nih.gov/books/NBK216164/ |language=en}}</ref>
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Volt katonaként azért kampányolt, hogy az újoncok hosszas és kevéssé hatékony alapkiképzése helyett még a falvakban, városokban élő fiatalokat tanítsák meg célba lőni, sportolni, amivel jelentősen le lehetett volna rövidíteni a hadseregbeli kiképzés idejét.
 
During the last thirty years of the nineteenth century, Moneta gathered material and insights for his opus Le guerre, le insurrezioni e la pace nel secolo XIX [Wars, Insurrections and Peace in the Nineteenth Century], which he published in four volumes in 1903, 1904, 1906, and 1910. The part of this work which remains of greatest interest is the first volume, in which he describes the development of the international peace movement during the course of the century. Moneta concentrates his interest on military rather than on social or economic issues throughout the work and utilizes the point of view and approach of the journalist, narrating in a first-person, anecdotal style. His recurrent theme is the lack of substantive results achieved by wars and militarism. Yet, during his career as editor of Il Secolo, Moneta was one of the most vocal nationalists in Italy. He managed to make his intense patriotism and his devotion to the cause of national defense and of Italian unification consistent with his dedication to the fostering of international peace and arbitration, becoming a full-time pacifist immediately upon his retirement from Il Secolo. Although his highly personal brand of nationalism almost approached chauvinism, he fought for years against the contempt for Austria displayed by many Il Secolo readers and against the «Gallophobia» which swept Italy during the 1880’s.
 
The range of activities in which Moneta engaged for the propagation of world peace is impressive. In 1890 he began to issue an annual almanac called L’Amico della pace. After his retirement as editor of Il Secolo, he continued to contribute to its columns from time to time and to republish many of his articles in pamphlets and periodicals. Ever aware of the value of propaganda for peace, he even printed one-page tracts and distributed them to rural schoolmasters. In 1898 he founded a fortnightly review, La Vita internazionale, which gained sufficient prestige to ensure publication on a regular basis for many years during a period when most such periodicals languished in Italy for lack of interest and financial support.
==Biológiai hatásai==
Általánosságban az androgén hormonok, mint a tesztoszteron elősegítik az androgénreceptorokkal rendelkező szövetekben a fehérjeszintézist, így a szövet növekedését.<ref name="pmid10821325">{{cite journal | vauthors = Sheffield-Moore M | title = Androgens and the control of skeletal muscle protein synthesis | journal = Annals of Medicine | volume = 32 | issue = 3 | pages = 181–6 | year = 2000 | pmid = 10821325 | doi = 10.3109/07853890008998825 }}</ref> Úgynevezett virilizáló és anabolikus hatásokat indukál.<ref>{{cite book | chapter = Androgen Physiology, Pharmacology and Abuse | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK279000/ | first = David J | last = Handelsman | name-list-format = vanc | title = Endotext Internet | work = WWW.ENDOTEXT.ORG | publisher = MDText.com, Inc | date = January 2013}}</ref>
* az ''anabolikus hatások'' többek között az izomtömeg és izomerő növekedésével, a csontsűrűség és csontszilárdság fokozódásával járnak valamint fokozzák a csontok hossznövekedését és érését.
* az ''androgén hatások'' a nemi szervek érését okozzák, vagyis a magzatban a pénisz és a herék kialakulását; serdülőkorban pedig az arc- és testszőrzet növekedését, a hang mélyülését, vagyis a másodlagos nemi jellegek kifejlődését.
 
His work for peace was not solely of a literary nature. He became the Italian representative on the Commission of the International Peace Bureau in 1895. He attended peace congresses for many years, and his courtly, deceptively diffident presence became increasingly familiar and respected. He had encouraged l’Unione lombarda per la pace e l’arbitrato internazionale [the Lombard Union for International Peace and Arbitration] since its foundation in 18871, and had himself founded, besides several organizations of an ephemeral nature, the Società per la pace e la giustizia internazionale [Society for International Peace and Justice]2, which lasted from 1887 until 19373, long after his death. He lectured at the newly founded Italian Popular University. In 1906 he planned and had constructed a Pavilion for Peace at the Milan International Exposition, during which he presided over the fifteenth annual International Peace Congress.
A tesztoszteron hatásait az életkori megjelenés sorrendjében is felsorolhatjuk. A hatások erőssége a születés után férfiakban és nőkben is nagyban függ a vérben szabadon keringő hormon koncentrációjától és az hatás időtartamának hosszától.
 
From 1900 until his death in 1918, Moneta suffered from glaucoma, and he spent long periods in the country recuperating from eye operations which barely prevented total blindness. Physical suffering refined Moneta’s high sense of purpose but did not diminish his essential exuberance, even in advanced age, or his ability to state vigorously his convictions. During World War I, for example, supporting Italy’s role in the war, he said4: «I, as an Italian, cannot put myself au dessus de la mêlée. I must participate in the life of my country, rejoice in her joys, and weep in her sorrows.»
===Születés előtt===
A tesztoszteron az embrionális fejlődés két szakaszában játszik jelentős szerepet.
 
Moneta succumbed to pneumonia in 1918 at the age of eighty-five. The monument which his friends erected to him in 1925 was carted off to a warehouse during the Fascist regime, thus escaping destruction when a bomb fell on the site during World War II. The inscription on its base preserves the essential paradox of his life, for it honors him both as a partisan of Garibaldi’s and as an apostle of peace.
Az első periódus a terheség 4-6. hétében játszódik le, amikor a nemi szervek, valamint a húgycső péniszbeli szakasza, a herezacskó kialakulnak. Ebben a szakaszban a dihidritesztoszteron játssza a fő szerepet. Ekkor formálódik a prosztata és az ondóhólyag is.
Selected Bibliography
Combi, Maria, Ernesto Teodoro Moneta: Premio Nobel per la pace 1907. Milano, Mursia, 1968.
Moneta, Ernesto Teodoro, Dal presente all’ avvenrie, Milano, 1913.
Moneta, Ernesto Teodoro, Le guerre, le insurrezioni e la pace nel secolo decimonono, Compedio storico. 4 vols. Milano, 1903-1910.
Moneta, Ernesto Teodoro, L’ideale della pace e la patria. Milano, 1913.
Moneta, Ernesto Teodoro, Irredentismo e gallophia. Milano, 1903.
Moneta, Ernesto Teodoro, La nostra pace. Milano, Bellini, 1909.
Moneta, Ernesto Teodoro, Patria e umanità. Milano, Sonzogno, 1899.
Pinardi, Giuseppe, La Carrière d’un pacifiste: E. T. Moneta. Le Havre, Publication de «L’Universel», 1904.
Schou, August, Histoire de l’internationalisme III: Du Congrès de Vienne jusqu’à la première guerre mondiale (1914), pp. 355-359. Publications de l’Institut Nobel Norvégien, Tome VIII. Oslo, Aschehoug, 1963.
 
== Források ==
A második torimeszter során alakulnak ki a magzat nemi jellegei és ebben a folyamatban is kulcsszerepet játszanak az androgén hormonok.<ref name="pmid19403051">{{cite journal | vauthors = Swaab DF, Garcia-Falgueras A | title = Sexual differentiation of the human brain in relation to gender identity and sexual orientation | journal = Functional Neurology | volume = 24 | issue = 1 | pages = 17–28 | year = 2009 | pmid = 19403051 | doi = }}</ref> Az ekkori hormonszint nagyobb hatással van a későbbi felnőtt nemi viselkedésére, mint a felnőttkori hormonszint.<ref>{{cite journal|last1=Berenbaum|first1=Sheri A.|title=Beyond Pink and Blue: The Complexity of Early Androgen Effects on Gender Development|journal=Child Development Perspectives|date=March 2018|volume=12|issue=1|pages=58–64|doi=10.1111/cdep.12261|pmid=29736184|pmc=5935256}}</ref> Például a veleszületett mellékvese-megnagyobbodásban szenvedő nőkre inkább jellemző gyerekkorban a fiús játékok kedvelése, felnőttként pedig csökkent heteroszexuális érdeklődést mutatnak a férfiak iránt.<ref>{{cite journal|last1=Hines|first1=Melissa|last2=Brook|first2=Charles|last3=Conway|first3=Gerard S.|title=Androgen and psychosexual development: core gender identity, sexual orientation and recalled childhood gender role behavior in women and men with congenital adrenal hyperplasia (CAH)|journal=Journal of Sex Research|date=February 2004|volume=41|issue=1|pages=75–81|doi=10.1080/00224490409552215|pmid=15216426}}</ref>
*[https://www.nobelprize.org/prizes/peace/1902/gobat/biographical/ Albert Gobat - Biographical] ''Nobelprize.org''
 
*[https://www.britannica.com/biography/Charles-Albert-Gobat Charles-Albert Gobat] ''Encyclopedia Britannica''
===Csecsemőkor===
{{NobelBékeDíj}}
Az androgének hatásai közül a kora csecsemőkoriak a legkevésbé feltártak. A fiúgyermekek születés utáni első heteiben a tesztoszteronszint megnő és néhány hónapig olyan magas, mint amilyen a serdülőkorra jellemző. A 4-7. hónapra a hormonkoncentráció visszaesik az alig detektálható szintre, ami aztán az egész gyermekkorra jellemző marad.<ref name="pmid4715291">{{cite journal | vauthors = Forest MG, Cathiard AM, Bertrand JA | title = Evidence of testicular activity in early infancy | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 37 | issue = 1 | pages = 148–51 | date = Jul 1973 | pmid = 4715291 | doi = 10.1210/jcem-37-1-148 }}</ref><ref name="pmid1379488">{{cite journal | vauthors = Corbier P, Edwards DA, Roffi J | title = The neonatal testosterone surge: a comparative study | journal = Archives Internationales de Physiologie, de Biochimie et de Biophysique | volume = 100 | issue = 2 | pages = 127–31 | year = 1992 | pmid = 1379488 | doi = 10.3109/13813459209035274 }}</ref> Ennek az ideiglenes növekedésnek az oka nem ismert; feltételezik, hogy az agy maszkulinizációjához szükséges, ugyanis más szervek változását nem sikerült megfigyelni.<ref name="pmid18445234">{{cite journal | vauthors = Dakin CL, Wilson CA, Kalló I, Coen CW, Davies DC | title = Neonatal stimulation of 5-HT(2) receptors reduces androgen receptor expression in the rat anteroventral periventricular nucleus and sexually dimorphic preoptic area | journal = The European Journal of Neuroscience | volume = 27 | issue = 9 | pages = 2473–80 | date = May 2008 | pmid = 18445234 | doi = 10.1111/j.1460-9568.2008.06216.x }}</ref> Az agy maszkulinizációja úgy történik, hogy a tesztoszteron egyik széngyűrűje aromatizálásával ösztrogénné alakul át, amely át tud hatolni a vér-agy gáton és utána kapcsolódni tud az idegsejtek receptoraihoz; a lányoknál ez a folyamat nem történik meg, mert náluk az [[alfa-fetoprotein]] megköti az ösztrogént.<ref name="isbn0-495-60300-7">{{cite book | vauthors = Kalat JW | title = Biological psychology | publisher = Wadsworth, Cengage Learning | location = Belmont, Calif | year = 2009 | isbn = 978-0-495-60300-9 | chapter = Reproductive behaviors | chapterurl =https://books.google.com/books?id=ZlSbk5rUY60C&lpg=PA321&ots=PUbcHTdh-A&pg=PA321#v=onepage&q&f=false | page = 321 }}</ref>
{{Nemzetközi katalógusok}}
 
===Serdülőkor===
A serdülőkor kezdetén a növekvő andrgénszint már érezteti a hatását, mind a fiúkban, mind a lányokban. Ezek közé tartozik a felnőttekre jellemző testszag, a bőr és a haj zsírosabbá válása, a pattanások, a fanszőrzet és a hónaljszőrzet megjelenése, a felgyorsult növekedés.<ref name="Pinyerd_2005">{{cite journal | vauthors = Pinyerd B, Zipf WB | title = Puberty-timing is everything! | journal = Journal of Pediatric Nursing | volume = 20 | issue = 2 | pages = 75–82 | year = 2005 | pmid = 15815567 | doi = 10.1016/j.pedn.2004.12.011 }}</ref>
 
A tényleges serdülőkori hatások azután jelentkeznek, amikor az androgénszint több hónapja (vagy éve) meghaladja a felnőtt nőkre jellemző értéket. Fiúkban ezek általában késő-serdülőkori hatások, nőkben pedig jelentkezésükhöz hosszabb ideig tartó magas tesztoszteronszint szükséges. A pubertáskori hatások a következők:<ref name="Pinyerd_2005" /><ref name= "Ganong_2012">{{cite book | last1 = Ganong | title = Ganong's Review of Medical Physiology | publisher = TATA McGRAW Hill | isbn = 978-1-25-902753-6 | pages = 423–25 | edition = 24 | year = 2012 | name-list-format = vanc }}</ref>
 
A herékben a spermatogén szövet kifejlődése, a pénisz (fiúknál) és a csikló (lányoknál) növekedése, erősödő libidó. A növekedési hormon befolyásolása révén az állkapocs, áll, szemöldökcsont megerősödése és az arc kontúrjának változása.<ref name="pmid20501658">{{cite journal | vauthors = Raggatt LJ, Partridge NC | title = Cellular and molecular mechanisms of bone remodeling | journal = The Journal of Biological Chemistry | volume = 285 | issue = 33 | pages = 25103–8 | year = 2010 | pmid = 20501658 | pmc = 2919071 | doi = 10.1074/jbc.R109.041087 }}</ref> A csontfejlődés és a magasságnövekedés befejezése. Utóbbi közvetetten történik az ösztradiol metabolitjain keresztül és fiúkban fokozatosabban zajlik le, mint a lányokban. Az izomtömeg és izomerő növekedése, a vállak szélesedése, a mellkas megnagyobbodása, a hang mélyebbé válása, ádámcsutka kialakulása. A faggyúmirigyek megnagyobbodása (ami pattanások megjelenéséhez vezethet). Az arc bőr alatti zsírrétegének csökkenése. A fanszőrzet kiterjedése a combokra és a köldökig, az arcszőrzet (bajusz, szakáll) növekedése, a fejtetőn a haj gyérülése (ún androgén alopécia), testszőrzet növekedése.
 
===Felnőttkor===
A tesztoszteronra szükség van a spermiumok fejlődéshez. Aktiválja a herék Sertoli-sejtjeinek azon génjeit, amelyek elősegítik a spermatogoniumok differenciálódását. Versengési helyzetekben szabályozza a hipotalamusz-agyalapi mirigy-mellékvese rendszer hormonelválasztását.<ref name="pmid18505319">{{cite journal | vauthors = Mehta PH, Jones AC, Josephs RA | title = The social endocrinology of dominance: basal testosterone predicts cortisol changes and behavior following victory and defeat | journal = Journal of Personality and Social Psychology | volume = 94 | issue = 6 | pages = 1078–93 | date = Jun 2008 | pmid = 18505319 | doi = 10.1037/0022-3514.94.6.1078 | url = http://homepage.psy.utexas.edu/homepage/faculty/josephs/pdf_documents/index.cfm.pdf | deadurl = yes | archiveurl = https://web.archive.org/web/20090419200557/http://homepage.psy.utexas.edu/homepage/faculty/josephs/pdf_documents/index.cfm.pdf | archivedate = April 19, 2009 | df = mdy-all | citeseerx = 10.1.1.336.2502 }}</ref> Az androgén hormonok (köztük a tesztoszteron) fokozzák az izomnövekedést. A tesztoszteron befolyásolja a megakariociták és a vérlemezkék tromboxán A2 receptorainak kifejeződését, ezáltal a vérlemezkék aggregációját és a véralvadást.<ref name="pmid15820970">{{cite journal | vauthors = Ajayi AA, Halushka PV | title = Castration reduces platelet thromboxane A2 receptor density and aggregability | journal = QJM | volume = 98 | issue = 5 | pages = 349–56 | date = May 2005 | pmid = 15820970 | doi = 10.1093/qjmed/hci054 }}</ref><ref name="pmid7758179">{{cite journal | vauthors = Ajayi AA, Mathur R, Halushka PV | title = Testosterone increases human platelet thromboxane A2 receptor density and aggregation responses | journal = Circulation | volume = 91 | issue = 11 | pages = 2742–7 | date = Jun 1995 | pmid = 7758179 | doi = 10.1161/01.CIR.91.11.2742 }}</ref>
 
Hatásai a férfiakban egyértelműbben jelentkeznek, bár valószínűleg mindkét nemben fontosak. Az életkor előrehaladtával, ahogy a tesztoszteron szintje visszaesik, úgy a hatások mértéke is csökken.<ref>{{cite journal | vauthors = Kelsey TW, Li LQ, Mitchell RT, Whelan A, Anderson RA, Wallace WH | title = A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years | journal = PLOS ONE | volume = 9 | issue = 10 | pages = e109346 | date = October 8, 2014 | pmid = 25295520 | pmc = 4190174 | doi = 10.1371/journal.pone.0109346 | bibcode = 2014PLoSO...9j9346K }}</ref>
 
A magas tesztoszteronkoncentráció nem fokozza a prosztatarák kialakulásának veszélyét. Valószínűleg éppen ellenkezőleg, az alacsony hormonszíntű férfiak kockázata nagyobb és a kialakuló tumor is veszélyesebb.<ref name="pmid19011298">{{cite book | vauthors = Morgentaler A, Schulman C | chapter = Testosterone and prostate safety | volume = 37 | pages = 197–203 | year = 2009 | pmid = 19011298 | doi = 10.1159/000176054 | isbn = 978-3-8055-8622-1 | series = Frontiers of Hormone Research | title = Advances in the Management of Testosterone Deficiency }}</ref><ref>{{cite journal | vauthors = Rhoden EL, Averbeck MA, Teloken PE | title = Androgen replacement in men undergoing treatment for prostate cancer | journal = The Journal of Sexual Medicine | volume = 5 | issue = 9 | pages = 2202–08 | date = Sep 2008 | pmid = 18638000 | doi = 10.1111/j.1743-6109.2008.00925.x }}</ref><ref>{{cite journal | vauthors = Morgentaler A, Traish AM | title = Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth | journal = European Urology | volume = 55 | issue = 2 | pages = 310–20 | date = Feb 2009 | pmid = 18838208 | doi = 10.1016/j.eururo.2008.09.024 }}</ref> Idős férfiakban a tesztoszteron közvetetten segít fenntartani a szív- és érrendszer egészségét azzal, hogy gátolja az izptömeg elvesztését, gátolja az elhízást és csökkenti a koleszterinszintet.<ref name="pmid18488876">{{cite journal | vauthors = Stanworth RD, Jones TH | title = Testosterone for the aging male; current evidence and recommended practice | journal = Clinical Interventions in Aging | volume = 3 | issue = 1 | pages = 25–44 | year = 2008 | pmid = 18488876 | pmc = 2544367 | doi = 10.2147/CIA.S190}}</ref> Nők esetében a magas androgénszint együtt járhat a szabálytalan menstruációs ciklussal.<ref name="pmid17039468">{{cite journal | vauthors = Van Anders SM, Watson NV | title = Menstrual cycle irregularities are associated with testosterone levels in healthy premenopausal women | journal = American Journal of Human Biology | volume = 18 | issue = 6 | pages = 841–44 | year = 2006 | pmid = 17039468 | doi = 10.1002/ajhb.20555 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/83925/1/menstrual_cycle_irregularities_are_associated_with_testosterone_levels_in_healthy_premenopausal_women.pdf | hdl = 2027.42/83925 }}</ref>
 
Megfigyelték, hogy a tesztoszteronszint befolyásolja a kockázatvállalást a pénzügyi döntések esetében is.<ref name= "pmid19706398">{{cite journal | vauthors = Sapienza P, Zingales L, Maestripieri D | title = Gender differences in financial risk aversion and career choices are affected by testosterone | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 36 | pages = 15268–73 | date = September 2009 | pmid = 19706398 | pmc = 2741240 | doi = 10.1073/pnas.0907352106 | bibcode = 2009PNAS..10615268S }}</ref><ref name= "Apicella_2008">{{cite journal | vauthors = Apicella CL, Dreber A, Campbell B, Gray PB, Hoffman M, Little AC | title = Testosterone and financial risk preferences | journal = Evolution and Human Behavior | volume = 29 | issue = 6 | pages = 384–90 |date= November 2008 | pmid = | doi = 10.1016/j.evolhumbehav.2008.07.001 }}</ref>
 
Férfiaknál a szexuális aktivitás periódusai együttjárnak a magasabb tesztoszteron-szinttel.<ref name="pmid1275688">{{cite journal | vauthors = Kraemer HC, Becker HB, Brodie HK, Doering CH, Moos RH, Hamburg DA | title = Orgasmic frequency and plasma testosterone levels in normal human males | journal = Archives of Sexual Behavior | volume = 5 | issue = 2 | pages = 125–32 | date = Mar 1976 | pmid = 1275688 | doi = 10.1007/BF01541869 }}</ref><ref name=Roney_2003>{{cite journal | vauthors = Roney JR, Mahler SV, Maestripieri D | title = Behavioral and hormonal responses of men to brief interactions with women | journal = Evolution and Human Behavior | year = 2003 | volume = 24 | issue = 6 | pages = 365–75 | doi = 10.1016/S1090-5138(03)00053-9 }}</ref> Szexfilmek nézése után átlagosan 35%-kal nőtt s vér tesztoszteronkoncentrációja (a legmagasabb 60-90 perccel a film vége után volt);<ref>{{cite journal | vauthors = Pirke KM, Kockott G, Dittmar F | title = Psychosexual stimulation and plasma testosterone in man | journal = Archives of Sexual Behavior | volume = 3 | issue = 6 | pages = 577–84 | date = Nov 1974 | pmid = 4429441 | doi = 10.1007/BF01541140 }}</ref> ezenkívül nőtt a motiváció, a versengésre való hajlam és csökkent a kifáradtság.<ref name="pmid4001279">{{cite journal | vauthors = Hellhammer DH, Hubert W, Schürmeyer T | title = Changes in saliva testosterone after psychological stimulation in men | journal = Psychoneuroendocrinology | volume = 10 | issue = 1 | pages = 77–81 | year = 1985 | pmid = 4001279 | doi = 10.1016/0306-4530(85)90041-1 }}</ref> Megfigyelték, hogy a ciklusuk [[Ovuláció|peteérési]] szakaszában lévő nők szagának kitett férfiak hormonszintje magasabb volt, mint a kontrollcsoporté.
<ref name="pmid20424057">{{cite journal | vauthors = Miller SL, Maner JK | title = Scent of a woman: men's testosterone responses to olfactory ovulation cues | journal = Psychological Science | volume = 21 | issue = 2 | pages = 276–83 | date = Feb 2010 | pmid = 20424057 | doi = 10.1177/0956797609357733 | url = https://semanticscholar.org/paper/71e4403da354af0acb03062f9bb65d543795c1db }}</ref>
 
Az androgén hormonok a nők szexuális viselkedését is befolyásolják. Hatásuk van a hüvely szöveteinek élettanára és a nemi izgalom kialakulására.<ref name="pmid12007897">{{cite journal | vauthors = Traish AM, Kim N, Min K, Munarriz R, Goldstein I | title = Role of androgens in female genital sexual arousal: receptor expression, structure, and function | journal = Fertility and Sterility | volume = 77 Suppl 4 | issue = | pages = S11–8 | date = Apr 2002 | pmid = 12007897 | doi = 10.1016/s0015-0282(02)02978-3 }}</ref> Szexuális aktivitás során a nyálban mért tesztoszteron-koncentráció magasabb volt, mint más fizikai tevékenység esetén.<ref name="pmid17320881">{{cite journal | vauthors = van Anders SM, Hamilton LD, Schmidt N, Watson NV | title = Associations between testosterone secretion and sexual activity in women | journal = Hormones and Behavior | volume = 51 | issue = 4 | pages = 477–82 | date = Apr 2007 | pmid = 17320881 | doi = 10.1016/j.yhbeh.2007.01.003 | hdl = 2027.42/83880 }}</ref> Tesztoszterontapasszal egyes esetekben javítani lehet a női szexuális izgalom zavarain és az alacsony libidón, de erre a célra engedélyezett gyógyszer nem áll rendelkezésre. A kezelés során ügyelni kell a megfelelő ösztrogénszintre is.<ref name="Bolour_2005">{{cite journal | vauthors = Bolour S, Braunstein G | title = Testosterone therapy in women: a review | journal = International Journal of Impotence Research | volume = 17 | issue = 5 | pages = 399–408 | year = 2005 | pmid = 15889125 | doi = 10.1038/sj.ijir.3901334 }}</ref>
 
====Párkapcsolat====
A szerelmes férfiak tesztoszteronszintje csökken, míg a nőké megnövekszik; ennek oka feltehetően az, hogy a nemek viselkedése eltérő a párkeresési és a párkapcsolati szakaszban.<ref name="pmid15177709">{{cite journal | vauthors = Marazziti D, Canale D | title = Hormonal changes when falling in love | journal = Psychoneuroendocrinology | volume = 29 | issue = 7 | pages = 931–36 | date = Aug 2004 | pmid = 15177709 | doi = 10.1016/j.psyneuen.2003.08.006 }}</ref> A "rózsaszín köd" elmúlásakor azonban - kb négy évnyi kapcsolat után - ez a hatás már nem figyelhető meg.<ref name="pmid15177709" /> Kutatások szerint a párkapcsolatban vagy házasságban férfiaknak alacsonyabb a horminszintje.<ref name="pmid16621328">{{cite journal | vauthors = van Anders SM, Watson NV | title = Relationship status and testosterone in North American heterosexual and non-heterosexual men and women: cross-sectional and longitudinal data | journal = Psychoneuroendocrinology | volume = 31 | issue = 6 | pages = 715–23 | date = Jul 2006 | pmid = 16621328 | doi = 10.1016/j.psyneuen.2006.01.008 | hdl = 2027.42/83924 }}</ref><ref name = "Booth_Dabbs_1993"/> and men who produce more testosterone are more likely to divorce;<ref name = "Booth_Dabbs_1993">{{cite journal | vauthors = Booth A, Dabbs JM|title=Testosterone and Men's Marriages | journal = Social Forces | year = 1993 | volume = 72 | issue = 2 | pages = 463–77 | doi = 10.1093/sf/72.2.463}}</ref><ref name=Mazur_Michalek_1998>{{cite journal | vauthors = Mazur A, Michalek J | title = Marriage, Divorce, and Male Testosterone | journal = Social Forces | year = 1998 | volume = 77 | issue = 1 | pages = 315–30 | doi = 10.1093/sf/77.1.315 }}</ref> Azok az egyedülálló férfiak, akiknek korábban volt már barátnőjük, nagyobb hormonkoncentrációval rendelkeznek, mint azok, akiknek nem volt ilyen tapasztalatuk.<ref name=Gray_2004>{{cite journal | vauthors = Gray PB, Chapman JF, Burnham TC, McIntyre MH, Lipson SF, Ellison PT | title = Human male pair bonding and testosterone | journal = Human Nature | volume = 15 | issue = 2 | pages = 119–31 | date = Jun 2004 | pmid = 26190409 | doi = 10.1007/s12110-004-1016-6 }}</ref> A magas hormonszintű házas férfiak nagyobb eséllyel csalják meg házastársukat.<ref name=Booth_Dabbs_1993/>
 
Az apaság tovább csökkenti a férfiak tesztoszterontermelését, ami valószínűleg a gyerekneveléshez szükséges viselkedés és érzelmek kialakításához szükséges.<ref>{{cite journal | vauthors = Bribiescas RG, Ellison PT, Gray PB |date=December 2012|title=Male Life History, Reproductive Effort, and the Evolution of the Genus Homo|journal=Current Anthropology|volume=53|issue=S6|pages=S424–S435|doi=10.1086/667538}}</ref>
 
===Aggression and criminality {{anchor|Aggression}}{{anchor|Criminality}}===
{{See also|Aggression#Testosterone|Biosocial criminology}}
 
Most studies support a link between adult criminality and testosterone. Nearly all studies of juvenile delinquency and testosterone are not significant. Most studies have also found testosterone to be associated with behaviors or personality traits linked with criminality such as [[Antisocial personality disorder|antisocial behavior]] and [[alcoholism]]. Many studies have also been done on the relationship between more general aggressive behavior and feelings and testosterone. About half the studies have found a relationship and about half no relationship.<ref name="isbn0-12-373612-9">{{cite book | vauthors = Wright J, Ellis L, Beaver K | title = Handbook of crime correlates | publisher = Academic Press | location = San Diego | year = 2009 | pages =208–10 | isbn = 978-0-12-373612-3 }}</ref> Studies have also found that testosterone facilitates aggression by modulating [[vasopressin]] receptors in the [[hypothalamus]].<ref>{{cite journal | vauthors = Delville Y, Mansour KM, Ferris CF | title = Testosterone facilitates aggression by modulating vasopressin receptors in the hypothalamus | journal = Physiology & Behavior | volume = 60 | issue = 1 | pages = 25–9 | date = July 1996 | pmid = 8804638 | doi = 10.1016/0031-9384(95)02246-5 }}</ref>
 
Testosterone is significantly discussed in relation to aggression and competitive behavior. There are two theories on the role of testosterone in aggression and competition.<ref name=":0">{{cite journal | vauthors = Archer J | title = Testosterone and human aggression: an evaluation of the challenge hypothesis | journal = Neuroscience and Biobehavioral Reviews | volume = 30 | issue = 3 | pages = 319–45 | date = 2006 | pmid = 16483890 | doi = 10.1016/j.neubiorev.2004.12.007 | url = http://www.homepage.psy.utexas.edu/homepage/faculty/josephs/pdf_documents/Arch_Chall_NBR.pdf | url-status = dead | archiveurl = https://web.archive.org/web/20160109111144/http://www.homepage.psy.utexas.edu/HomePage/faculty/josephs/pdf_documents/Arch_Chall_NBR.pdf | archivedate = January 9, 2016 | df = mdy-all }}</ref> The first one is the [[challenge hypothesis]] which states that testosterone would increase during puberty, thus facilitating reproductive and competitive behavior which would include aggression.<ref name=":0" /> It is therefore the challenge of competition among males of the species that facilitates aggression and violence.<ref name=":0" /> Studies conducted have found direct correlation between testosterone and dominance, especially among the most violent criminals in prison who had the highest testosterone levels.<ref name=":0" /> The same research also found fathers (those outside competitive environments) had the lowest testosterone levels compared to other males.<ref name=":0" />
 
The second theory is similar and is known as "evolutionary neuroandrogenic (ENA) theory of male aggression".<ref name = "Ellis_2015">{{cite journal | vauthors = Ellis L, Hoskin AW |title = The evolutionary neuroandrogenic theory of criminal behavior expanded | url = https://www.researchgate.net/publication/276151720 | journal = Aggression and Violent Behavior | pages = 61–74 | volume = 24 | doi = 10.1016/j.avb.2015.05.002 | year = 2015 }}</ref><ref>{{cite journal | vauthors = Hoskin AW, Ellis L | title = Fetal Testosterone and Criminality: Test of Evolutionary Neuroandrogenic Theory | url = https://www.researchgate.net/publication/270007761 | journal = Criminology | pages = 54–73|volume = 53 | issue = 1 | doi = 10.1111/1745-9125.12056 | year = 2015 }}</ref> Testosterone and other androgens have evolved to masculinize a brain in order to be competitive even to the point of risking harm to the person and others. By doing so, individuals with masculinized brains as a result of pre-natal and adult life testosterone and androgens enhance their resource acquiring abilities in order to survive, attract and copulate with mates as much as possible.<ref name = "Ellis_2015" /> The masculinization of the brain is not just mediated by testosterone levels at the adult stage, but also testosterone exposure in the womb as a fetus. Higher pre-natal testosterone indicated by a low [[digit ratio]] as well as adult testosterone levels increased risk of fouls or aggression among male players in a soccer game.<ref>{{cite journal | vauthors = Perciavalle V, Di Corrado D, Petralia MC, Gurrisi L, Massimino S, Coco M | title = The second-to-fourth digit ratio correlates with aggressive behavior in professional soccer players | journal = Molecular Medicine Reports | volume = 7 | issue = 6 | pages = 1733–38 | date = Jun 2013 | pmid = 23588344 | pmc = 3694562 | doi = 10.3892/mmr.2013.1426 }}</ref> Studies have also found higher pre-natal testosterone or lower digit ratio to be correlated with higher aggression in males.<ref name="Bailey & Hurd 2005">{{cite journal | vauthors = Bailey AA, Hurd PL | title = Finger length ratio (2D:4D) correlates with physical aggression in men but not in women | journal = Biological Psychology | volume = 68 | issue = 3 | pages = 215–22 | date = Mar 2005 | pmid = 15620791 | doi = 10.1016/j.biopsycho.2004.05.001 | lay-url = http://www.livescience.com/193-finger-length-predicts-aggression-men.html | laydate = 2 March 2005 | laysource = [[LiveScience]] }}</ref><ref>{{cite journal | vauthors = Benderlioglu Z, Nelson RJ | title = Digit length ratios predict reactive aggression in women, but not in men | journal = Hormones and Behavior | volume = 46 | issue = 5 | pages = 558–64 | date = Dec 2004 | pmid = 15555497 | doi = 10.1016/j.yhbeh.2004.06.004 }}</ref><ref>{{cite journal | vauthors = Liu J, Portnoy J, Raine A | title = Association between a marker for prenatal testosterone exposure and externalizing behavior problems in children | journal = Development and Psychopathology | volume = 24 | issue = 3 | pages = 771–82 | date = Aug 2012 | pmid = 22781854 | pmc = 4247331 | doi = 10.1017/S0954579412000363 }}</ref><ref>{{cite journal | vauthors = Butovskaya M, Burkova V, Karelin D, Fink B | title = Digit ratio (2D:4D), aggression, and dominance in the Hadza and the Datoga of Tanzania | journal = American Journal of Human Biology | volume = 27 | issue = 5 | pages = 620–27 | date = 2015-10-01 | pmid = 25824265 | doi = 10.1002/ajhb.22718 }}</ref><ref>{{cite journal | vauthors = Joyce CW, Kelly JC, Chan JC, Colgan G, O'Briain D, Mc Cabe JP, Curtin W | title = Second to fourth digit ratio confirms aggressive tendencies in patients with boxers fractures | journal = Injury | volume = 44 | issue = 11 | pages = 1636–39 | date = Nov 2013 | pmid = 23972912 | doi = 10.1016/j.injury.2013.07.018 }}</ref>
 
The rise in testosterone levels during competition predicted aggression in males but not in females.<ref>{{cite journal | vauthors = Carré JM, Olmstead NA | title = Social neuroendocrinology of human aggression: examining the role of competition-induced testosterone dynamics | journal = Neuroscience | volume = 286 | pages = 171–86 | date = Feb 2015 | pmid = 25463514 | doi = 10.1016/j.neuroscience.2014.11.029 | url = http://carrelab.nipissingu.ca/wp-content/uploads/sites/32/2014/10/Carre-Olmstead-2015.pdf }}</ref> Subjects who interacted with hand guns and an experimental game showed rise in testosterone and aggression.<ref>{{cite journal | vauthors = Klinesmith J, Kasser T, McAndrew FT | title = Guns, testosterone, and aggression: an experimental test of a mediational hypothesis | journal = Psychological Science | volume = 17 | issue = 7 | pages = 568–71 | date = Jul 2006 | pmid = 16866740 | doi = 10.1111/j.1467-9280.2006.01745.x }}</ref> Natural selection might have evolved males to be more sensitive to competitive and status challenge situations and that the interacting roles of testosterone are the essential ingredient for aggressive behaviour in these situations.<ref>{{Cite journal|url = http://faculty.knox.edu/fmcandre/avb_506.pdf|title = The Interacting Roles of Testosterone and Challenges to Status in Human Male Aggression|last = Mcandrew|first = Francis T | name-list-format = vanc | date = 2009|journal = Aggression and Violent Behavior|doi = 10.1016/j.avb.2009.04.006|pmid = |access-date = |volume=14 |issue = 5|pages=330–335}}</ref> Testosterone produces aggression by activating subcortical areas in the brain, which may also be inhibited or suppressed by social norms or familial situations while still manifesting in diverse intensities and ways through thoughts, anger, verbal aggression, competition, dominance and physical violence.<ref>{{cite journal | vauthors = Batrinos ML | title = Testosterone and aggressive behavior in man | journal = International Journal of Endocrinology and Metabolism | volume = 10 | issue = 3 | pages = 563–68 | date = 2012-01-01 | pmid = 23843821 | pmc = 3693622 | doi = 10.5812/ijem.3661 }}</ref> Testosterone mediates attraction to cruel and violent cues in men by promoting extended viewing of violent stimuli.<ref>{{cite journal | vauthors = Weierstall R, Moran J, Giebel G, Elbert T | title = Testosterone reactivity and identification with a perpetrator or a victim in a story are associated with attraction to violence-related cues | journal = International Journal of Law and Psychiatry | volume = 37 | issue = 3 | pages = 304–12 | date = 2014-05-01 | pmid = 24367977 | doi = 10.1016/j.ijlp.2013.11.016 | url = http://nbn-resolving.de/urn:nbn:de:bsz:352-0-269427 }}</ref> Testosterone specific structural brain characteristic can predict aggressive behaviour in individuals.<ref>{{cite journal | vauthors = Nguyen TV, McCracken JT, Albaugh MD, Botteron KN, Hudziak JJ, Ducharme S | title = A testosterone-related structural brain phenotype predicts aggressive behavior from childhood to adulthood | journal = Psychoneuroendocrinology | volume = 63 | pages = 109–18 | date = Jan 2016 | pmid = 26431805 | pmc = 4695305 | doi = 10.1016/j.psyneuen.2015.09.021 }}</ref>
 
Testosterone might encourage fair behavior. For one study, subjects took part in a behavioral experiment where the distribution of a real amount of money was decided. The rules allowed both fair and unfair offers. The negotiating partner could subsequently accept or decline the offer. The fairer the offer, the less probable a refusal by the negotiating partner. If no agreement was reached, neither party earned anything. Test subjects with an artificially enhanced testosterone level generally made better, fairer offers than those who received placebos, thus reducing the risk of a rejection of their offer to a minimum. Two later studies have empirically confirmed these results.<ref name="pmid19997098">{{cite journal | vauthors = Eisenegger C, Naef M, Snozzi R, Heinrichs M, Fehr E | title = Prejudice and truth about the effect of testosterone on human bargaining behaviour | journal = Nature | volume = 463 | issue = 7279 | pages = 356–59 | year = 2010 | pmid = 19997098 | doi = 10.1038/nature08711 | bibcode = 2010Natur.463..356E }}</ref><ref>{{cite journal | vauthors = van Honk J, Montoya ER, Bos PA, van Vugt M, Terburg D | title = New evidence on testosterone and cooperation | journal = Nature | volume = 485 | issue = 7399 | pages = E4–5; discussion E5–6 | date = May 2012 | pmid = 22622587 | doi = 10.1038/nature11136 | bibcode = 2012Natur.485E...4V }}</ref><ref>{{cite journal | vauthors = Eisenegger C, Naef M, Snozzi R, Heinrichs M, Fehr E | year = 2012 | title = Eisenegger et al. reply| journal = Nature | volume = 485 | issue = 7399| pages = E5–E6 | doi = 10.1038/nature11137 | bibcode = 2012Natur.485E...5E }}</ref> However men with high testosterone were significantly 27% less generous in an ultimatum game.<ref>{{cite journal | vauthors = Zak PJ, Kurzban R, Ahmadi S, Swerdloff RS, Park J, Efremidze L, Redwine K, Morgan K, Matzner W | title = Testosterone administration decreases generosity in the ultimatum game | journal = PLoS ONE | volume = 4 | issue = 12 | page = e8330 | date = 2009-01-01 | pmid = 20016825 | pmc = 2789942 | doi = 10.1371/journal.pone.0008330 | bibcode = 2009PLoSO...4.8330Z }}</ref> The Annual NY Academy of Sciences has also found anabolic steroid use (which increases testosterone) to be higher in teenagers, and this was associated with increased violence.<ref>{{cite journal | vauthors = McGinnis MY | title = Anabolic androgenic steroids and aggression: studies using animal models | journal = Annals of the New York Academy of Sciences | volume = 1036 | pages = 399–415 | date = Dec 2004 | pmid = 15817752 | doi = 10.1196/annals.1330.024 | bibcode = 2004NYASA1036..399M }}</ref> Studies have also found administered testosterone to increase verbal aggression and anger in some participants.<ref>{{cite journal | vauthors = von der PB, Sarkola T, Seppa K, Eriksson CJ | title = Testosterone, 5 alpha-dihydrotestosterone and cortisol in men with and without alcohol-related aggression | journal = Journal of Studies on Alcohol | volume = 63 | issue = 5 | pages = 518–26 | date = Sep 2002 | pmid = 12380846 | doi=10.15288/jsa.2002.63.518}}</ref>
 
A few studies indicate that the testosterone derivative [[estradiol]] (one form of [[estrogen]]) might play an important role in male aggression.<ref name="isbn0-12-373612-9"/><ref>Goldman D, Lappalainen J, Ozaki N. Direct analysis of candidate genes in impulsive disorders. In: Bock G, Goode J, eds. Genetics of Criminal and Antisocial Behaviour. Ciba Foundation Symposium 194. Chichester: John Wiley & Sons; 1996.</ref><ref>{{cite journal | vauthors = Coccaro E | year = 1996 | title = Neurotransmitter correlates of impulsive aggression in humans. In: Ferris C, Grisso T, eds. Understanding Aggressive Behaviour inn Children | journal = Annals of the New York Academy of Sciences | volume = 794 | issue = 1| pages = 82–89 | doi=10.1111/j.1749-6632.1996.tb32511.x| pmid = 8853594 | bibcode = 1996NYASA.794...82C }}</ref><ref name="pmid9253313">{{cite journal | vauthors = Finkelstein JW, Susman EJ, Chinchilli VM, Kunselman SJ, D'Arcangelo MR, Schwab J, Demers LM, Liben LS, Lookingbill G, Kulin HE | title = Estrogen or testosterone increases self-reported aggressive behaviors in hypogonadal adolescents | journal = Journal of Clinical Endocrinology and Metabolism | volume = 82 | issue = 8 | pages = 2433–38 | year = 1997 | pmid = 9253313 | doi = 10.1210/jcem.82.8.4165 }}</ref> Estradiol is known to correlate with aggression in male mice.<ref name="pmid18280561">{{cite journal | vauthors = Soma KK, Scotti MA, Newman AE, Charlier TD, Demas GE | title = Novel mechanisms for neuroendocrine regulation of aggression | journal = Frontiers in Neuroendocrinology | volume = 29 | issue = 4 | pages = 476–89 | date = Oct 2008 | pmid = 18280561 | doi = 10.1016/j.yfrne.2007.12.003 }}</ref> Moreover, the conversion of testosterone to estradiol regulates male aggression in [[Old World sparrow|sparrows]] during breeding season.<ref name="pmid11016791">{{cite journal | vauthors = Soma KK, Sullivan KA, Tramontin AD, Saldanha CJ, Schlinger BA, Wingfield JC | title = Acute and chronic effects of an aromatase inhibitor on territorial aggression in breeding and nonbreeding male song sparrows | journal = Journal of Comparative Physiology A | volume = 186 | issue = 7–8 | pages = 759–69 | year = 2000 | pmid = 11016791 | doi = 10.1007/s003590000129 }}</ref> Rats who were given anabolic steroids that increase testosterone were also more physically aggressive to provocation as a result of "threat sensitivity".<ref>{{cite journal | vauthors = McGinnis MY, Lumia AR, Breuer ME, Possidente B | title = Physical provocation potentiates aggression in male rats receiving anabolic androgenic steroids | journal = Hormones and Behavior | volume = 41 | issue = 1 | pages = 101–10 | date = Feb 2002 | pmid = 11863388 | doi = 10.1006/hbeh.2001.1742 }}</ref>
 
===Brain===
The brain is also affected by this sexual differentiation;<ref name="pmid19403051"/> the [[enzyme]] [[aromatase]] converts testosterone into [[estradiol]] that is responsible for [[masculinization]] of the brain in male mice. In humans, masculinization of the fetal brain appears, by observation of gender preference in patients with [[congenital disease]]s of androgen formation or androgen receptor function, to be associated with functional androgen receptors.<ref name="pmid11534997">{{cite journal | vauthors = Wilson JD | title = Androgens, androgen receptors, and male gender role behavior | journal = Hormones and Behavior | volume = 40 | issue = 2 | pages = 358–66 | date = Sep 2001 | pmid = 11534997 | doi = 10.1006/hbeh.2001.1684 | url = https://semanticscholar.org/paper/75bb071beb950f66cd032b9d5a9633c255f80660 }}</ref>
 
There are some [[Neuroscience of sex differences|differences between a male and female brain]] (possibly the result of different testosterone levels), one of them being size: the male human brain is, on average, larger.<ref name="pmid17544382">{{cite journal | vauthors = Cosgrove KP, Mazure CM, Staley JK | title = Evolving knowledge of sex differences in brain structure, function, and chemistry | journal = Biological Psychiatry | volume = 62 | issue = 8 | pages = 847–55 | date = Oct 2007 | pmid = 17544382 | pmc = 2711771 | doi = 10.1016/j.biopsych.2007.03.001 }}</ref> Men were found to have a total [[myelin|myelinated fiber]] length of 176&nbsp;000&nbsp;km at the age of 20, whereas in women the total length was 149&nbsp;000&nbsp;km (approx. 15% less).<ref name="pmid12794739">{{cite journal | vauthors = Marner L, Nyengaard JR, Tang Y, Pakkenberg B | title = Marked loss of myelinated nerve fibers in the human brain with age | journal = The Journal of Comparative Neurology | volume = 462 | issue = 2 | pages = 144–52 | date = Jul 2003 | pmid = 12794739 | doi = 10.1002/cne.10714 }}</ref>
 
No immediate short term effects on mood or behavior were found from the administration of [[wiktionary:supraphysiological|supraphysiologic]] doses of testosterone for 10 weeks on 43 healthy men.<ref name="pmid8637535">{{cite journal | vauthors = Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi A, Casaburi R | title = The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men | journal = The New England Journal of Medicine | volume = 335 | issue = 1 | pages = 1–7 | date = Jul 1996 | pmid = 8637535 | doi = 10.1056/NEJM199607043350101 }}</ref> A correlation between testosterone and risk tolerance in career choice exists among women.<ref name="pmid19706398"/><ref>{{cite web | url = https://www.npr.org/templates/story/story.php?storyId=112334459 | title = Testosterone Affects Some Women's Career Choices | date = August 28, 2009 | publisher = NPR}}</ref>
 
Attention, memory, and spatial ability are key cognitive functions affected by testosterone in humans. Preliminary evidence suggests that low testosterone levels may be a risk factor for cognitive decline and possibly for [[dementia]] of the Alzheimer's type,<ref name="pmid16785599">{{cite journal | vauthors = Pike CJ, Rosario ER, Nguyen TV | title = Androgens, aging, and Alzheimer's disease | journal = Endocrine | volume = 29 | issue = 2 | pages = 233–41 | date = Apr 2006 | pmid = 16785599 | doi = 10.1385/ENDO:29:2:233 }}</ref><ref name="pmid15383512">{{cite journal | vauthors = Rosario ER, Chang L, Stanczyk FZ, Pike CJ | title = Age-related testosterone depletion and the development of Alzheimer disease | journal = JAMA | volume = 292 | issue = 12 | pages = 1431–32 | date = Sep 2004 | pmid = 15383512 | doi = 10.1001/jama.292.12.1431-b }}</ref><ref name="pmid15582279">{{cite journal | vauthors = Hogervorst E, Bandelow S, Combrinck M, Smith AD | title = Low free testosterone is an independent risk factor for Alzheimer's disease | journal = Experimental Gerontology | volume = 39 | issue = 11–12 | pages = 1633–39 | year = 2004 | pmid = 15582279 | doi = 10.1016/j.exger.2004.06.019 }}</ref><ref name="pmid14745052">{{cite journal | vauthors = Moffat SD, Zonderman AB, Metter EJ, Kawas C, Blackman MR, Harman SM, Resnick SM | title = Free testosterone and risk for Alzheimer disease in older men | journal = Neurology | volume = 62 | issue = 2 | pages = 188–93 | date = Jan 2004 | pmid = 14745052 | doi = 10.1212/WNL.62.2.188 }}</ref> a key argument in [[life extension]] medicine for the use of testosterone in anti-aging therapies. Much of the literature, however, suggests a curvilinear or even quadratic relationship between spatial performance and circulating testosterone,<ref name="pmid8817730">{{cite journal | vauthors = Moffat SD, Hampson E | title = A curvilinear relationship between testosterone and spatial cognition in humans: possible influence of hand preference | journal = Psychoneuroendocrinology | volume = 21 | issue = 3 | pages = 323–37 | date = Apr 1996 | pmid = 8817730 | doi = 10.1016/0306-4530(95)00051-8 }}</ref> where both hypo- and hypersecretion (deficient- and excessive-secretion) of circulating androgens have negative effects on cognition.
 
===Immune system and inflammation===
Testosteone deficiency is associated with an increased risk of [[metabolic syndrome]], [[cardiovascular disease]] and [[Mortality rate|mortality]], which are also sequelae of chronic [[inflammation]].<ref name="Bianchi_2018">{{cite journal |last1=Bianchi |first1=Vittorio Emanuele |title=The Anti-Inflammatory Effects of Testosterone |journal=Journal of the Endocrine Society |date=January 2019 |volume=3 |issue=1 |pages=91–107 |doi=10.1210/js.2018-00186 |pmid=30582096|pmc=6299269 }}</ref> Testosterone plasma concentration inversely correlates to multiple [[biomarker]]s of inflammation including [[C-reactive protein|CRP]], [[interleukin 1 beta]], [[interleukin 6]], [[TNF alpha]] and [[endotoxin]] concentration, as well as [[leukocyte]] count.<ref name="Bianchi_2018"/> As demonstrated by a [[meta-analysis]], substitution therapy with testosterone results in a significant reduction of inflammatory markers.<ref name="Bianchi_2018"/> These effects are mediated by different mechanisms with synergistic action.<ref name="Bianchi_2018"/> In androgen-deficient men with concomitant [[autoimmune thyroiditis]], substitution therapy with testosterone leads to a decrease in [[thyroid autoantibody]] titres and an increase in [[thyroid's secretory capacity]] (SPINA-GT).<ref>{{cite journal |last1=Krysiak |first1=Robert |last2=Kowalcze |first2=Karolina |last3=Okopień |first3=Bogusław |title=The effect of testosterone on thyroid autoimmunity in euthyroid men with Hashimoto's thyroiditis and low testosterone levels |journal=Journal of Clinical Pharmacy and Therapeutics |volume=44 |issue=5 |pages=742–749 |date=10 June 2019 |doi=10.1111/jcpt.12987 |pmid=31183891}}</ref>
 
==Medical use==
{{Main|Testosterone (medication)}}
 
Testosterone is used as a medication for the treatment of [[hypogonadism|males with too little or no natural testosterone production]], certain forms of [[breast cancer]],<ref name=AHFS2016>{{cite web|title=Testosterone|url=https://www.drugs.com/monograph/testosterone.html|website=Drugs.com|publisher=American Society of Health-System Pharmacists|accessdate=3 September 2016|date=December 4, 2015}}</ref> and gender dysphoria in transgender men. This is known as [[hormone replacement therapy]] (HRT) or testosterone replacement therapy (TRT), which maintains serum testosterone levels in the normal range. [[andropause|Decline of testosterone production with age]] has led to interest in [[androgen replacement therapy]].<ref name="pmid16985841">{{cite journal | vauthors = Myers JB, Meacham RB | title = Androgen replacement therapy in the aging male | journal = Reviews in Urology | volume = 5 | issue = 4 | pages = 216–26 | year = 2003 | pmid = 16985841 | pmc = 1508369 | doi = }}</ref> It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful.<ref name=FDA2015>{{cite web |author=Staff |title=Testosterone Products: Drug Safety Communication – FDA Cautions About Using Testosterone Products for Low Testosterone Due to Aging; Requires Labeling Change to Inform of Possible Increased Risk of Heart Attack And Stroke |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-cautions-about-using-testosterone-products-low-testosterone-due |date=3 March 2015 |work=[[FDA]] |accessdate=5 March 2015 }}</ref>
 
Testosterone is included in the [[WHO Model List of Essential Medicines|World Health Organization's list of essential medicines]], which are the most important medications needed in a basic [[health system]].<ref name=WHO2015E>{{cite web |url=http://www.who.int/medicines/publications/essentialmedicines/EML2015_8-May-15.pdf |title=19th WHO Model List of Essential Medicines (April 2015) |date=April 2015 |accessdate=May 10, 2015 |publisher=WHO }}</ref> It is available as a [[generic medication]].<ref name="AHFS2016"/> The price depends on the form of testosterone used.<ref name=Ric2015>{{cite book | last1 = Hamilton | first1 = Richart | name-list-format = vanc | title = Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning | isbn = 978-1-284-05756-0 | page=197 }}</ref> It can be administered as a cream or [[transdermal patch]] that is applied to the skin, by [[intramuscular injection|injection into a muscle]], as a tablet that is [[Buccal administration|placed in the cheek]], or by ingestion.<ref name=AHFS2016/>
 
Common [[side effect]]s from testosterone medication include [[acne]], [[swelling (medical)|swelling]], and [[gynecomastia|breast enlargement in males]].<ref name=AHFS2016/> Serious side effects may include [[liver toxicity]], [[heart disease]], and behavioral changes.<ref name=AHFS2016/> Women and children who are exposed may develop [[virilization]].<ref name=AHFS2016/> It is recommended that individuals with [[prostate cancer]] not use the medication.<ref name=AHFS2016/> It can cause harm if used during [[pregnancy]] or [[breastfeeding]].<ref name=AHFS2016/>
 
==Biological activity==
 
===Steroid hormone activity===
The effects of testosterone in humans and other [[vertebrates]] occur by way of multiple mechanisms: by activation of the [[androgen receptor]] (directly or as DHT), and by conversion to [[estradiol]] and activation of certain [[estrogen receptor]]s.<ref name="pmid18406296">{{cite journal | vauthors = Hiipakka RA, Liao S | title = Molecular mechanism of androgen action | journal = Trends in Endocrinology and Metabolism | volume = 9 | issue = 8 | pages = 317–24 | date = Oct 1998 | pmid = 18406296 | doi = 10.1016/S1043-2760(98)00081-2 }}</ref><ref name="pmid11511858">{{cite journal | vauthors = McPhaul MJ, Young M | title = Complexities of androgen action | journal = Journal of the American Academy of Dermatology | volume = 45 | issue = 3 Suppl | pages = S87–94 | date = Sep 2001 | pmid = 11511858 | doi = 10.1067/mjd.2001.117429 }}</ref> Androgens such as testosterone have also been found to bind to and activate [[membrane androgen receptor]]s.<ref name="pmid19931639">{{cite journal | vauthors = Bennett NC, Gardiner RA, Hooper JD, Johnson DW, Gobe GC | title = Molecular cell biology of androgen receptor signalling | journal = Int. J. Biochem. Cell Biol. | volume = 42 | issue = 6 | pages = 813–27 | year = 2010 | pmid = 19931639 | doi = 10.1016/j.biocel.2009.11.013 }}</ref><ref name="pmid25257522">{{cite journal | vauthors = Wang C, Liu Y, Cao JM | title = G protein-coupled receptors: extranuclear mediators for the non-genomic actions of steroids | journal = Int J Mol Sci | volume = 15 | issue = 9 | pages = 15412–25 | year = 2014 | pmid = 25257522 | pmc = 4200746 | doi = 10.3390/ijms150915412 }}</ref><ref name="pmid23746222">{{cite journal | vauthors = Lang F, Alevizopoulos K, Stournaras C | title = Targeting membrane androgen receptors in tumors | journal = Expert Opin. Ther. Targets | volume = 17 | issue = 8 | pages = 951–63 | year = 2013 | pmid = 23746222 | doi = 10.1517/14728222.2013.806491 }}</ref>
 
Free testosterone (T) is transported into the [[cytoplasm]] of target [[Tissue (biology)|tissue]] [[Cell (biology)|cells]], where it can bind to the [[androgen receptor]], or can be reduced to 5α-[[dihydrotestosterone]] (DHT) by the cytoplasmic enzyme [[5α-reductase]]. DHT binds to the same androgen receptor even more strongly than testosterone, so that its androgenic potency is about 5 times that of T.<ref name="pmid3762019">{{cite journal | vauthors = Breiner M, Romalo G, Schweikert HU | title = Inhibition of androgen receptor binding by natural and synthetic steroids in cultured human genital skin fibroblasts | journal = Klinische Wochenschrift | volume = 64 | issue = 16 | pages = 732–37 | date = Aug 1986 | pmid = 3762019 | doi = 10.1007/BF01734339 }}</ref> The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the [[cell nucleus]] and bind directly to specific [[nucleotide]] sequences of the [[chromosome|chromosomal]] DNA. The areas of binding are called [[hormone response element]]s (HREs), and influence transcriptional activity of certain [[gene]]s, producing the androgen effects.
 
Androgen receptors occur in many different vertebrate body system tissues, and both males and females respond similarly to similar levels. Greatly differing amounts of testosterone prenatally, at puberty, and throughout life account for a share of [[sexual differentiation|biological differences]] between males and females.
 
The bones and the brain are two important tissues in humans where the primary effect of testosterone is by way of [[aromatization]] to [[estradiol]]. In the bones, estradiol accelerates ossification of cartilage into bone, leading to closure of the [[epiphysis|epiphyses]] and conclusion of growth. In the central nervous system, testosterone is aromatized to estradiol. Estradiol rather than testosterone serves as the most important feedback signal to the hypothalamus (especially affecting [[luteinizing hormone|LH]] secretion).<ref>{{cite book | vauthors = Kelly MJ, Qiu J, Rønnekleiv OK | title = Estrogen signaling in the hypothalamus | volume = 71 | pages = 123–45 | date = 2005-01-01 | pmid = 16112267 | doi = 10.1016/S0083-6729(05)71005-0 | series = Vitamins & Hormones | isbn = 9780127098715 }}</ref> In many [[mammal]]s, prenatal or perinatal "masculinization" of the [[sexual dimorphism|sexually dimorphic]] areas of the brain by estradiol derived from testosterone programs later male sexual behavior.<ref name="pmid18195084">{{cite journal | vauthors = McCarthy MM | title = Estradiol and the developing brain | journal = Physiological Reviews | volume = 88 | issue = 1 | pages = 91–124 | year = 2008 | pmid = 18195084 | pmc = 2754262 | doi = 10.1152/physrev.00010.2007 }}</ref>
 
===Neurosteroid activity===
Testosterone, via its [[active metabolite]] [[3α-androstanediol]], is a potent [[positive allosteric modulator]] of the [[GABAA receptor|GABA<sub>A</sub> receptor]].<ref name="KohtzFrye2012">{{cite book | vauthors = Kohtz AS, Frye CA | title = Dissociating behavioral, autonomic, and neuroendocrine effects of androgen steroids in animal models | journal = [[Methods in Molecular Biology]] | volume = 829 | issue = | pages = 397–431 | year = 2012 | pmid = 22231829 | doi = 10.1007/978-1-61779-458-2_26 | isbn = 978-1-61779-457-5 }}</ref>
 
Testosterone has been found to act as an [[receptor antagonist|antagonist]] of the [[TrkA]] and [[p75NTR|p75<sup>NTR</sup>]], [[receptor (biochemistry)|receptor]]s for the [[neurotrophin]] [[nerve growth factor]] (NGF), with high [[affinity (pharmacology)|affinity]] (around 5&nbsp;nM).<ref name="pmid26908835">{{cite journal | vauthors = Prough RA, Clark BJ, Klinge CM | title = Novel mechanisms for DHEA action | journal = J. Mol. Endocrinol. | volume = 56 | issue = 3 | pages = R139–55 | year = 2016 | pmid = 26908835 | doi = 10.1530/JME-16-0013 | url = }}</ref><ref name="pmid21541365">{{cite journal | vauthors = Lazaridis I, Charalampopoulos I, Alexaki VI, Avlonitis N, Pediaditakis I, Efstathopoulos P, Calogeropoulou T, Castanas E, Gravanis A | title = Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis | journal = PLoS Biol. | volume = 9 | issue = 4 | pages = e1001051 | year = 2011 | pmid = 21541365 | pmc = 3082517 | doi = 10.1371/journal.pbio.1001051 | url = }}</ref><ref name="pmid23074265">{{cite journal | vauthors = Gravanis A, Calogeropoulou T, Panoutsakopoulou V, Thermos K, Neophytou C, Charalampopoulos I | title = Neurosteroids and microneurotrophins signal through NGF receptors to induce prosurvival signaling in neuronal cells | journal = Sci Signal | volume = 5 | issue = 246 | pages = pt8 | year = 2012 | pmid = 23074265 | doi = 10.1126/scisignal.2003387 | url = }}</ref> In contrast to testosterone, DHEA and [[DHEA sulfate]] have been found to act as high-affinity [[agonist]]s of these receptors.<ref name="pmid26908835" /><ref name="pmid21541365" /><ref name="pmid23074265" />
 
Testosterone is an [[receptor antagonist|antagonist]] of the [[sigma receptor|sigma]] [[sigma-1 receptor|σ<sub>1</sub> receptor]] (K<sub>i</sub> = 1,014 or 201&nbsp;nM).<ref name="AlbayrakHashimoto2017">{{cite book | vauthors = Albayrak Y, Hashimoto K | title = Sigma-1 Receptor Agonists and Their Clinical Implications in Neuropsychiatric Disorders | journal = Advances in Experimental Medicine and Biology | volume = 964 | pages = 153–161 | year = 2017 | pmid = 28315270 | doi = 10.1007/978-3-319-50174-1_11 | isbn = 978-3-319-50172-7 }}</ref> However, the concentrations of testosterone required for binding the receptor are far above even total circulating concentrations of testosterone in adult males (which range between 10 and 35&nbsp;nM).<ref name="Regitz-Zagrosek2012">{{cite book| first = Vera | last = Regitz-Zagrosek | name-list-format = vanc |title=Sex and Gender Differences in Pharmacology|url=https://books.google.com/books?id=J3VxihGDh9wC&pg=PA245|date=2 October 2012|publisher=Springer Science & Business Media|isbn=978-3-642-30725-6|pages=245–}}</ref>
 
==Biochemistry==
[[File:Steroidogenesis.svg|thumb|500px|Human [[steroidogenesis]], showing testosterone near bottom.<ref name="HäggströmRichfield2014">{{cite journal | vauthors = Häggström M, Richfield D |year=2014|title=Diagram of the pathways of human steroidogenesis|journal=WikiJournal of Medicine|volume=1|issue=1|doi=10.15347/wjm/2014.005}}</ref>]]
 
===Biosynthesis===
Like other [[steroid]] hormones, testosterone is derived from [[cholesterol]] (see figure).<ref name="pmid1307739">{{cite journal | vauthors = Waterman MR, Keeney DS | title = Genes involved in androgen biosynthesis and the male phenotype | journal = Hormone Research | volume = 38 | issue = 5–6 | pages = 217–21 | year = 1992 | pmid = 1307739 | doi = 10.1159/000182546 }}</ref> The first step in the [[biosynthesis]] involves the oxidative cleavage of the side-chain of cholesterol by [[cholesterol side-chain cleavage enzyme]] (P450scc, CYP11A1), a [[mitochondrion|mitochondrial]] [[cytochrome P450]] oxidase with the loss of six carbon atoms to give [[pregnenolone]]. In the next step, two additional carbon atoms are removed by the [[CYP17A1]] (17α-hydroxylase/17,20-lyase) enzyme in the [[endoplasmic reticulum]] to yield a variety of C<sub>19</sub> steroids.<ref name="pmid3535074">{{cite journal | vauthors = Zuber MX, Simpson ER, Waterman MR | title = Expression of bovine 17 alpha-hydroxylase cytochrome P-450 cDNA in nonsteroidogenic (COS 1) cells | journal = Science | volume = 234 | issue = 4781 | pages = 1258–61 | date = Dec 1986 | pmid = 3535074 | doi = 10.1126/science.3535074 | bibcode = 1986Sci...234.1258Z }}</ref> In addition, the 3β-hydroxyl group is oxidized by [[3β-hydroxysteroid dehydrogenase]] to produce [[androstenedione]]. In the final and rate limiting step, the C17 keto group androstenedione is reduced by [[17β-hydroxysteroid dehydrogenase]] to yield testosterone.
 
The largest amounts of testosterone (>95%) are produced by the [[testis|testes]] in men,<ref name="Mooradian_ 1987"/> while the [[adrenal gland]]s account for most of the remainder. Testosterone is also synthesized in far smaller total quantities in women by the adrenal glands, [[theca of follicle|thecal cells]] of the [[ovary|ovaries]], and, during [[pregnancy]], by the [[placenta]].<ref name="pmid15507105">{{cite journal | vauthors = Zouboulis CC, Degitz K | title = Androgen action on human skin – from basic research to clinical significance | journal = Experimental Dermatology | volume = 13 Suppl 4 | issue = s4 | pages = 5–10 | year = 2004 | pmid = 15507105 | doi = 10.1111/j.1600-0625.2004.00255.x }}</ref> In the [[testes]], testosterone is produced by the [[Leydig cell]]s.<ref name="pmid58744">{{cite journal | vauthors = Brooks RV | title = Androgens | journal = Clinics in Endocrinology and Metabolism | volume = 4 | issue = 3 | pages = 503–20 | date = Nov 1975 | pmid = 58744 | doi = 10.1016/S0300-595X(75)80045-4 }}</ref> The male generative glands also contain [[Sertoli cell]]s, which require testosterone for [[spermatogenesis]]. Like most hormones, testosterone is supplied to target tissues in the blood where much of it is transported bound to a specific [[plasma protein]], [[sex hormone-binding globulin]] (SHBG).
 
====Regulation====
[[File:Hypothalamus pituitary testicles axis.png|thumb|right|Hypothalamic–pituitary–testicular axis]]
 
In males, testosterone is synthesized primarily in [[Leydig cells]]. The number of Leydig cells in turn is regulated by [[luteinizing hormone]] (LH) and [[follicle-stimulating hormone]] (FSH). In addition, the amount of testosterone produced by existing Leydig cells is under the control of LH, which regulates the expression of [[17β-hydroxysteroid dehydrogenase]].<ref name="isbn0-9627422-7-9">{{cite book | vauthors = Payne AH, O'Shaughnessy P |veditors=Payne AH, Hardy MP, Russell LD | title = Leydig Cell | edition = | publisher = Cache River Press | location = Vienna [Il] | year = 1996 | origyear = | pages = 260–85 | quote = | isbn = 978-0-9627422-7-9 | oclc = | doi = | chapter = Structure, function, and regulation of steroidogenic enzymes in the Leydig cell }}</ref>
 
The amount of testosterone synthesized is regulated by the [[hypothalamic–pituitary–gonadal axis|hypothalamic–pituitary–testicular axis]] (see figure to the right).<ref name="pmid1377467">{{cite journal | vauthors = Swerdloff RS, Wang C, Bhasin S | title = Developments in the control of testicular function | journal = Baillière's Clinical Endocrinology and Metabolism | volume = 6 | issue = 2 | pages = 451–83 | date = Apr 1992 | pmid = 1377467 | doi = 10.1016/S0950-351X(05)80158-2 }}</ref> When testosterone levels are low, gonadotropin-releasing hormone ([[gonadotropin-releasing hormone|GnRH]]) is released by the [[hypothalamus]], which in turn stimulates the [[pituitary gland]] to release FSH and LH. These latter two hormones stimulate the testis to synthesize testosterone. Finally, increasing levels of testosterone through a negative [[feedback]] loop act on the hypothalamus and pituitary to inhibit the release of GnRH and FSH/LH, respectively.
 
Factors affecting testosterone levels may include:
 
* Age: Testosterone levels gradually reduce as men age.<ref name="auto">{{cite book | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK216164/ | title = Testosterone and Aging: Clinical Research Directions. | chapter = Introduction | last3 = ((Institute of Medicine (US) Committee on Assessing the Need for Clinical Trials of Testosterone Replacement Therapy)) | first1 = Catharyn T. | last1 = Liverman | first2 = Dan G. | last2 = Blazer | name-list-format = vanc | date = January 1, 2004 | publisher = National Academies Press (US) | via = www.ncbi.nlm.nih.gov | isbn = 978-0-309-09063-6 | doi = 10.17226/10852 | pmid = 25009850 }}</ref><ref name="pmid24407185">{{cite journal | vauthors = Huhtaniemi I | title = Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment | journal = Asian Journal of Andrology | volume = 16 | issue = 2 | pages = 192–202 | year = 2014 | pmid = 24407185 | pmc = 3955328 | doi = 10.4103/1008-682X.122336 }}</ref> This effect is sometimes referred to as [[andropause]] or [[late-onset hypogonadism]].<ref name="pmid24793989">{{cite journal | vauthors = Huhtaniemi IT | title = Andropause--lessons from the European Male Ageing Study | journal = Annales d'Endocrinologie | volume = 75 | issue = 2 | pages = 128–31 | year = 2014 | pmid = 24793989 | doi = 10.1016/j.ando.2014.03.005 }}</ref>
* Exercise: Resistance training increases testosterone levels,<ref name="Vingren_2010">{{cite journal | vauthors = Vingren JL, Kraemer WJ, Ratamess NA, Anderson JM, Volek JS, Maresh CM | title = Testosterone physiology in resistance exercise and training: the up-stream regulatory elements | journal = Sports Medicine | volume = 40 | issue = 12 | pages = 1037–53 | year = 2010 | pmid = 21058750 | doi = 10.2165/11536910-000000000-00000 }}</ref> however, in older men, that increase can be avoided by protein ingestion.<ref name="pmid18455389">{{cite journal | vauthors = Hulmi JJ, Ahtiainen JP, Selänne H, Volek JS, Häkkinen K, Kovanen V, Mero AA | title = Androgen receptors and testosterone in men—effects of protein ingestion, resistance exercise and fiber type | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 110 | issue = 1–2 | pages = 130–37 | date = May 2008 | pmid = 18455389 | doi = 10.1016/j.jsbmb.2008.03.030 }}</ref> Endurance training in men may lead to lower testosterone levels.<ref name="pmid16268050">{{cite journal | vauthors = Hackney AC, Moore AW, Brownlee KK | title = Testosterone and endurance exercise: development of the "exercise-hypogonadal male condition" | journal = Acta Physiologica Hungarica | volume = 92 | issue = 2 | pages = 121–37 | year = 2005 | pmid = 16268050 | doi = 10.1556/APhysiol.92.2005.2.3 }}</ref>
* Nutrients: [[Vitamin A deficiency]] may lead to sub-optimal plasma testosterone levels.<ref name="pmid12141930">{{cite journal | vauthors = Livera G, Rouiller-Fabre V, Pairault C, Levacher C, Habert R | title = Regulation and perturbation of testicular functions by vitamin A | journal = Reproduction | volume = 124 | issue = 2 | pages = 173–80 | date = Aug 2002 | pmid = 12141930 | doi = 10.1530/rep.0.1240173 }}</ref> The secosteroid [[vitamin D]] in levels of 400–1000&nbsp;[[international unit|IU]]/d (10–25&nbsp;µg/d) raises testosterone levels.<ref name="pmid21154195">{{cite journal | vauthors = Pilz S, Frisch S, Koertke H, Kuhn J, Dreier J, Obermayer-Pietsch B, Wehr E, Zittermann A | title = Effect of vitamin D supplementation on testosterone levels in men | journal = Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Métabolisme | volume = 43 | issue = 3 | pages = 223–25 | date = Mar 2011 | pmid = 21154195 | doi = 10.1055/s-0030-1269854 }}</ref> [[Zinc deficiency]] lowers testosterone levels<ref name="pmid8875519">{{cite journal | vauthors = Prasad AS, Mantzoros CS, Beck FW, Hess JW, Brewer GJ | title = Zinc status and serum testosterone levels of healthy adults | journal = Nutrition | volume = 12 | issue = 5 | pages = 344–48 | date = May 1996 | pmid = 8875519 | doi = 10.1016/S0899-9007(96)80058-X | citeseerx = 10.1.1.551.4971 }}</ref> but over-supplementation has no effect on serum testosterone.<ref name="pmid17882141">{{cite journal | vauthors = Koehler K, Parr MK, Geyer H, Mester J, Schänzer W | title = Serum testosterone and urinary excretion of steroid hormone metabolites after administration of a high-dose zinc supplement | journal = European Journal of Clinical Nutrition | volume = 63 | issue = 1 | pages = 65–70 | date = Jan 2009 | pmid = 17882141 | doi = 10.1038/sj.ejcn.1602899 }}</ref>
* Weight loss: Reduction in weight may result in an increase in testosterone levels. Fat cells synthesize the enzyme aromatase, which converts testosterone, the male sex hormone, into estradiol, the female sex hormone.<ref name="pmid21849026">{{cite journal | vauthors = Håkonsen LB, Thulstrup AM, Aggerholm AS, Olsen J, Bonde JP, Andersen CY, Bungum M, Ernst EH, Hansen ML, Ernst EH, Ramlau-Hansen CH | title = Does weight loss improve semen quality and reproductive hormones? Results from a cohort of severely obese men | journal = Reproductive Health | volume = 8 | issue = 1 | page = 24 | year = 2011 | pmid = 21849026 | pmc = 3177768 | doi = 10.1186/1742-4755-8-24 }}</ref> However no clear association between [[body mass index]] and testosterone levels has been found.<ref name="pmid19889752">{{cite journal | vauthors = MacDonald AA, Herbison GP, Showell M, Farquhar CM | title = The impact of body mass index on semen parameters and reproductive hormones in human males: a systematic review with meta-analysis | journal = Human Reproduction Update | volume = 16 | issue = 3 | pages = 293–311 | year = 2010 | pmid = 19889752 | doi = 10.1093/humupd/dmp047 | url = }}</ref>
* Miscellaneous: ''Sleep'': ([[REM sleep]]) increases nocturnal testosterone levels.<ref name="pmid18519168">{{cite journal | vauthors = Andersen ML, Tufik S | title = The effects of testosterone on sleep and sleep-disordered breathing in men: its bidirectional interaction with erectile function | journal = Sleep Medicine Reviews | volume = 12 | issue = 5 | pages = 365–79 | date = Oct 2008 | pmid = 18519168 | doi = 10.1016/j.smrv.2007.12.003 }}</ref> ''Behavior'': Dominance challenges can, in some cases, stimulate increased testosterone release in men.<ref name="pmid10603287">{{cite journal | vauthors = Schultheiss OC, Campbell KL, McClelland DC | title = Implicit power motivation moderates men's testosterone responses to imagined and real dominance success | journal = Hormones and Behavior | volume = 36 | issue = 3 | pages = 234–41 | date = Dec 1999 | pmid = 10603287 | doi = 10.1006/hbeh.1999.1542 | url = https://semanticscholar.org/paper/82c6fd7dbf4a7681a161e6a7bdd5b1b1a7b211c0 }}</ref> ''Drugs'': Natural or man-made [[antiandrogens]] including [[spearmint]] tea reduce testosterone levels.<ref name="pmid17310494">{{cite journal | vauthors = Akdoğan M, Tamer MN, Cüre E, Cüre MC, Köroğlu BK, Delibaş N | title = Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism | journal = Phytotherapy Research | volume = 21 | issue = 5 | pages = 444–47 | date = May 2007 | pmid = 17310494 | doi = 10.1002/ptr.2074 }}</ref><ref name="pmid18804513">{{cite journal | vauthors = Kumar V, Kural MR, Pereira BM, Roy P | title = Spearmint induced hypothalamic oxidative stress and testicular anti-androgenicity in male rats - altered levels of gene expression, enzymes and hormones | journal = Food and Chemical Toxicology | volume = 46 | issue = 12 | pages = 3563–70 | date = Dec 2008 | pmid = 18804513 | doi = 10.1016/j.fct.2008.08.027 }}</ref><ref name="pmid19585478">{{cite journal | vauthors = Grant P | title = Spearmint herbal tea has significant anti-androgen effects in polycystic ovarian syndrome. A randomized controlled trial | journal = Phytotherapy Research | volume = 24 | issue = 2 | pages = 186–88 | date = Feb 2010 | pmid = 19585478 | doi = 10.1002/ptr.2900 }}</ref> [[Licorice]] can decrease the production of testosterone and this effect is greater in females.<ref>{{cite journal | vauthors = Armanini D, Fiore C, Mattarello MJ, Bielenberg J, Palermo M | title = History of the endocrine effects of licorice | journal = Experimental and Clinical Endocrinology & Diabetes | volume = 110 | issue = 6 | pages = 257–61 | date = Sep 2002 | pmid = 12373628 | doi = 10.1055/s-2002-34587 }}</ref>
 
===Distribution===
The [[plasma protein binding]] of testosterone is 98.0 to 98.5%, with 1.5 to 2.0% free or unbound.<ref name="NieschlagBehre2012" /> It is bound 65% to [[sex hormone-binding globulin]] (SHBG) and 33% bound weakly to [[human serum albumin|albumin]].<ref name="pmid4044776">{{cite journal | vauthors = Cumming DC, Wall SR | title = Non-sex hormone-binding globulin-bound testosterone as a marker for hyperandrogenism | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 61 | issue = 5 | pages = 873–6 | date = November 1985 | pmid = 4044776 | doi = 10.1210/jcem-61-5-873 }}</ref>
 
{| class="wikitable mw-collapsible mw-collapsed" style="text-align:left; margin-left:auto; margin-right:auto; border:none;"
|+ class="nowrap" | Plasma protein binding of testosterone and dihydrotestosterone
|-
! Compound !! Group !! Level (nM) !! Free (%) !! {{abbrlink|SHBG|Sex hormone-binding globulin}} (%) !! {{abbrlink|CBG|Corticosteroid-binding globulin}} (%) !! [[Human serum albumin|Albumin]] (%)
|-
| rowspan="5" | Testosterone || Adult men || 23.0 || 2.23 || 44.3 || 3.56 || 49.9
|-
| colspan="6" | Adult women
|-
| &nbsp;&nbsp;Follicular phase || 1.3 || 1.36 || 66.0 || 2.26 || 30.4
|-
| &nbsp;&nbsp;Luteal phase || 1.3 || 1.37 || 65.7 || 2.20 || 30.7
|-
| &nbsp;&nbsp;Pregnancy || 4.7 || 0.23 || 95.4 || 0.82 || 3.6
|-
| rowspan="5" | [[Dihydrotestosterone]] || Adult men || 1.70 || 0.88 || 49.7 || 0.22 || 39.2
|-
| colspan="6" | Adult women
|-
| &nbsp;&nbsp;Follicular phase || 0.65 || 0.47 || 78.4 || 0.12 || 21.0
|-
| &nbsp;&nbsp;Luteal phase || 0.65 || 0.48 || 78.1 || 0.12 || 21.3
|-
| &nbsp;&nbsp;Pregnancy || 0.93 || 0.07 || 97.8 || 0.04 || 21.2
|- class="sortbottom"
| colspan="7" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Sources:''' <ref name="NieschlagBehre2012">{{cite book| first1 = Eberhard | last1 = Nieschlag | first2 = Hermann M. | last2 = Behre | first3 = Susan | last3 = Nieschlag | name-list-format = vanc |title=Testosterone: Action, Deficiency, Substitution|url=https://books.google.com/books?id=MkrAPaQ4wJkC&pg=PA61|date=26 July 2012 |publisher=Cambridge University Press |isbn=978-1-107-01290-5 |pages=61–}}</ref><ref name="pmid7195404">{{cite journal | vauthors = Dunn JF, Nisula BC, Rodbard D | title = Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma | journal = J. Clin. Endocrinol. Metab. | volume = 53 | issue = 1 | pages = 58–68 | date = July 1981 | pmid = 7195404 | doi = 10.1210/jcem-53-1-58 | url = }}</ref>
|}
 
===Metabolism===
{{Testosterone metabolism mini|align=right|caption=The [[metabolic pathway]]s involved in the [[metabolism]] of testosterone in humans. In addition to the [[biotransformation|transformation]]s shown in the diagram, [[conjugation (biochemistry)|conjugation]] via [[sulfation]] and [[glucuronidation]] occurs with testosterone and [[metabolite]]s that have one or more available [[hydroxyl group|hydroxyl]] (–OH) [[functional group|group]]s.}}
 
Both testosterone and 5α-DHT are [[metabolism|metabolized]] mainly in the [[liver]].<ref name="MelmedPolonsky2015">{{cite book | first1 = Shlomo | last1 = Melmed | first2 = Kenneth S. | last2 = Polonsky| first3 = P. Reed | last3 = Larsen | first4 = Henry M. | last4 = Kronenberg | name-list-format = vanc | title = Williams Textbook of Endocrinology | url = https://books.google.com/books?id=YZ8_CwAAQBAJ&pg=PA711 | date = 30 November 2015 | publisher = Elsevier Health Sciences|isbn=978-0-323-29738-7 | pages = 711– }}</ref><ref name="Becker2001">{{cite book | first1 = Kenneth L. | last1 = Becker | name-list-format = vanc | title = Principles and Practice of Endocrinology and Metabolism | url = https://books.google.com/books?id=FVfzRvaucq8C&pg=PA1116 | year = 2001 | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-1750-2 | pages = 1116, 1119, 1183 }}</ref> Approximately 50% of testosterone is metabolized via [[conjugation (biochemistry)|conjugation]] into [[testosterone glucuronide]] and to a lesser extent [[testosterone sulfate]] by [[glucuronosyltransferase]]s and [[sulfotransferase]]s, respectively.<ref name="MelmedPolonsky2015" /> An additional 40% of testosterone is metabolized in equal proportions into the [[17-ketosteroid]]s [[androsterone]] and [[etiocholanolone]] via the combined actions of [[5α-reductase|5α-]] and [[5β-reductase]]s, [[3α-hydroxysteroid dehydrogenase]], and 17β-HSD, in that order.<ref name="MelmedPolonsky2015" /><ref name="Becker2001" /><ref name="WeckerWatts2009">{{cite book | first1 = Lynn | last1 = Wecker | first2 = Stephanie | last2 = Watts | first3 = Carl | last3 = Faingold | first4 = George | last4 = Dunaway | first5 = Lynn | last5 = Crespo | name-list-format = vanc | title = Brody's Human Pharmacology | url = https://books.google.com/books?id=kfsrz_-OrMQC&pg=PA468 | date = 1 April 2009 | publisher = Elsevier Health Sciences | isbn = 978-0-323-07575-6 | pages = 468–469 }}</ref> Androsterone and etiocholanolone are then [[glucuronidation|glucuronidated]] and to a lesser extent [[sulfation|sulfated]] similarly to testosterone.<ref name="MelmedPolonsky2015" /><ref name="Becker2001" /> The conjugates of testosterone and its hepatic metabolites are released from the liver into [[circulatory system|circulation]] and [[excretion|excreted]] in the [[urine]] and [[bile]].<ref name="MelmedPolonsky2015" /><ref name="Becker2001" /><ref name="WeckerWatts2009" /> Only a small fraction (2%) of testosterone is excreted unchanged in the urine.<ref name="Becker2001" />
 
In the hepatic 17-ketosteroid pathway of testosterone metabolism, testosterone is converted in the liver by 5α-reductase and 5β-reductase into 5α-DHT and the inactive [[5β-Dihydrotestosterone|5β-DHT]], respectively.<ref name="MelmedPolonsky2015" /><ref name="Becker2001" /> Then, 5α-DHT and 5β-DHT are converted by 3α-HSD into [[3α-androstanediol]] and [[3α-etiocholanediol]], respectively.<ref name="MelmedPolonsky2015" /><ref name="Becker2001" /> Subsequently, 3α-androstanediol and 3α-etiocholanediol are converted by 17β-HSD into androsterone and etiocholanolone, which is followed by their conjugation and excretion.<ref name="MelmedPolonsky2015" /><ref name="Becker2001" /> [[3β-Androstanediol]] and [[3β-etiocholanediol]] can also be formed in this pathway when 5α-DHT and 5β-DHT are acted upon by 3β-HSD instead of 3α-HSD, respectively, and they can then be transformed into [[epiandrosterone]] and [[epietiocholanolone]], respectively.<ref name="pmid20186052">{{cite journal | vauthors = Penning TM | title = New frontiers in androgen biosynthesis and metabolism | journal = Curr Opin Endocrinol Diabetes Obes | volume = 17 | issue = 3 | pages = 233–9 | year = 2010 | pmid = 20186052 | pmc = 3206266 | doi = 10.1097/MED.0b013e3283381a31 | url = }}</ref><ref name="HorskyPresl2012">{{cite book | vauthors = Horsky J, Presl J | name-list-format = vanc | title = Ovarian Function and its Disorders: Diagnosis and Therapy | url = https://books.google.com/books?id=7IrpCAAAQBAJ&pg=PA107 | date = 6 December 2012 | publisher = Springer Science & Business Media | isbn = 978-94-009-8195-9 | pages = 107– }}</ref> A small portion of approximately 3% of testosterone is [[reversible reaction|reversibly]] converted in the liver into [[androstenedione]] by 17β-HSD.<ref name="WeckerWatts2009" />
 
In addition to conjugation and the 17-ketosteroid pathway, testosterone can also be [[hydroxylation|hydroxylated]] and [[oxidation|oxidized]] in the liver by [[cytochrome P450]] [[enzyme]]s, including [[CYP3A4]], [[CYP3A5]], [[CYP2C9]], [[CYP2C19]], and [[CYP2D6]].<ref name="Zhou2016">{{cite book | first = Shufeng | last = Zhou | name-list-format = vanc | title=Cytochrome P450 2D6: Structure, Function, Regulation and Polymorphism | url = https://books.google.com/books?id=UJqmCwAAQBAJ&pg=PA242|date=6 April 2016 | publisher = CRC Press | isbn = 978-1-4665-9788-4 | pages = 242– }}</ref> 6β-Hydroxylation and to a lesser extent 16β-hydroxylation are the major transformations.<ref name="Zhou2016" /> The 6β-hydroxylation of testosterone is catalyzed mainly by CYP3A4 and to a lesser extent CYP3A5 and is responsible for 75 to 80% of cytochrome P450-mediated testosterone metabolism.<ref name="Zhou2016" /> In addition to 6β- and 16β-hydroxytestosterone, 1β-, 2α/β-, 11β-, and 15β-hydroxytestosterone are also formed as minor metabolites.<ref name="Zhou2016" /><ref name="isbn0-3870-8012-0">{{cite book | vauthors = Trager L | title = Steroidhormone: Biosynthese, Stoffwechsel, Wirkung | edition = | language = German | publisher = Springer-Verlag | location = | year = 1977 | origyear = | page = 349 | quote = | isbn = 978-0-387-08012-3 | oclc = | doi = | accessdate = }}</ref> Certain cytochrome P450 enzymes such as CYP2C9 and CYP2C19 can also oxidize testosterone at the C17 position to form androstenedione.<ref name="Zhou2016" />
 
Two of the immediate metabolites of testosterone, 5α-DHT and [[estradiol]], are biologically important and can be formed both in the liver and in extrahepatic tissues.<ref name="Becker2001" /> Approximately 5 to 7% of testosterone is converted by 5α-reductase into 5α-DHT, with circulating levels of 5α-DHT about 10% of those of testosterone, and approximately 0.3% of testosterone is converted into estradiol by [[aromatase]].<ref name="Mooradian_ 1987"/><ref name="Becker2001" /><ref name="pmid8092979">{{cite journal | vauthors = Randall VA | title = Role of 5 alpha-reductase in health and disease | journal = Baillière's Clinical Endocrinology and Metabolism | volume = 8 | issue = 2 | pages = 405–31 | date = Apr 1994 | pmid = 8092979 | doi = 10.1016/S0950-351X(05)80259-9 }}</ref><ref name="pmid12428207">{{cite journal | vauthors = Meinhardt U, Mullis PE | title = The essential role of the aromatase/p450arom | journal = Seminars in Reproductive Medicine | volume = 20 | issue = 3 | pages = 277–84 | date = Aug 2002 | pmid = 12428207 | doi = 10.1055/s-2002-35374 }}</ref> 5α-Reductase is highly expressed in the [[male reproductive system|male reproductive organ]]s (including the [[prostate gland]], [[seminal vesicle]]s, and [[epididymides]]),<ref name="Noakes2009">{{cite book | first = David E. | last = Noakes | name-list-format = vanc | title=Arthur's Veterinary Reproduction and Obstetrics | url = https://books.google.com/books?id=W5TdAwAAQBAJ&pg=PA695 | date = 23 April 2009 | publisher = Elsevier Health Sciences UK | isbn = 978-0-7020-3990-4 | pages = 695– }}</ref> [[skin]], [[hair follicle]]s, and [[brain]]<ref name="NieschlagBehre2004">{{cite book | vauthors = Nieschlag E, Behre HM | title = Testosterone: Action, Deficiency, Substitution | url = https://books.google.com/books?id=ZiZ7MWDqo5oC&pg=PA626 | date = 1 April 2004 | publisher = Cambridge University Press | isbn = 978-1-139-45221-2 | pages = 626– }}</ref> and aromatase is highly expressed in adipose tissue, [[bone]], and the brain.<ref name="Parl2000">{{cite book | first = Fritz F. | last = Parl | name-list-format = vanc | title = Estrogens, Estrogen Receptor and Breast Cancer | url = https://books.google.com/books?id=v7ai5Mz9TZQC&pg=PA25 | year = 2000 | publisher = IOS Press | isbn = 978-0-9673355-4-4 | pages = 25– }}</ref><ref name="NormanHenry2014">{{cite book | first1 = Anthony W. | last1 = Norman | first2 = Helen L. | last2 = Henry | name-list-format = vanc | title = Hormones|url=https://books.google.com/books?id=_renonjXq68C&pg=PA261 | date=30 July 2014 | publisher = Academic Press | isbn = 978-0-08-091906-5 | pages = 261– }}</ref> As much as 90% of testosterone is converted into 5α-DHT in so-called androgenic tissues with high 5α-reductase expression,<ref name="WeckerWatts2009" /> and due to the several-fold greater potency of 5α-DHT as an AR agonist relative to testosterone,<ref name="MozayaniRaymon2011">{{cite book | first1 = Ashram | last1 = Mozayani | first2 = Lionel | last2 = Raymon | name-list-format = vanc | title = Handbook of Drug Interactions: A Clinical and Forensic Guide | url = https://books.google.com/books?id=NhBJ6kg_uP0C&pg=PA656 | date = 18 September 2011 | publisher = Springer Science & Business Media | isbn = 978-1-61779-222-9 | pages = 656– }}</ref> it has been estimated that the effects of testosterone are potentiated 2- to 3-fold in such tissues.<ref name="pmid7626464">{{cite journal | vauthors = Sundaram K, Kumar N, Monder C, Bardin CW | title = Different patterns of metabolism determine the relative anabolic activity of 19-norandrogens | journal = J. Steroid Biochem. Mol. Biol. | volume = 53 | issue = 1–6 | pages = 253–7 | year = 1995 | pmid = 7626464 | doi = 10.1016/0960-0760(95)00056-6| url = }}</ref>
 
===Levels===
Total levels of testosterone in the body are 264 to 916&nbsp;ng/dL in men age 19 to 39&nbsp;years,<ref name="pmid28324103">{{cite journal | vauthors = Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, Lapauw B, Fiers T, Matsumoto AM, Bhasin S | title = Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 102 | issue = 4 | pages = 1161–1173 | date = April 2017 | pmid = 28324103 | pmc = 5460736 | doi = 10.1210/jc.2016-2935 }}</ref> while mean testosterone levels in adult men have been reported as 630&nbsp;ng/dL.<ref name="Sperling2014" /> Levels of testosterone in men decline with age.<ref name="pmid28324103" /> In women, mean levels of total testosterone have been reported to be 32.6&nbsp;ng/dL.<ref name="Camacho2012">{{cite book|author=Pauline M. Camacho|title=Evidence-Based Endocrinology|url=https://books.google.com/books?id=s06wXkPAnfcC&pg=PA217|date=26 September 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-7146-4|pages=217–}}</ref><ref name="pmid15251757">{{cite journal | vauthors = Steinberger E, Ayala C, Hsi B, Smith KD, Rodriguez-Rigau LJ, Weidman ER, Reimondo GG | title = Utilization of commercial laboratory results in management of hyperandrogenism in women | journal = Endocr Pract | volume = 4 | issue = 1 | pages = 1–10 | date = 1998 | pmid = 15251757 | doi = 10.4158/EP.4.1.1 | url = }}</ref> In women with [[hyperandrogenism]], mean levels of total testosterone have been reported to be 62.1&nbsp;ng/dL.<ref name="Camacho2012" /><ref name="pmid15251757" />
 
{{Testosterone levels in males and females}}
 
{| class="wikitable mw-collapsible mw-collapsed" style="text-align:left; margin-left:auto; margin-right:auto; border:none;"
|+ class="nowrap" | Total testosterone levels in males throughout life
|-
! Life stage !! Tanner stage !! Age range !! Mean age !! Levels range !! Mean levels
|-
| Child || Stage I || <10 years || – || <30&nbsp;ng/dL || 5.8&nbsp;ng/dL
|-
| rowspan="4" | Puberty || Stage II || 10–14 years || 12 years || <167&nbsp;ng/dL || 40&nbsp;ng/dL
|-
| Stage III || 12–16 years || 13–14 years || 21–719&nbsp;ng/dL || 190&nbsp;ng/dL
|-
| Stage IV || 13–17 years || 14–15 years || 25–912&nbsp;ng/dL || 370&nbsp;ng/dL
|-
| Stage V || 13–17 years || 15 years || 110–975&nbsp;ng/dL || 550&nbsp;ng/dL
|-
| Adult || – || ≥18 years || – || 250–1,100&nbsp;ng/dL || 630&nbsp;ng/dL
|- class="sortbottom"
| colspan="6" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Sources:''' <ref name="BajajBerman2011">{{cite book | first1 = Lalit | last1 = Bajaj | first2 = Stephen | last2 = Berman | name-list-format = vanc |title=Berman's Pediatric Decision Making|url=https://books.google.com/books?id=NPhnHrDQ1_kC&pg=PA160|date=1 January 2011|publisher=Elsevier Health Sciences|isbn=978-0-323-05405-8|pages=160–}}</ref><ref name="BajajBerman2011" /><ref name="Styne2016">{{cite book|author=Dennis M. Styne|title=Pediatric Endocrinology: A Clinical Handbook|url=https://books.google.com/books?id=akMWDAAAQBAJ&pg=PA191|date=25 April 2016|publisher=Springer|isbn=978-3-319-18371-8|pages=191–}}</ref><ref name="Sperling2014">{{cite book| first = Mark A. | last = Sperling | name-list-format = vanc |title=Pediatric Endocrinology E-Book|url=https://books.google.com/books?id=GgXnAgAAQBAJ&pg=PA488|date=10 April 2014|publisher=Elsevier Health Sciences|isbn=978-1-4557-5973-6|pages=488–}}</ref><ref name="PaganaPagana2014">{{cite book | first1 = Kathleen Deska | last1 = Pagana | first2 = Timothy J. | last2 = Pagana | first3 = Theresa N | last3 = Pagana | name-list-format = vanc |title=Mosby's Diagnostic and Laboratory Test Reference – E-Book |url=https://books.google.com/books?id=J7eXBAAAQBAJ&pg=PA879 |date=19 September 2014 |publisher=Elsevier Health Sciences |isbn=978-0-323-22592-2 |pages=879–}}</ref><ref name="HospitalEngorn2014">{{cite book | first1 = Branden | last1 = Engorn | first2 = Jamie | last2 = Flerlage | name-list-format = vanc |title=The Harriet Lane Handbook E-Book |url=https://books.google.com/books?id=6cSLAwAAQBAJ&pg=PA240 |date=1 May 2014 |publisher=Elsevier Health Sciences |isbn=978-0-323-11246-8 |pages=240–}}</ref>
|}
 
[[File:Blood values sorted by mass and molar concentration.png|thumb|left|700px|[[Reference ranges for blood tests]], showing adult male testosterone levels in light blue at center-left.]]{{Clear}}
 
==Measurement==
Testosterone's bioavailable concentration is commonly determined using the Vermeulen calculation or more precisely using the modified Vermeulen method,<ref name="Jong">{{cite journal | vauthors = de Ronde W, van der Schouw YT, Pols HA, Gooren LJ, Muller M, Grobbee DE, de Jong FH | title = Calculation of bioavailable and free testosterone in men: a comparison of 5 published algorithms | journal = Clinical Chemistry | volume = 52 | issue = 9 | pages = 1777–84 | date = September 2006 | pmid = 16793931 | doi = 10.1373/clinchem.2005.063354 }}</ref><ref>{{cite journal | vauthors = Hasler J, Herklotz R, Luppa PB, Diver MJ, Thevis M, Metzger J, Savoca R, Jermini F, Huber AR |title=Impact of recent biochemical findings on the determination of free and bioavailable testosterone: evaluation and proposal for clinical use |journal=LaboratoriumsMedizin |date=1 January 2006 |volume=30 |issue=6 |pages=492–505 |doi=10.1515/JLM.2006.050 }}</ref> which considers the dimeric form of sex-hormone-binding-globulin.<ref name="PDB">https://www.rcsb.org/3d-view/1D2S/1</ref>
 
Both methods use chemical equilibrium to derive the concentration of bioavailable testosterone: in circulation testosterone has two major binding partners, albumin (weakly bound) and sex-hormone-binding-globulin (strongly bound). These methods are described in detail in the accompanying figure.
 
<gallery>
File:Dimeric SHBG.png|Dimeric sex-hormone-binding-globulin with its testosterone ligands
File:Method for determining testosterone.png|Two methods for determining concentration of bioavailable testosterone.
</gallery>
 
==History==
A [[testicular]] action was linked to circulating blood fractions&nbsp;– now understood to be a family of androgenic hormones&nbsp;– in the early work on castration and testicular transplantation in fowl by [[Arnold Adolph Berthold]] (1803–1861).<ref name="Berthold_1849">{{cite journal | vauthors = Berthold AA | title = Transplantation der Hoden |trans-title=Transplantation of testis | language = German | journal = Arch. Anat. Physiol. Wiss. |volume = 16 |issue = |pages = 42–6 | year = 1849 | pmid = | doi= | url =}}</ref> Research on the action of testosterone received a brief boost in 1889, when the Harvard professor [[Charles-Édouard Brown-Séquard]] (1817–1894), then in Paris, self-injected subcutaneously a "rejuvenating elixir" consisting of an extract of dog and guinea pig testicle. He reported in ''[[The Lancet]]'' that his vigor and feeling of well-being were markedly restored but the effects were transient,<ref name="Brown-Sequard_1889">{{cite journal | vauthors = Brown-Sequard CE | title = The effects produced on man by subcutaneous injections of liquid obtained from the testicles of animals | journal = Lancet |volume = 2 | issue = 3438|pages = 105–07| year = 1889 | doi = 10.1016/S0140-6736(00)64118-1 | url = https://zenodo.org/record/1428532 }}</ref> and Brown-Séquard's hopes for the compound were dashed. Suffering the ridicule of his colleagues, he abandoned his work on the mechanisms and effects of androgens in human beings.
 
In 1927, the University of Chicago's Professor of Physiologic Chemistry, Fred C. Koch, established easy access to a large source of bovine testicles — the Chicago stockyards — and recruited students willing to endure the tedious work of extracting their isolates. In that year, Koch and his student, Lemuel McGee, derived 20&nbsp;mg of a substance from a supply of 40 pounds of bovine testicles that, when administered to castrated roosters, pigs and rats, remasculinized them.<ref name="Gallagher_Koch_1929">{{cite journal | vauthors = Gallagher TF, Koch FC | title = The testicular hormone |journal = J. Biol. Chem. | volume = 84 | issue = 2 | pages = 495–500 |date=November 1929 | pmid = | doi = }}</ref> The group of Ernst Laqueur at the University of Amsterdam purified testosterone from bovine testicles in a similar manner in 1934, but isolation of the hormone from animal tissues in amounts permitting serious study in humans was not feasible until three European pharmaceutical giants—[[Schering AG|Schering]] (Berlin, Germany), [[Organon International|Organon]] (Oss, Netherlands) and [[Novartis|Ciba]] (Basel, Switzerland)—began full-scale steroid research and development programs in the 1930s.
 
[[File:Lavoslav Ružićka 1939.jpg|thumb|200px|Nobel Prize winner, Leopold Ruzicka of Ciba, a pharmaceutical industry giant that synthesized testosterone.]]
 
The Organon group in the Netherlands were the first to isolate the hormone, identified in a May 1935 paper "On Crystalline Male Hormone from Testicles (Testosterone)".<ref name="David_1935">{{cite journal | vauthors = David KG, Dingemanse E, Freud JL | title = Über krystallinisches mannliches Hormon aus Hoden (Testosteron) wirksamer als aus harn oder aus Cholesterin bereitetes Androsteron |trans-title=On crystalline male hormone from testicles (testosterone) effective as from urine or from cholesterol | language = German | journal = Hoppe-Seyler's Z Physiol Chem | volume = 233 | issue = 5–6| pages = 281–83 |date=May 1935 | pmid = | doi = 10.1515/bchm2.1935.233.5-6.281 }}</ref> They named the hormone ''testosterone'', from the [[stem (linguistics)|stems]] of ''testicle'' and ''[[sterol]]'', and the [[suffix]] of ''[[ketone]]''. The structure was worked out by Schering's [[Adolf Butenandt]], at the [[Faculty of Chemistry, Gdańsk University of Technology|''Chemisches Institut'']] of [[Gdańsk University of Technology|Technical University]] in [[Gdańsk]].<ref name="Butenandt_1935a">{{cite journal | vauthors = Butenandt A, Hanisch G | title = Umwandlung des Dehydroandrosterons in Androstendiol und Testosterone; ein Weg zur Darstellung des Testosterons aus Cholestrin |trans-title=About Testosterone. Conversion of Dehydro-androsterons into androstendiol and testosterone; a way for the structure assignment of testosterone from cholesterol | language = German | journal = Hoppe-Seyler's Z Physiol Chem | volume = 237 | issue = 2| pages = 89–97 | year = 1935 | pmid = | doi = 10.1515/bchm2.1935.237.1-3.89 }}</ref><ref name="pmid11176375">{{cite journal | vauthors = Freeman ER, Bloom DA, McGuire EJ | title = A brief history of testosterone | journal = The Journal of Urology | volume = 165 | issue = 2 | pages = 371–73 | date = Feb 2001 | pmid = 11176375 | doi = 10.1097/00005392-200102000-00004 }}</ref>
 
The [[chemical synthesis]] of testosterone from cholesterol was achieved in August that year by Butenandt and Hanisch.<ref name="Butenandt_1935b">{{cite journal | vauthors = Butenandt A, Hanisch G | title = Uber die Umwandlung des Dehydroandrosterons in Androstenol-(17)-one-(3) (Testosterone); um Weg zur Darstellung des Testosterons auf Cholesterin (Vorlauf Mitteilung). [The conversion of dehydroandrosterone into androstenol-(17)-one-3 (testosterone); a method for the production of testosterone from cholesterol (preliminary communication)] | journal = Chemische Berichte | year = 1935 | volume = 68 | issue = 9 | pages = 1859–62 | language = German | doi = 10.1002/cber.19350680937 }}</ref> Only a week later, the Ciba group in Zurich, [[Leopold Ruzicka]] (1887–1976) and A. Wettstein, published their synthesis of testosterone.<ref name="Ruzicka_1935">{{cite journal | vauthors = Ruzicka L, Wettstein A | title = Uber die kristallinische Herstellung des Testikelhormons, Testosteron (Androsten-3-ol-17-ol) [The crystalline production of the testicle hormone, testosterone (Androsten-3-ol-17-ol)] | journal = Helvetica Chimica Acta | year = 1935 | volume = 18 | pages = 1264–75 | language = German | doi=10.1002/hlca.193501801176}}</ref> These independent partial syntheses of testosterone from a cholesterol base earned both Butenandt and Ruzicka the joint 1939 [[Nobel Prize in Chemistry]].<ref name="pmid11176375"/><ref name="pmid7817189">{{cite journal | vauthors = Hoberman JM, Yesalis CE | title = The history of synthetic testosterone | journal = Scientific American | volume = 272 | issue = 2 | pages = 76–81 | date = Feb 1995 | pmid = 7817189 | doi = 10.1038/scientificamerican0295-76 | bibcode = 1995SciAm.272b..76H }}</ref> Testosterone was identified as 17β-hydroxyandrost-4-en-3-one (C<sub>19</sub>H<sub>28</sub>O<sub>2</sub>), a solid polycyclic alcohol with a hydroxyl group at the 17th carbon atom. This also made it obvious that additional modifications on the synthesized testosterone could be made, i.e., esterification and alkylation.
 
The partial synthesis in the 1930s of abundant, potent [[testosterone ester]]s permitted the characterization of the hormone's effects, so that Kochakian and Murlin (1936) were able to show that testosterone raised nitrogen retention (a mechanism central to anabolism) in the dog, after which Allan Kenyon's group<ref name=" Kenyon _1940">{{cite journal | vauthors = Kenyon AT, Knowlton K, Sandiford I, Koch FC, Lotwin, G | title = A comparative study of the metabolic effects of testosterone propionate in normal men and women and in eunuchoidism | journal = Endocrinology | volume = 26| issue = 1 | pages = 26–45 |date=February 1940| doi = 10.1210/Endo-26-1-26 | url = }}</ref> was able to demonstrate both anabolic and androgenic effects of testosterone propionate in eunuchoidal men, boys, and women. The period of the early 1930s to the 1950s has been called "The Golden Age of Steroid Chemistry",<ref name="pmid10443899">{{cite journal | vauthors = Schwarz S, Onken D, Schubert A | title = The steroid story of Jenapharm: from the late 1940s to the early 1970s | journal = Steroids | volume = 64 | issue = 7 | pages = 439–45 | date = Jul 1999 | pmid = 10443899 | doi = 10.1016/S0039-128X(99)00003-3 }}</ref> and work during this period progressed quickly. Research in this golden age proved that this newly synthesized compound—testosterone—or rather family of compounds (for many derivatives were developed from 1940 to 1960), was a potent multiplier of muscle, strength, and well-being.<ref name = "de Kruif_1945" >{{cite book | vauthors = de Kruif P | title = The Male Hormone | publisher = Harcourt, Brace | location = New York |year = 1945 }}</ref>
 
==Other animals==
Testosterone is observed in most vertebrates. Testosterone and the classical nuclear [[androgen receptor]] first appeared in [[gnathostome]]s (jawed vertebrates).<ref name="pmid19456336">{{cite journal | vauthors = Guerriero G | title = Vertebrate sex steroid receptors: evolution, ligands, and neurodistribution | journal = Annals of the New York Academy of Sciences | volume = 1163 | issue = 1| pages = 154–68 | year = 2009 | pmid = 19456336 | doi = 10.1111/j.1749-6632.2009.04460.x | bibcode = 2009NYASA1163..154G }}</ref> [[Agnathan]]s (jawless vertebrates) such as [[lamprey]]s do not produce testosterone but instead use [[androstenedione]] as a male sex hormone.<ref name="pmid17931674">{{cite journal | vauthors = Bryan MB, Scott AP, Li W | title = Sex steroids and their receptors in lampreys | journal = Steroids | volume = 73 | issue = 1 | pages = 1–12 | year = 2008 | pmid = 17931674 | doi = 10.1016/j.steroids.2007.08.011 }}</ref> [[Fish]] make a slightly different form called [[11-ketotestosterone]].<ref name="isbn0-87893-617-3">{{cite book | vauthors = Nelson RF | title = An introduction to behavioral endocrinology | edition = | publisher = Sinauer Associates | location = Sunderland, Mass | year = 2005 | origyear = | page = 143 | quote = | isbn = 978-0-87893-617-5 }}</ref> Its counterpart in insects is [[ecdysone]].<ref name="De_Loof_2006">{{cite journal | vauthors = De Loof A | title = Ecdysteroids: the overlooked sex steroids of insects? Males: the black box | journal = Insect Science |date=October 2006 | volume = 13 | issue = 5 | pages = 325–338 | doi = 10.1111/j.1744-7917.2006.00101.x }}</ref> The presence of these ubiquitous steroids in a wide range of animals suggest that [[sex hormone]]s have an ancient evolutionary history.<ref name="Mechoulam_1984">{{cite journal | vauthors = Mechoulam R, Brueggemeier RW, Denlinger DL | title = Estrogens in insects | journal = Journal Cellular and Molecular Life Sciences |date=September 1984 | volume = 40 | issue = 9 | pages = 942–44 | doi = 10.1007/BF01946450 }}</ref>
 
==See also==
* [[List of androgens/anabolic steroids]]
 
==References==
{{Reflist}}
 
==Further reading==
{{refbegin}}
* {{cite book | veditors = Pfaff DW, Etgen AM | vauthors = Fargo KN, Pak TR, Foecking EM, Jones KJ | title = Molecular Mechanisms of Hormone Actions on Behavior | chapter = Molecular Biology of Androgen Action: Perspectives on Neuroprotective and Neurotherapeutic Effects. | publisher = Elsevier Inc. | date = 2010 | pages = 1219–1246 | doi = 10.1016/B978-008088783-8.00036-X | isbn = 978-0-12-374939-0 | chapter-url = https://books.google.com/books?id=Y8jxd5vu6N8C&pg=PA127#v=onepage&q&f=false }}
* {{cite journal | last = Dowd | first = Nancy E. | name-list-format = vanc |title= Sperm, testosterone, masculinities and fatherhood | journal = Nevada Law Journal | volume = 13 | issue = 2 | page = 8 | url = http://scholars.law.unlv.edu/nlj/vol13/iss2/8 | date = 2013 }}
{{refend}}
<nowiki>
{{Portal bar|Chemistry|Biology|Pharmacy and pharmacology}}
 
{{Testosterone}}
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{{Navboxes
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[[Category:Cyclopentanols]]
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[[Category:Estrogens]]<!--Via metabolism into estradiol and androstanediols-->
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[[Category:Hormones of the testis]]
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</nowiki>
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