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| − | {{Drugbox| |
+ | {{Drugbox| Watchedfields = changed |
| + | | verifiedrevid = 265997766 |
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| − | |IUPAC_name = (8R,9S,10R,13S,14S,17S)- 17-hydroxy-10,13-dimethyl- 1,2,6,7,8,9,11,12,14,15,1 |
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| − | 6,17- dodecahydrocyclopenta[a] |
+ | | IUPAC_name = (8''R'',9''S'',10''R'',13''S'',14''S'',17''S'')- 17-hydroxy-10,13-dimethyl- 1,2,6,7,8,9,11,12,14,15,16,17- dodecahydrocyclopenta[''a'']phenanthren-3-one |
| − | | image= |
+ | | image = Testosterone.svg |
| − | | width= |
+ | | width = 200px |
| image2=Testosterone-from-xtal-3D-balls.png |
| image2=Testosterone-from-xtal-3D-balls.png |
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| − | | smiles=C[C@]43CCC(=O)\C=C4\CC |
+ | | smiles=C[C@]43CCC(=O)\C=C4\CC[C@@H]1[C@@H]3CC[C@]2(C)[C@@H](O)CC[C@@H]12 |
| CAS_number=58-22-0 |
| CAS_number=58-22-0 |
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| CASNo_Ref = {{cascite}} |
| CASNo_Ref = {{cascite}} |
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| ATC_supplemental= |
| ATC_supplemental= |
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| PubChem=6013 |
| PubChem=6013 |
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| − | | DrugBank= |
+ | | DrugBank=DB00624 |
| C=19 | H=28 | O=2 |
| C=19 | H=28 | O=2 |
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| molecular_weight = 288.42 |
| molecular_weight = 288.42 |
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| sec_combustion=−11080 kJ/mol |
| sec_combustion=−11080 kJ/mol |
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}} |
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| − | '''Testosterone''' is a [[steroid hormone]] from the [[androgen]] group. In mammals, testosterone is primarily secreted in the [[testis|testes]] of males and the [[ovaries]] of females, although small amounts are also secreted by the [[adrenal gland]]s. It is the principal [[male]] sex [[hormone]] and an [[anabolic steroid]]. |
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| + | '''Testosterone''' is a [[steroid hormone]] from the [[androgen]] group and is found in mammals, reptiles,<ref name="pmid16326949">{{cite journal | author = Cox RM, John-Alder HB | title = Testosterone has opposite effects on male growth in lizards (Sceloporus spp.) with opposite patterns of sexual size dimorphism | journal = J. Exp. Biol. | volume = 208 | issue = Pt 24 | pages = 4679–87 | year = 2005 | month = December | pmid = 16326949 | doi = 10.1242/jeb.01948 | url = | issn = }}</ref> birds,<ref name="pmid16671011">{{cite journal | author = Reed WL, Clark ME, Parker PG, Raouf SA, Arguedas N, Monk DS, Snajdr E, Nolan V, Ketterson ED | title = Physiological effects on demography: a long-term experimental study of testosterone's effects on fitness | journal = Am. Nat. | volume = 167 | issue = 5 | pages = 667–83 | year = 2006 | month = May | pmid = 16671011 | doi = 10.1086/503054 | laysummary = http://www.sciencedaily.com/releases/2006/05/060526083618.htm | laysource = ScienceDaily }}</ref> and other [[vertebrate]]s. In [[mammal]]s, testosterone is primarily secreted in the [[testis|testes]] of [[male]]s and the [[ovaries]] of [[female]]s, although small amounts are also secreted by the [[adrenal gland]]s. It is the principal [[male]] sex [[hormone]] and an [[anabolic steroid]]. |
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| ⚫ | |||
| + | In men, testosterone plays a key role in the development of male reproductive tissues such as the [[testis]] and [[prostate]] as well as promoting secondary sexual characteristics such as increased [[muscle]], [[bone]] mass and [[hair]] growth.<ref name="Mooradian_ 1987">{{cite journal | author = Mooradian AD, Morley JE, Korenman SG | title = Biological actions of androgens | journal = Endocr. Rev. | volume = 8 | issue = 1 | pages = 1–28 | year = 1987 | month = February | pmid = 3549275 | doi = 10.1210/edrv-8-1-1 | url = | issn = }}</ref> In addition, testosterone is essential for health and well-being<ref name="pmid19707253">{{cite journal | author = Bassil N, Alkaade S, Morley JE | title = The benefits and risks of testosterone replacement therapy: a review | journal = Ther Clin Risk Manag | volume = 5 | issue = 3 | pages = 427–48 | year = 2009 | month = June | pmid = 19707253 | pmc = 2701485 | doi = | url = | issn = }}</ref> as well as the prevention of [[osteoporosis]].<ref name="pmid19011293">{{cite journal | author = Tuck SP, Francis RM | title = Testosterone, bone and osteoporosis | journal = Front Horm Res | volume = 37 | issue = | pages = 123–32 | year = 2009 | pmid = 19011293 | doi = 10.1159/000176049 | url = | issn = }}</ref> |
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| − | ==History== |
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| − | A [[testicular]] action was linked to circulating blood fractions—now understood to be a family of androgenic hormones—in the early work on castration and testicular transplantation in fowl by [[Arnold Adolph Berthold]] (1803–1861). 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 wellbeing were markedly restored but, predictably, the effects were transient (and likely based on placebo), and Brown-Séquard’s hopes for the compound were dashed. Suffering the ridicule of his colleagues, his work on the mechanisms and effects of androgens in human beings was abandoned by Brown-Séquard and succeeding generations of biochemists for nearly 40 years. |
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| ⚫ | On average, an adult [[human]] male body produces about ten times more testosterone than an adult human female body, but females are, from a behavioral perspective (rather than from an anatomical or biological perspective {{Citation needed|date=August 2010}}), more sensitive to the hormone.<ref name="isbn0-07-135739-4">{{cite book | author = Dabbs M, Dabbs JM | authorlink = | editor = | others = | title = Heroes, rogues, and lovers: testosterone and behavior | edition = | language = | publisher = McGraw-Hill | location = New York | year = 2000 | origyear = | pages = | quote = | isbn = 0-07-135739-4 | oclc = | doi = | url = | accessdate = }}</ref> However, the overall ranges for male and female are very wide, such that the ranges actually overlap at the low end and high end respectively {{Citation needed|date=August 2010}}. |
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| − | The trail remained cold until 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 to students willing to endure the ceaseless toil of extracting their isolates. In 1927, Koch and his student, Lemuel McGee, derived 20 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>Gallagher and Koch, 1929.</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 (Berlin, Germany), Organon (Oss, Netherlands) and Ciba (Basel, Switzerland)—began full-scale steroid research and development programs in the 1930’s. |
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| + | Testosterone is conserved through most vertebrates, although [[fish]] make a slightly different form called [[11-ketotestosterone]].<ref name="isbn0-87893-617-3">{{cite book | author = Nelson, Randy F. | authorlink = | editor = | others = | title = An introduction to behavioral endocrinology | edition = | language = | publisher = Sinauer Associates | location = Sunderland, Mass | year = 2005 | origyear = | pages = 143 | quote = | isbn = 0-87893-617-3 | oclc = | doi = | url = | accessdate = }}</ref> Its counterpart in insects is [[ecdysone]].<ref name="De_Loof_2006">{{ cite journal | last = De Loof A | title = Ecdysteroids: the overlooked sex steroids of insects? Males: the black box | journal = Insect Science | year = 2006 | month = October | volume = 13 | issue = 5 | pages = 325–338 | doi = 10.1111/j.1744-7917.2006.00101.x | first1 = Arnold}}</ref> These ubiquitous steroids suggest that [[sex hormone]]s have an ancient evolutionary history.<ref name="Mechoulam_1984">{{cite journal|last=Mechoulam R, Brueggemeier RW, Denlinger DL|title=Estrogens in insects|journal=Journal Cellular and Molecular Life Sciences|year=1984|month=September|volume=40|issue=9|pages=942–944|doi=10.1007/BF01946450|first1=R.|last2=Brueggemeier|first2=R. W.|last3=Denlinger|first3=D. L.}}</ref> |
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| − | 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)" by Karoly Gyula David, E. Dingemanse, J. Freud and Ernst Laqueur. 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 (1903–1995). |
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| + | Of interest to psychologists are: |
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| − | The [[chemical synthesis]] of testosterone was achieved in August that year, when Butenandt and G. Hanisch published a paper describing "A Method for Preparing Testosterone from Cholesterol." Only a week later, the Ciba group in Zurich, Leopold Ruzicka (1887–1976) and A. Wettstein, announced a patent application in a paper "On the Artificial Preparation of the Testicular Hormone Testosterone (Androsten-3-one-17-ol)." These independent partial syntheses of testosterone from a cholesterol base earned both Butenandt and Ruzicka the joint 1939 Nobel Prize in Chemistry.<ref>Hoberman and Yesalis 1995, Freeman ''et al.'' 2001.</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. |
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| + | ==The link between testosterone and thoughts, feelings and behavior== |
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| − | The partial synthesis in the 1930s of abundant, potent testosterone esters 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 Charles Kenyon’s group<ref>Kenyon ''et al.'' 1940.</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 |author=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 |year=1999 |month=July |pmid=10443899 |doi=10.1016/S0039-128X(99)00003-3 |url = http://www.ingentaconnect.com/content/els/0039128x/1999/00000064/00000007/art00003}}</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 wellbeing.<ref>deKruif, 1945.</ref> |
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| + | Testosterone has been associated with a broad array of psychological effects. |
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| ⚫ | |||
| − | ==Production== |
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| + | * Studies show that falling in love decreases men's testosterone levels while increasing women's testosterone levels. It is speculated that these changes in testosterone result in the temporary reduction of differences in behavior between the sexes.<ref>Marazziti D, Canale D. 2004.Hormonal changes when falling in love. Psychoneuroendocrinology 29(7): 931-936.</ref> |
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| + | ==Testosterone and risk taking== |
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| − | ===Natural=== |
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| + | * Recent studies suggest that testosterone level plays a major role in risk-taking during financial decisions.<ref name="pmid19706398">{{cite journal | author = Sapienza P, Zingales L, Maestripieri D | title = Gender differences in financial risk aversion and career choices are affected by testosterone | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 106 | issue = 36 | pages = 15268–73 | year = 2009 | month = September | pmid = 19706398 | doi = 10.1073/pnas.0907352106 | url = | issn = | pmc = 2741240 }}</ref><ref name="Apicella_2008">{{cite journal | author = 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 = 384–390 | year = 2008 | month = November | pmid = | doi = 10.1016/j.evolhumbehav.2008.07.001 | url = | issn = }}</ref> |
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| ⚫ | |||
| + | *Fatherhood also decreases testosterone levels in men, suggesting that the resulting emotional and behavioral changes promote paternal care.<ref>Berg SJ, Wynne-Edwards KE. 2001. Changes in testosterone, cortisol, and estradiol levels in men becoming fathers. Mayo Clinic Proceedings 76(1): 582-592.</ref> |
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| − | Like other [[steroid]] hormones, testosterone is derived from [[cholesterol]]. The largest amounts of testosterone are produced by the [[testis|testes]] in men. It is also synthesized in far smaller quantities in women by the [[ovary|ovaries]], by the [[placenta]], as well as by the [[zona reticularis]] of the [[adrenal cortex]] in both sexes. |
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| − | In the [[testes]], testosterone is produced by the [[Leydig cell]]s. The male [[gonads|generative glands]] also contain [[Sertoli cell]]s which require testosterone for [[spermatogenesis]]. Like most hormones, testosterone is supplied to target [[Tissue (biology)|tissues]] in the [[blood]] where much of it is transported bound to a specific [[plasma protein]], [[sex hormone binding globulin]] (SHBG). |
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| ⚫ | |||
| − | * Loss of [[status]] or [[dominance]] in men.<ref>P.H. Mehta & R.A. Josephs, 2006 http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WGC-4KPP4H5-1&_user=108429&_coverDate=12%2F31%2F2006&_fmt=full&_orig=search&_cdi=6819&view=c&_acct=C000059713&_version=1&_urlVersion=0&_userid=108429&md5=0b42825a9e5f21eaea7dd8ce037ffe85&ref=full</ref> |
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| − | * Mating and Marriage (via female Pheromones)<ref>http://www.newscientist.com/article/mg19626264.600-getting-married-saps-your-testosterone.html</ref> |
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| − | * [[Implicit power motivation]] predicts an increased testosterone release in men.<ref>http://www.ncbi.nlm.nih.gov/pubmed/10603287</ref> |
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| − | * Aging reduces tetosterone release.<ref>http://ajpendo.physiology.org/cgi/content/full/290/1/E34</ref> |
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| ⚫ | |||
| − | * Sleep (REM dream) increases nocturnal testosterone levels.<ref>http://www.sono.org.br/pdf/2008_Andersen_Sleep_Med_Rev.pdf</ref> |
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| − | * Resistance training increase testosterone levels,<ref>http://www.acsm-msse.org/pt/re/msse/fulltext.00005768-200605001-02108.htm</ref> however, in older men, that increase can be avoided by protein ingestion.<ref>{{cite pmid|18455389}}</ref> |
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| − | * Zinc deficiency lowers testosterone levels <ref>{{cite pmid|8875519}}</ref> but over supplementation has no effect on serum testosterone.<ref>{{cite pmid|17882141}}</ref> |
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| + | ===Testosterone and aggression=== |
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| − | ==== Chemical modification ==== |
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| + | {{Main|Testosterone and aggression}} |
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| − | The second importance of the hydroxyl side chain at the C-17 position is that it can not only be esterified, but it can also be alkylated (by Alkylation permits oral steroids, substitution of an ethyl or methyl group for the hydroxyl group). the so-called “17-aa” or alkylated family of androgens such as methyl testosterone, which can be taken up by the digestive tract, and so be easily administered in pill form. |
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| + | There is strong evidence in animals that testosterone is directly associated with aggression, although this correlation is not as strong in humans.<ref>Simpson, K (2001) The role of testosterone in aggression. MJM, 6, 32-40 [http://www.k9events.com/Testosterone.pdf Full text]</ref> |
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| + | In human studies a relationship has been found between measures of testosterone in adolescent males and [[aggression]] <ref>Olweus D, Mattson A, Schalling D, Low H. (1988) Circulating testosterone levels and aggression in adolescent males: a causal analysis. Psychosomatic Medicine 50: 261-272.</ref> with similar results found in women <ref>Ehlers CL, Rickler KC, Hovey JE. (1980) A possible relationship between plasma testosterone and aggressive behavior and socialdominance in man. Psychosomatic Medicine 36: 469-475</ref>. |
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| − | == |
+ | ===Testosterone and sexuality=== |
| + | {{Main|Testosterone and sexual arousal}} |
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| ⚫ | |||
| + | ===Testosterone and social dominance=== |
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| ⚫ | |||
| + | |||
| ⚫ | * ''Androgenic effects'' include [[maturation]] of the [[sex organs]], particularly the [[penis]] and the formation of the [[scrotum]] in |
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| + | ===Testosterone and mental disorders=== |
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| + | |||
| ⚫ | |||
| + | |||
| ⚫ | In general, [[androgens]] promote [[protein synthesis]] and growth of those tissues with [[androgen receptors]]. Testosterone effects can be classified as [[virilization|virilizing]] and [[anabolism|anabolic]], although the distinction is somewhat artificial, as many of the effects can be considered both. Testosterone is anabolic, meaning it builds up bone and muscle mass. |
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| + | |||
| ⚫ | |||
| ⚫ | * ''Androgenic effects'' include [[maturation]] of the [[sex organs]], particularly the [[penis]] and the formation of the [[scrotum]] in the fetus, and after birth (usually at [[puberty]]) a deepening of the voice, growth of the [[beard]] and [[axillary hair]]. Many of these fall into the category of male [[secondary sex characteristics]]. |
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Testosterone effects can also be classified by the age of usual occurrence. For [[postnatal]] effects in both males and females, these are mostly dependent on the levels and duration of circulating free testosterone. |
Testosterone effects can also be classified by the age of usual occurrence. For [[postnatal]] effects in both males and females, these are mostly dependent on the levels and duration of circulating free testosterone. |
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| − | === |
+ | === Prenatal === |
| + | |||
| − | Most of the ''prenatal androgen effects'' occur between 7 and 12 weeks of gestation. |
+ | Most of the ''prenatal androgen effects'' occur between 7 and 12 weeks of the gestation. |
*Genital virilization (midline fusion, [[phallus|phallic]] [[urethra]], scrotal thinning and rugation, [[phallic]] enlargement); although the role of testosterone is far smaller than that of [[Dihydrotestosterone]]. |
*Genital virilization (midline fusion, [[phallus|phallic]] [[urethra]], scrotal thinning and rugation, [[phallic]] enlargement); although the role of testosterone is far smaller than that of [[Dihydrotestosterone]]. |
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*Development of [[prostate]] and [[seminal vesicle]]s |
*Development of [[prostate]] and [[seminal vesicle]]s |
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| + | *[[Gender identity]]<ref name="pmid19403051">{{cite journal | author = Swaab DF, Garcia-Falgueras A | title = Sexual differentiation of the human brain in relation to gender identity and sexual orientation | journal = Funct. Neurol. |volume = 24 | issue = 1 | pages = 17–28 | year = 2009 | pmid = 19403051 | doi = | url = | issn = }}</ref> |
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| − | ===Early infancy |
+ | === Early infancy === |
| ⚫ | ''Early infancy androgen effects'' are the least understood. In the first weeks of life for male infants, testosterone levels rise. The levels remain in a pubertal range for a few months, but usually reach the barely detectable levels of childhood by 4–6 months of age. The function of this rise in humans is unknown. It has been speculated that "brain [[masculinization]]" is occurring since no significant changes have been identified in other parts of the body.{{ |
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| ⚫ | ''Early infancy androgen effects'' are the least understood. In the first weeks of life for male infants, testosterone levels rise. The levels remain in a pubertal range for a few months, but usually reach the barely detectable levels of childhood by 4–6 months of age.<ref name="pmid4715291">{{cite journal | author = Forest MG, Cathiard AM, Bertrand JA | title = Evidence of testicular activity in early infancy | journal = J. Clin. Endocrinol. Metab. | volume = 37 | issue = 1 | pages = 148–51 | year = 1973 | month = July | pmid = 4715291 | doi = 10.1210/jcem-37-1-148| url = | issn = }}</ref><ref name="pmid1379488">{{cite journal | author = Corbier P, Edwards DA, Roffi J | title = The neonatal testosterone surge: a comparative study | journal = Arch Int Physiol Biochim Biophys | volume = 100 | issue = 2 | pages = 127–31 | year = 1992 | pmid = 1379488 | doi = 10.3109/13813459209035274| url = | issn = }}</ref> The function of this rise in humans is unknown. It has been speculated that "brain [[virilization|masculinization]]" is occurring since no significant changes have been identified in other parts of the body.<ref name="pmid18445234">{{cite journal | author = 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 = Eur. J. Neurosci. | volume = 27 | issue = 9 | pages = 2473–80 | year = 2008 | month = May | pmid = 18445234 | doi = 10.1111/j.1460-9568.2008.06216.x | url = | issn = }}</ref>{{Citation needed|date=March 2008}}<!-- have changes in the brain been detected, or is the supposition purely speculative? --> Surprisingly, the male brain is masculinized by testosterone being aromatized into [[estrogen]], which crosses the [[blood-brain barrier]] and enters the male brain, whereas female fetuses have [[alpha-fetoprotein]] which binds up the estrogen so that female brains are not affected.<ref>http://homepage.psy.utexas.edu/homepage/class/psy308/Humm/ReviewofSexualDifferentiation</ref> |
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| − | ===Pre- Peripubertal effects=== |
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| + | |||
| ⚫ | |||
| + | === Pre-peripubertal === |
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| ⚫ | |||
| + | |||
| ⚫ | |||
| + | androgen levels at the end of childhood, occurring in both boys and girls. |
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| ⚫ | |||
*Adult-type [[body odour]] |
*Adult-type [[body odour]] |
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*Increased oiliness of skin and hair, [[Acne vulgaris|acne]] |
*Increased oiliness of skin and hair, [[Acne vulgaris|acne]] |
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*[[Pubarche]] (appearance of [[pubic hair]]) |
*[[Pubarche]] (appearance of [[pubic hair]]) |
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*[[Axillary hair]] |
*[[Axillary hair]] |
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| − | * |
+ | *Growth spurt, accelerated [[epiphysis|bone maturation]] |
| − | * |
+ | *[[Hair]] on upper lip and sideburns. |
| + | |||
| + | === Pubertal === |
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| ⚫ | |||
| ⚫ | |||
| ⚫ | |||
| ⚫ | |||
| ⚫ | |||
*[[Phallic]] enlargement or [[clitoromegaly]] |
*[[Phallic]] enlargement or [[clitoromegaly]] |
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*Increased [[libido]] and frequency of [[erection]] or clitoral engorgement |
*Increased [[libido]] and frequency of [[erection]] or clitoral engorgement |
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| − | *Pubic hair extends to thighs and up toward [[ |
+ | *Production of adult patterns of hair growth eg Pubic hair extends to thighs and up toward navel and[[Axillary hair]] appears. |
| − | *[[Facial hair]] ([[sideburns]], [[beard]], [[moustache]]) |
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| − | * Loss of scalp hair (Androgenetic Alopecia) |
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| − | *[[Chest hair]], [[periareolar]] hair, [[perianal]] hair |
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| − | *[[Leg hair]] |
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| − | *[[Axillary hair]] |
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*Subcutaneous fat in face decreases |
*Subcutaneous fat in face decreases |
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| + | *Increased muscle strength and mass<ref name="pmid8637535">{{cite journal | author = 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 = N. Engl. J. Med. | volume = 335 | issue = 1 | pages = 1–7 | year = 1996 | month = July | pmid = 8637535 | doi = 10.1056/NEJM199607043350101| url = | issn = }}</ref> |
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| − | *Increased muscle strength and mass <ref>Bhasin S, Storer TW, Berman N, ''et al''</ref> |
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*Deepening of voice |
*Deepening of voice |
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| − | *Increase in height |
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*Growth of the [[Adam's apple]] |
*Growth of the [[Adam's apple]] |
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| − | *Growth of [[spermatogenic]] tissue in |
+ | *Growth of [[spermatogenic]] tissue in testicles, male [[fertility]] |
*Growth of [[jaw]], brow, chin, nose, and remodeling of facial bone contours |
*Growth of [[jaw]], brow, chin, nose, and remodeling of facial bone contours |
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*Shoulders become broader and rib cage expands |
*Shoulders become broader and rib cage expands |
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*Completion of bone maturation and termination of growth. This occurs indirectly via [[estradiol]] [[metabolites]] and hence more gradually in men than women. |
*Completion of bone maturation and termination of growth. This occurs indirectly via [[estradiol]] [[metabolites]] and hence more gradually in men than women. |
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| − | === |
+ | === Adult === |
| ⚫ | |||
| ⚫ | |||
| ⚫ | |||
| + | |||
| − | *Regulates acute HPA response under dominance challenge<ref>P.H.Mehta, A.C. Jones, & R.A. Josephs http://homepage.psy.utexas.edu/homepage/faculty/josephs/pdf_documents/index.cfm.pdf</ref> |
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| ⚫ | |||
| + | *Regulates acute HPA ([[Hypothalamic–pituitary–adrenal axis]]) response under dominance challenge<ref name="pmid18505319">{{cite journal | author = Mehta PH, Jones AC, Josephs RA | title = The social endocrinology of dominance: basal testosterone predicts cortisol changes and behavior following victory and defeat | journal = J Pers Soc Psychol | volume = 94 | issue = 6 | pages = 1078–93 | year = 2008 | month = June | pmid = 18505319 | doi = 10.1037/0022-3514.94.6.1078 | url = http://homepage.psy.utexas.edu/homepage/faculty/josephs/pdf_documents/index.cfm.pdf | issn = }}</ref> |
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*Mental and physical energy |
*Mental and physical energy |
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| − | * |
+ | *Maintenance of muscle trophism |
| + | * In animals ([[grouse]] and [[sand lizard]]s), higher testosterone levels have been linked to a reduced [[immune system]] activity. Testosterone seems to have become part of the [[Signalling theory#Honest_signals|honest signaling]] system between potential mates in the course of evolution.<ref name="Braude_1999">{{cite journal | author = Braude S, Tang-Martinezb Z, Taylor GT | title = Stress, testosterone, and the immunoredistribution hypothesis | journal = Behavioral Ecology | volume = 10 | issue = 3 | pages = 345–350 | year = 1999 | month = March| doi = 10.1093/beheco/10.3.345| url = http://beheco.oxfordjournals.org/cgi/content/full/10/3/345 | issn = }}</ref><ref name="pmid11413653">{{cite journal | author = Olsson M, Wapstra E, Madsen T, Silverin B | title = Testosterone, ticks and travels: a test of the immunocompetence-handicap hypothesis in free-ranging male sand lizards | journal = Proc. Biol. Sci. | volume = 267 | issue = 1459 | pages = 2339–43 | year = 2000 | month = November | pmid = 11413653 | pmc = 1690810 | doi = 10.1098/rspb.2000.1289 | url = | issn = }}</ref> |
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| − | *The most recent and reliable studies have shown that testosterone does not cause [[Prostate cancer]], but that it can increase the rate of spread of any existing prostate cancer.{{Fact|date=October 2007}} Recent studies have also shown its importance in maintaining cardiovascular health. {{Fact|date=February 2008}} |
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| + | *The most recent and reliable studies have shown that testosterone does not cause or produce deleterious effects on [[prostate cancer]]. In people who have undergone testosterone deprivation therapy, testosterone increases beyond the castrate level have been shown to increase the rate of spread of an existing prostate cancer.<ref name="pmid19011298">{{cite journal | author = Morgentaler A, Schulman C | title = Testosterone and prostate safety | journal = Front Horm Res | volume = 37 | issue = | pages = 197–203 | year = 2009 | pmid = 19011298 | doi = 10.1159/000176054 | url = | issn = }}</ref><ref>{{cite journal | author = Rhoden, E.L., M.A. Averbeck, and P.E. Teloken | title = Androgen replacement in men undergoing treatment for prostate cancer | journal = J Sex Med | volume = 5 | issue = 9 | pages = 2202–8 | year = 2008 | doi = 10.1111/j.1743-6109.2008.00925.x | pmid = 18638000}}</ref><ref>{{cite journal | author = Morgentaler, A. and A.M. Traish | title = Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth | journal = Eur Urol | volume = 55 | issue = 2 | pages = 310–20 | year = 2009 | doi = 10.1016/j.eururo.2008.09.024 | pmid = 18838208}}</ref> |
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| − | *Increase [[eumelanin]] and reduce [[pheomelanin]]{{Fact|date=August 2007}} |
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| + | * Recent studies have shown conflicting results concerning the importance of testosterone in maintaining cardiovascular health.<ref name="pmid17285783">{{cite journal | author = Haddad RM, Kennedy CC, Caples SM, Tracz MJ, Boloña ER, Sideras K, Uraga MV, Erwin PJ, Montori VM | title = Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials | journal = Mayo Clin. Proc. | volume = 82 | issue = 1 | pages = 29–39 | year = 2007 | month = January | pmid = 17285783 | doi = 10.4065/82.1.29| url = | issn = }}</ref><ref name="pmid19464009">{{cite journal | author = Jones TH, Saad F | title = The effects of testosterone on risk factors for, and the mediators of, the atherosclerotic process | journal = Atherosclerosis | volume = 207| issue = 2| pages = 318–27| year = 2009 | month = April | pmid = 19464009 | doi = 10.1016/j.atherosclerosis.2009.04.016 | url = | issn = }}</ref> Nevertheless, maintaining normal testosterone levels in elderly men has been shown to improve many parameters which are thought to reduce cardiovascular disease risk, such as increased lean body mass, decreased visceral fat mass, decreased total cholesterol, and glycemic control.<ref name="pmid18488876">{{cite journal | author = Stanworth RD, Jones TH | title = Testosterone for the aging male; current evidence and recommended practice | journal = Clin Interv Aging | volume = 3 | issue = 1 | pages = 25–44 | year = 2008 | pmid = 18488876 | pmc = 2544367 | doi = | url = | issn = }}</ref> |
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| − | *Under dominance challenge, may play a role in the regulation of the [[fight-or-flight response]]<ref>P.H. Mehta & R.A. Josephs, 2006 http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WGC-4KPP4H5-1&_user=108429&_coverDate=12%2F31%2F2006&_fmt=full&_orig=search&_cdi=6819&view=c&_acct=C000059713&_version=1&_urlVersion=0&_userid=108429&md5=0b42825a9e5f21eaea7dd8ce037ffe85&ref=full</ref> |
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| + | *Under dominance challenge, may play a role in the regulation of the [[fight-or-flight response]]<ref name="pmid16928375"/> |
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| − | Testosterone regulates the population of [[Thromboxane A2|thromboxane A<sub>2</sub>]] receptors on [[megakaryocytes]] and [[platelets]] and hence platelet aggregation in humans (Ajayi and Halushka 2005, Ajayi et al. 1995). |
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| + | *Testosterone regulates the population of [[Thromboxane A2|thromboxane A<sub>2</sub>]] receptors on [[megakaryocytes]] and [[platelets]] and hence platelet aggregation in humans<ref name="pmid15820970">{{cite journal | author = Ajayi AA, Halushka PV | title = Castration reduces platelet thromboxane A2 receptor density and aggregability | journal = QJM | volume = 98 | issue = 5 | pages = 349–56 | year = 2005 | month = May | pmid = 15820970 | doi = 10.1093/qjmed/hci054 | url = | issn = }}</ref><ref name="pmid7758179">{{cite journal | author = 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 | year = 1995 | month = June | pmid = 7758179 | doi = | url = | issn = }}</ref> |
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| + | [[File:Blood values sorted by mass and molar concentration.png|thumb|center|600px|[[Reference ranges for blood tests]], showing adult male testosterone levels in light blue at center-left.]] |
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| − | In animals (grouse and sand lizards) higher testosterone levels have been linked to a reduced [[immune system]] activity. Testosterone seems to have become part of the [[Signalling theory#Honest_signals|honest signaling]] system between potential mates in the course of evolution |
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| − | <ref>{{cite web |
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| − | |url = http://beheco.oxfordjournals.org/cgi/content/full/10/3/345 |
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| − | |title=Testosterone, immunocompetence, and honest sexual signaling in male red grouse|publisher=Behavioral Ecology}}</ref><ref>{{cite web |
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| − | |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1690810 |
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| − | |title=Testosterone, tickss and travels: a test of the immunocompetence-handicap hypothesis in free-ranging male sand lizards |
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| − | |publisher=Proceedings of the Royal Society B: Biological Sciences}}</ref>. |
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| − | == |
+ | === Brain === |
| − | As testosterone affects the entire body (often by enlarging; men have bigger hearts, lungs, liver, etc.), the brain is also affected by this "sexual" advancement; the [[enzyme]] [[aromatase]] converts testosterone into [[estradiol]] that is responsible for [[masculinization]] of the brain in a male fetus. |
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| + | As testosterone affects the entire body (often by enlarging; men have bigger hearts, lungs, liver, etc.), 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 | author = Wilson JD | title = Androgens, androgen receptors, and male gender role behavior | journal = Horm Behav | volume = 40 | issue = 2 | pages = 358–66 | year = 2001 | month = September | pmid = 11534997 | doi = 10.1006/hbeh.2001.1684 | url = | issn = }}</ref> |
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| − | There are some differences in a male and female brain (the result of different testosterone levels). A clear difference is the size: the male human brain is, on average, larger; however, in females (who generally do not have as high testosterone levels) the [[corpus callosum]] is proportionally larger. This means that the effect of testosterone is a greater overall brain volume, but a decreased connection between the [[Cerebral hemisphere|hemispheres]].<ref name="Mark Solms & Oliver Turnbull"> Solms and Turnbull 2002.</ref> |
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| + | There are some 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>{{cite journal| last = Cosgrove | first = KP | coauthors = Mazure CM, Staley JK | url = http://linkinghub.elsevier.com/retrieve/pii/S0006322307001989 | title = Evolving knowledge of sex differences in brain structure, function, and chemistry. | year = 2007 | journal = Biol Psychiat | volume = 62 | pages = 847–55 | pmid = 17544382 | doi = 10.1016/j.biopsych.2007.03.001 | issue = 8 | pmc= 2711771}}</ref> In a Danish study from 2003, men were found to have a total myelinated fiber length of 176,000 km at the age of 20, whereas in women the total length was 149,000 km.<ref name="Marner">Marner L, Nyengaard JR, Tang Y, Pakkenberg B. (2003). Marked loss of myelinated nerve fibers in the human brain with age. J Comp Neurol. 462(2):144-52. {{PMID|12794739}}</ref> However, women have more dendritic connections between brain cells.<ref name = "jcn1999" >{{cite book | author = Rabinowicz T, Dean DE, Petetot JM, de Courten-Myers GM | title = Gender differences in the human cerebral cortex: more neurons in males; more processes in females. | publisher = Journal of Child Neurology| location = Lausanne, Switzerland |year = 1999 |url = http://www.ncbi.nlm.nih.gov/pubmed/10073431?dopt=Abstract }}</ref> |
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| ⚫ | |||
| ⚫ | A study conducted in 1996 found no immediate short term effects on mood or behavior from the administration of supraphysiologic doses of testosterone for 10 weeks on 43 healthy men.<ref name="pmid8637535"/> Another study found a correlation between testosterone and risk tolerance in career choice among women.<ref>[http://www.npr.org/templates/story/story.php?storyId=112334459 Testosterone Affects Some Women's Career Choices]</ref> |
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| − | The literature suggests that 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>e.g., Moffat et al, 2005; Hogervorst et al 2005.</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>e.g., Moffat and Hampson, 1996.</ref> where both hypo- and hypersecretion of circulating androgens have negative effects on cognition and cognitively-modulated aggressivity, as detailed above. |
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| + | Literature suggests that 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="pmid15582279">{{cite journal | author = Hogervorst E, Bandelow S, Combrinck M, Smith AD | title = Low free testosterone is an independent risk factor for Alzheimer's disease | journal = Exp. Gerontol. | volume = 39 | issue = 11-12 | pages = 1633–9 | year = 2004 | pmid = 15582279 | doi = 10.1016/j.exger.2004.06.019 | url = | issn = }}</ref><ref name="pmid14745052">{{cite journal | author = 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 | year = 2004 | month = January | pmid = 14745052 | doi = | url = | issn = }}</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 | author = 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 | year = 1996 | month = April | pmid = 8817730 | doi = 10.1016/0306-4530(95)00051-8 | url = | issn = }}</ref> where both hypo- and hypersecretion (over- and under-sectretion) of circulating androgens have negative effects on cognition and cognitively modulated aggressivity, as detailed above. |
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| ⚫ | Contrary to what has been postulated in outdated studies and by certain sections of the media, aggressive behaviour is not typically seen in |
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| ⚫ | Contrary to what has been postulated in outdated studies and by certain sections of the media, aggressive behaviour is not typically seen in hypogonadal men who have their testosterone replaced adequately to the eugonadal/normal range. In fact, aggressive behaviour has been associated with hypogonadism and low testosterone levels and it would seem as though supraphysiological and low levels of testosterone and [[hypogonadism]] cause [[mood disorder]]s and [[aggressive]] behaviour, with eugondal/normal testosterone levels being important for mental well-being. Testosterone depletion is a normal consequence of aging in men. One possible consequence of this could be an increased risk for the development of [[Alzheimer’s disease]].<ref name="pmid16785599">{{cite journal | author = Pike CJ, Rosario ER, Nguyen TV | title = Androgens, aging, and Alzheimer's disease | journal = Endocrine | volume = 29 | issue = 2 | pages = 233–41 | year = 2006 | month = April | pmid = 16785599 | doi = 10.1385/ENDO:29:2:233 | url = | issn = }}</ref><ref name="pmid15383512">{{cite journal | author = 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 = 1431–2 | year = 2004 | month = September | pmid = 15383512 | doi = 10.1001/jama.292.12.1431-b | url = | issn = }}</ref> |
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| ⚫ | |||
| + | == Biochemistry == |
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| − | The effects of testosterone in humans and other [[vertebrates]] occur by way of two main mechanisms: by activation of the [[androgen receptor]] (directly or as DHT), and by conversion to [[estradiol]] and activation of certain [[estrogen receptor]]s. |
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| + | === Biosynthesis === |
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| ⚫ | |||
| + | Like other [[steroid]] hormones, testosterone is derived from [[cholesterol]] (see figure to the right).<ref name="pmid1307739">{{cite journal | author = Waterman MR, Keeney DS | title = Genes involved in androgen biosynthesis and the male phenotype | journal = Horm. Res. | volume = 38 | issue = 5-6 | pages = 217–21 | year = 1992 | pmid = 1307739 | doi = 10.1159/000182546| url = | issn = }}</ref> The first step in the [[biosynthesis]] involves the oxidative cleavage of the sidechain of cholesterol by [[cholesterol side-chain cleavage enzyme|CYP11A]], 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|CYP17A]] enzyme in the [[endoplasmic reticulum]] to yield a variety of C<sub>19</sub> steroids.<ref name="pmid3535074">{{cite journal | author = 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 | year = 1986 | month = December | pmid = 3535074 | doi = 10.1126/science.3535074| url = | issn = }}</ref> In addition, the 3-hydroxyl group is oxidized by [[3-beta-HSD|3-β-HSD]] to produce [[androstenedione]]. In the final and rate limiting step, the C-17 keto group androstenedione is reduced by [[17Beta Hydroxysteroid dehydrogenase|17-β hydroxysteroid dehydrogenase]] to yield testosterone. |
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| ⚫ | 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 [[5-alpha reductase]]. DHT binds to the same androgen receptor even more strongly than T, so that its androgenic potency is about 5 times that of T.{{ |
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| + | |||
| + | The largest amounts of testosterone (>95%) are produced by the [[testis|testes]] in men.<ref name="Mooradian_ 1987"/> It is also synthesized in far smaller quantities in women by the [[thecal cells]] of the [[ovary|ovaries]], by the [[placenta]], as well as by the [[zona reticularis]] of the [[adrenal cortex]] in both sexes. In the [[testes]], testosterone is produced by the [[Leydig cell]]s.<ref name="pmid58744">{{cite journal | author = Brooks RV | title = Androgens | journal = Clin Endocrinol Metab | volume = 4 | issue = 3 | pages = 503–20 | year = 1975 | month = November | pmid = 58744 | doi = | url = | issn = }}</ref> The malegenerative 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). |
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| + | |||
| + | === Regulation === |
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| + | [[File:Hypothalamus pituitary testicles axis.png|thumb|right|200px|Hypothalamic-pituitary-testicular axis]] |
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| + | |||
| + | In males, testosterone is primarily synthesized 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 17-β hydroxysteroid dehydrogenase.<ref name="isbn0-9627422-7-9">{{cite book | author = Payne AH, O'Shaughnessy P | authorlink = | editor = Payne AH, Hardy MP, Russell LD | others = | title = Leydig Cell | edition = | language = | publisher = Cache River Press | location = Vienna [Il] | year = 1996 | origyear = | pages = 260–285 | quote = | isbn = 0-9627422-7-9 | oclc = | doi = | url = | chapter = Structure, function, and regulation of steroidogenic enzymes in the Leydig cell }}</ref> |
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| + | |||
| + | The amount of testosterone is synthesized is regulated by the [[hypothalamic-pituitary-gonadal axis|hypothalamic-pituitary-testicular axis]] (see figure to the right).<ref name="pmid1377467">{{cite journal | author = Swerdloff RS, Wang C, Bhasin S | title = Developments in the control of testicular function | journal = Baillieres Clin. Endocrinol. Metab. | volume = 6 | issue = 2 | pages = 451–83 | year = 1992 | month = April | pmid = 1377467 | doi = | url = | issn = }}</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 later two hormones stimulate the testis to synthesize testosterone. Finally increasing levels of testosterone through a in a negative [[feedback]] loop act on the hypothalamus and pituitary to inhibit the release of GnRH and FSH/LH respectively. |
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| + | |||
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| + | * Loss of status or dominance in men may result in a decreased testosterone level.<ref name="pmid16928375">{{cite journal | author = Mehta PH, Josephs RA | title = Testosterone change after losing predicts the decision to compete again | journal = Horm Behav | volume = 50 | issue = 5 | pages = 684–92 | year = 2006 | month = December | pmid = 16928375 | doi = 10.1016/j.yhbeh.2006.07.001 | url = | issn = }}</ref> |
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| + | * Implicit power motivation predicts an increased testosterone release in men.<ref name="pmid10603287">{{cite journal | author = Schultheiss OC, Campbell KL, McClelland DC | title = Implicit power motivation moderates men's testosterone responses to imagined and real dominance success | journal = Horm Behav | volume = 36 | issue = 3 | pages = 234–41 | year = 1999 | month = December | pmid = 10603287 | doi = 10.1006/hbeh.1999.1542 | url = | issn = }}</ref> |
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| + | * Aging reduces testosterone release.<ref name="pmid16339924">{{cite journal | author = Liu PY, Pincus SM, Takahashi PY, Roebuck PD, Iranmanesh A, Keenan DM, Veldhuis JD | title = Aging attenuates both the regularity and joint synchrony of LH and testosterone secretion in normal men: analyses via a model of graded GnRH receptor blockade | journal = Am. J. Physiol. Endocrinol. Metab. | volume = 290 | issue = 1 | pages = E34–E41 | year = 2006 | month = January | pmid = 16339924 | doi = 10.1152/ajpendo.00227.2005 | url = | issn = }}</ref> |
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| + | * Sleep ([[REM dream]]) increases nocturnal testosterone levels.<ref name="pmid18519168">{{cite journal | author = 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 Med Rev | volume = 12 | issue = 5 | pages = 365–79 | year = 2008 | month = October | pmid = 18519168 | doi = 10.1016/j.smrv.2007.12.003 | url = http://www.sono.org.br/pdf/2008_Andersen_Sleep_Med_Rev.pdf | issn = }}</ref> |
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| + | * [[Resistance training]] increases testosterone levels,<ref name="url_Marin">{{cite journal | author = Marin DP, Figueira AJ Junior, Pinto LG | year = | month = | title = One session of resistance training may increase serum testosterone and triiodetironine in young men| url = http://journals.lww.com/acsm-msse/Fulltext/2006/05001/One_Session_of_Resistance_Training_May_Increase.2108.aspx| journal = Medicine & Science in Sports & Exercise | volume = 38 | issue = 5 | page = S285 | doi = }}</ref> however, in older men, that increase can be avoided by protein ingestion.<ref name="pmid18455389">{{cite journal | author = 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 = J. Steroid Biochem. Mol. Biol. | volume = 110 | issue = 1-2 | pages = 130–7 | year = 2008 | month = May | pmid = 18455389 | doi = 10.1016/j.jsbmb.2008.03.030 | url = | issn = }}</ref> |
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| + | * [[Zinc]] deficiency lowers testosterone levels<ref name="pmid8875519">{{cite journal | author = 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 = 344–8 | year = 1996 | month = May | pmid = 8875519 | doi = 10.1016/S0899-9007(96)80058-X| url = | issn = }}</ref> but over supplementation has no effect on serum testosterone.<ref name="pmid17882141">{{cite journal | author = 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 = Eur J Clin Nutr | volume = 63 | issue = 1 | pages = 65–70 | year = 2009 | month = January | pmid = 17882141 | doi = 10.1038/sj.ejcn.1602899 | url = | issn = }}</ref> |
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| + | *[[Licorice]]. The active ingredient in licorice root, [[glycyrrhizinic acid]] has been linked to small, clinically non-significant decreases in testosterone levels.<ref name="pmid11716893">{{cite journal | author = Josephs RA, Guinn JS, Harper ML, Askari F | title = Liquorice consumption and salivary testosterone concentrations | journal = Lancet | volume = 358 | issue = 9293 | pages = 1613–4 | year = 2001 | month = November | pmid = 11716893 | doi = 10.1016/S0140-6736(01)06664-8 | url = | issn = }}</ref> In contrast, a more recent study found that licorice administration produced a substantial testosterone decrease in a small, female-only sample.<ref name="pmid15579328">{{cite journal | author = Armanini D, Mattarello MJ, Fiore C, Bonanni G, Scaroni C, Sartorato P, Palermo M | title = Licorice reduces serum testosterone in healthy women | journal = Steroids | volume = 69 | issue = 11-12 | pages = 763–6 | year = 2004 | pmid = 15579328 | doi = 10.1016/j.steroids.2004.09.005 | url = | issn = }}</ref> |
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| + | |||
| + | === Metabolism === |
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| + | |||
| + | Approximately 7% of testosterone is reduced to 5α-[[dihydrotestosterone]] (DHT) by the cytochrome P<sub>450</sub> enzyme [[5-alpha reductase|5α-reductase]],<ref name="pmid8092979">{{cite journal | author = Randall VA | title = Role of 5 alpha-reductase in health and disease | journal = Baillieres Clin. Endocrinol. Metab. | volume = 8 | issue = 2 | pages = 405–31 | year = 1994 | month = April | pmid = 8092979 | doi = 10.1016/S0950-351X(05)80259-9| url = | issn = }}</ref> an enzyme highly expressed in male accessory sex organs and hair follicles.<ref name="Mooradian_ 1987"/> Approximately 0.3% of testosterone is converted into estradiol by [[aromatase]] (CYP19A1)<ref name="pmid12428207">{{cite journal | author = Meinhardt U, Mullis PE | title = The essential role of the aromatase/p450arom | journal = Semin. Reprod. Med. | volume = 20 | issue = 3 | pages = 277–84 | year = 2002 | month = August | pmid = 12428207 | doi = 10.1055/s-2002-35374 | url = | issn = }}</ref> an enzyme expressed in the brain, liver, and adipose tissues.<ref name="Mooradian_ 1987"/> |
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| + | |||
| + | DHT is a more potent form of testosterone while estradiol has completely different activities (feminization) compared to testosterone (masculinization). Finally testosterone and DHT may be deactivated or cleared by enzymes that hydroxylate at the 6, 7, 15 or 16 positions.<ref name="isbn0-7216-5944-6">{{cite book | author = Trager L | authorlink = | editor = | others = | title = Steroidhormone: Biosynthese, Stoffwechsel, Wirkung | edition = | language = German | publisher = Springer-Verlag | location = | year = 1977 | origyear = | pages = 349 | quote = | isbn = | oclc = | doi = 0387080120 | url = | accessdate = }}</ref> |
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| + | |||
| ⚫ | |||
| + | |||
| + | The effects of testosterone in humans and other [[vertebrates]] occur by way of two main 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 | author = Hiipakka RA, Liao S | title = Molecular mechanism of androgen action |journal = Trends Endocrinol. Metab. | volume = 9 | issue = 8 | pages = 317–24 | year = 1998 | month = October | pmid = 18406296 | doi = 10.1016/S1043-2760(98)00081-2| url = | issn =}}</ref><ref name="pmid11511858">{{cite journal | author = McPhaul MJ, Young M | title = Complexities of androgen action | journal = J. Am. Acad. Dermatol. | volume = 45 | issue = 3 Suppl | pages = S87–94 | year = 2001 | month = September | pmid = 11511858 | doi = 10.1067/mjd.2001.117429| url = | issn = }}</ref> |
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| ⚫ | 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 [[5-alpha reductase]]. DHT binds to the same androgen receptor even more strongly than T, so that its androgenic potency is about 5 times that of T.<ref name="pmid3762019">{{cite journal | author = Breiner M, Romalo G, Schweikert HU | title = Inhibition of androgen receptor binding by natural and synthetic steroids in cultured human genital skin fibroblasts | journal = Klin. Wochenschr. | volume = 64 | issue = 16 | pages = 732–7 | year = 1986 | month = August | pmid = 3762019 | doi = 10.1007/BF01734339 | url = | issn = }}</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. It is important to note that if there is a 5-alpha reductase deficiency,<!-- in the womb? during childhood? --> the body (of a human) will ''continue'' growing into a female with testicles. |
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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 biological [[sexual differentiation|differences]] between males and females. |
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 biological [[sexual differentiation|differences]] between males and females. |
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| − | ==Changes during aging== |
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| − | Testosterone levels decline gradually with age in human beings. The clinical significance of this decrease is debated (see [[andropause]]). There is disagreement about if and when to treat aging men with testosterone replacement therapy. The [[American Society of Andrology]]'s position is that testosterone therapy "is indicated when both clinical symptoms and signs suggestive of [[Hypogonadism|androgen deficiency]] and decreased testosterone levels are present". The American Association of Clinical Endocrinologists says "[[Hypogonadism]] is defined as a free testosterone level that is below the lower limit of normal for young adult control subjects. Previously, age-related decreases in free testosterone were once accepted as normal. Currently, they are not considered normal. Patients with low-normal to subnormal range testosterone levels warrant a clinical trial of testosterone."<ref>{{cite web |
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| − | |url = http://www.aace.com/pub/pdf/guidelines/sexdysguid.pdf |
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| − | |format=PDF|title = Medical guidelines for clinical practice for the evaluation and treatment of male sexual dysfunction |
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| − | |publisher = American association of clinical endocrinologists}}</ref> |
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| − | There isn't total agreement on the threshold of testosterone value below which a man would be considered [[hypogonadal]]. (Currently there are no standards as to when to treat women.) Testosterone can be measured as "free" (that is, bioavailable and unbound) or more commonly, "total" (including the percentage which is chemically bound and unavailable). In the United States, male total testosterone levels below 300 to 400 ng/dl from a morning sample |
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| − | {{Vague|urine?|date=November 2008}} |
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| − | are generally considered low. {{Fact|date=May 2008}} However these numbers are typically not age-adjusted, but based on an average of a test group which includes elderly males with low testosterone levels. {{Fact|date=May 2008}} Therefore a value of 300 ng/dl might be normal for a 65-year-old male, but not normal for a 30-year-old. {{Fact|date=May 2008}} Identification of inadequate testosterone in an aging male by symptoms alone can be difficult. The signs and symptoms are non-specific, and might be confused with normal aging characteristics, such as loss of muscle mass and bone density, decreased physical endurance, decreased memory ability {{Fact|date=May 2008}} and loss of libido. |
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| − | Replacement therapy can take the form of injectable depots, transdermal patches and gels, subcutaneous pellets and oral therapy. Adverse effects of testosterone supplementation include minor side effects such as acne and oily skin, and more significant complications such as increased [[hematocrit]] which can require [[venipuncture]] in order to treat, exacerbation of [[sleep apnea]] and acceleration of pre-existing [[prostate cancer]] growth. Exogenous testosterone also causes suppression of [[spermatogenesis]] and can lead to infertility.<ref name="Lancet">World Health Organisation (1990), The Lancet.</ref> |
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| − | It is recommended that physicians screen for prostate cancer with a digital rectal exam and PSA ([[prostate specific antigen]]) level prior to initiating therapy, and monitor hematocrit and PSA levels closely during therapy. |
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| − | ===Benefits=== |
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| − | Appropriate testosterone therapy can prevent or reduce the likelihood of [[osteoporosis]], [[type 2 diabetes]], [[cardio-vascular disease]] (CVD), [[obesity]], [[Major depressive episode|depression]] and anxiety and the statistical risk of early mortality. Low testosterone also brings with it an increased risk for the development of [[Alzheimer’s Disease]] (Pike et al., 2006, Rosario 2004). |
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| − | A small trial in 2005 showed mixed results.<ref>http://www.ncbi.nlm.nih.gov/pubmed/18167405 "Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial."</ref> |
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| − | Large scale trials to assess the efficiency and long-term safety of testosterone are still lacking.<ref>http://www.endocrinetoday.com/view.aspx?rid=29171 "Testosterone treatment in aging men"</ref> |
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==See also== |
==See also== |
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{{Cholesterol and steroid intermediates}} |
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Revision as of 14:26, 6 September 2012
Assessment |
Biopsychology |
Comparative |
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Personality |
Philosophy |
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World psychology |
Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)
|
Testosterone chemical structure | |
| (8R,9S,10R,13S,14S,17S)- 17-hydroxy-10,13-dimethyl- 1,2,6,7,8,9,11,12,14,15,16,17- dodecahydrocyclopenta[a]phenanthren-3-one IUPAC name | |
| CAS number 58-22-0 |
ATC code G03BA03 |
| PubChem 6013 |
DrugBank DB00624 |
| Chemical formula | {{{chemical_formula}}} |
| Molecular weight | 288.42 |
| Bioavailability | low (due to extensive first pass metabolism) |
| Metabolism | Liver, Testis and Prostate |
| Elimination half-life | 2-4 hours |
| Excretion | Urine (90%), feces (6%) |
| Pregnancy category | X (USA), Teratogenic effects |
| Legal status | Schedule III (USA) Schedule IV (Canada) |
| Routes of administration | Intramuscular injection, transdermal (cream, gel, or patch), sub-'Q' pellet |
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles,[1] birds,[2] and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands. It is the principal male sex hormone and an anabolic steroid.
In men, testosterone plays a key role in the development of male reproductive tissues such as the testis and prostate as well as promoting secondary sexual characteristics such as increased muscle, bone mass and hair growth.[3] In addition, testosterone is essential for health and well-being[4] as well as the prevention of osteoporosis.[5]
On average, an adult human male body produces about ten times more testosterone than an adult human female body, but females are, from a behavioral perspective (rather than from an anatomical or biological perspective [citation needed]), more sensitive to the hormone.[6] However, the overall ranges for male and female are very wide, such that the ranges actually overlap at the low end and high end respectively [citation needed].
Testosterone is conserved through most vertebrates, although fish make a slightly different form called 11-ketotestosterone.[7] Its counterpart in insects is ecdysone.[8] These ubiquitous steroids suggest that sex hormones have an ancient evolutionary history.[9]
Of interest to psychologists are:
The link between testosterone and thoughts, feelings and behavior
Testosterone has been associated with a broad array of psychological effects.
Testosterone and human relationships
- Studies show that falling in love decreases men's testosterone levels while increasing women's testosterone levels. It is speculated that these changes in testosterone result in the temporary reduction of differences in behavior between the sexes.[10]
Testosterone and risk taking
- Recent studies suggest that testosterone level plays a major role in risk-taking during financial decisions.[11][12]
- Fatherhood also decreases testosterone levels in men, suggesting that the resulting emotional and behavioral changes promote paternal care.[13]
Testosterone and aggression
- Main article: Testosterone and aggression
There is strong evidence in animals that testosterone is directly associated with aggression, although this correlation is not as strong in humans.[14] In human studies a relationship has been found between measures of testosterone in adolescent males and aggression [15] with similar results found in women [16].
Testosterone and sexuality
- Main article: Testosterone and sexual arousal
Testosterone and social dominance
Testosterone and mental disorders
Physiological effects
In general, androgens promote protein synthesis and growth of those tissues with androgen receptors. Testosterone effects can be classified as virilizing and anabolic, although the distinction is somewhat artificial, as many of the effects can be considered both. Testosterone is anabolic, meaning it builds up bone and muscle mass.
- Anabolic effects include growth of muscle mass and strength, increased bone density and strength, and stimulation of linear growth and bone maturation.
- Androgenic effects include maturation of the sex organs, particularly the penis and the formation of the scrotum in the fetus, and after birth (usually at puberty) a deepening of the voice, growth of the beard and axillary hair. Many of these fall into the category of male secondary sex characteristics.
Testosterone effects can also be classified by the age of usual occurrence. For postnatal effects in both males and females, these are mostly dependent on the levels and duration of circulating free testosterone.
Prenatal
Most of the prenatal androgen effects occur between 7 and 12 weeks of the gestation.
- Genital virilization (midline fusion, phallic urethra, scrotal thinning and rugation, phallic enlargement); although the role of testosterone is far smaller than that of Dihydrotestosterone.
- Development of prostate and seminal vesicles
- Gender identity[17]
Early infancy
Early infancy androgen effects are the least understood. In the first weeks of life for male infants, testosterone levels rise. The levels remain in a pubertal range for a few months, but usually reach the barely detectable levels of childhood by 4–6 months of age.[18][19] The function of this rise in humans is unknown. It has been speculated that "brain masculinization" is occurring since no significant changes have been identified in other parts of the body.[20][citation needed] Surprisingly, the male brain is masculinized by testosterone being aromatized into estrogen, which crosses the blood-brain barrier and enters the male brain, whereas female fetuses have alpha-fetoprotein which binds up the estrogen so that female brains are not affected.[21]
Pre-peripubertal
Pre- Peripubertal effects are the first observable effects of rising androgen levels at the end of childhood, occurring in both boys and girls. [vague]
- Adult-type body odour
- Increased oiliness of skin and hair, acne
- Pubarche (appearance of pubic hair)
- Axillary hair
- Growth spurt, accelerated bone maturation
- Hair on upper lip and sideburns.
Pubertal
Pubertal effects begin to occur when androgen has been higher than normal adult female levels for months or years. In males, these are usual late pubertal effects, and occur in women after prolonged periods of heightened levels of free testosterone in the blood.
- Enlargement of sebaceous glands. This might cause acne.
- Phallic enlargement or clitoromegaly
- Increased libido and frequency of erection or clitoral engorgement
- Production of adult patterns of hair growth eg Pubic hair extends to thighs and up toward navel andAxillary hair appears.
- Subcutaneous fat in face decreases
- Increased muscle strength and mass[22]
- Deepening of voice
- Growth of the Adam's apple
- Growth of spermatogenic tissue in testicles, male fertility
- Growth of jaw, brow, chin, nose, and remodeling of facial bone contours
- Shoulders become broader and rib cage expands
- Completion of bone maturation and termination of growth. This occurs indirectly via estradiol metabolites and hence more gradually in men than women.
Adult
Adult testosterone effects are more clearly demonstrable in males than in females, but are likely important to both sexes. Some of these effects may decline as testosterone levels decrease in the later decades of adult life.
- Libido and clitoral engorgement/penile erection frequency
- Regulates acute HPA (Hypothalamic–pituitary–adrenal axis) response under dominance challenge[23]
- Mental and physical energy
- Maintenance of muscle trophism
- In animals (grouse and sand lizards), higher testosterone levels have been linked to a reduced immune system activity. Testosterone seems to have become part of the honest signaling system between potential mates in the course of evolution.[24][25]
- The most recent and reliable studies have shown that testosterone does not cause or produce deleterious effects on prostate cancer. In people who have undergone testosterone deprivation therapy, testosterone increases beyond the castrate level have been shown to increase the rate of spread of an existing prostate cancer.[26][27][28]
- Recent studies have shown conflicting results concerning the importance of testosterone in maintaining cardiovascular health.[29][30] Nevertheless, maintaining normal testosterone levels in elderly men has been shown to improve many parameters which are thought to reduce cardiovascular disease risk, such as increased lean body mass, decreased visceral fat mass, decreased total cholesterol, and glycemic control.[31]
- Under dominance challenge, may play a role in the regulation of the fight-or-flight response[32]
- Testosterone regulates the population of thromboxane A2 receptors on megakaryocytes and platelets and hence platelet aggregation in humans[33][34]
Reference ranges for blood tests, showing adult male testosterone levels in light blue at center-left.
- Testosterone is necessary for normal sperm development. It activates genes in Sertoli cells, which promote differentiation of spermatogonia.
Brain
As testosterone affects the entire body (often by enlarging; men have bigger hearts, lungs, liver, etc.), the brain is also affected by this "sexual" differentiation;[17] 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 diseases of androgen formation or androgen receptor function, to be associated with functional androgen receptors.[35]
There are some 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.[36] In a Danish study from 2003, men were found to have a total myelinated fiber length of 176,000 km at the age of 20, whereas in women the total length was 149,000 km.[37] However, women have more dendritic connections between brain cells.[38]
A study conducted in 1996 found no immediate short term effects on mood or behavior from the administration of supraphysiologic doses of testosterone for 10 weeks on 43 healthy men.[22] Another study found a correlation between testosterone and risk tolerance in career choice among women.[39]
Literature suggests that 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,[40][41] 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,[42] where both hypo- and hypersecretion (over- and under-sectretion) of circulating androgens have negative effects on cognition and cognitively modulated aggressivity, as detailed above.
Contrary to what has been postulated in outdated studies and by certain sections of the media, aggressive behaviour is not typically seen in hypogonadal men who have their testosterone replaced adequately to the eugonadal/normal range. In fact, aggressive behaviour has been associated with hypogonadism and low testosterone levels and it would seem as though supraphysiological and low levels of testosterone and hypogonadism cause mood disorders and aggressive behaviour, with eugondal/normal testosterone levels being important for mental well-being. Testosterone depletion is a normal consequence of aging in men. One possible consequence of this could be an increased risk for the development of Alzheimer’s disease.[43][44]
Biochemistry
Biosynthesis
Human steroidogenesis, showing testosterone near bottom.
Like other steroid hormones, testosterone is derived from cholesterol (see figure to the right).[45] The first step in the biosynthesis involves the oxidative cleavage of the sidechain of cholesterol by CYP11A, a 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 CYP17A enzyme in the endoplasmic reticulum to yield a variety of C19 steroids.[46] In addition, the 3-hydroxyl group is oxidized by 3-β-HSD to produce androstenedione. In the final and rate limiting step, the C-17 keto group androstenedione is reduced by 17-β hydroxysteroid dehydrogenase to yield testosterone.
The largest amounts of testosterone (>95%) are produced by the testes in men.[3] It is also synthesized in far smaller quantities in women by the thecal cells of the ovaries, by the placenta, as well as by the zona reticularis of the adrenal cortex in both sexes. In the testes, testosterone is produced by the Leydig cells.[47] The malegenerative glands also contain Sertoli cells 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
Hypothalamic-pituitary-testicular axis
In males, testosterone is primarily synthesized 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 17-β hydroxysteroid dehydrogenase.[48]
The amount of testosterone is synthesized is regulated by the hypothalamic-pituitary-testicular axis (see figure to the right).[49] When testosterone levels are low, gonadotropin-releasing hormone (GnRH) is released by the hypothalamus which in turn stimulates the pituitary gland to release FSH and LH. These later two hormones stimulate the testis to synthesize testosterone. Finally increasing levels of testosterone through a in a negative feedback loop act on the hypothalamus and pituitary to inhibit the release of GnRH and FSH/LH respectively.
Environmental factors affecting testosterone levels include:
- Loss of status or dominance in men may result in a decreased testosterone level.[32]
- Implicit power motivation predicts an increased testosterone release in men.[50]
- Aging reduces testosterone release.[51]
- Hypogonadism
- Sleep (REM dream) increases nocturnal testosterone levels.[52]
- Resistance training increases testosterone levels,[53] however, in older men, that increase can be avoided by protein ingestion.[54]
- Zinc deficiency lowers testosterone levels[55] but over supplementation has no effect on serum testosterone.[56]
- Licorice. The active ingredient in licorice root, glycyrrhizinic acid has been linked to small, clinically non-significant decreases in testosterone levels.[57] In contrast, a more recent study found that licorice administration produced a substantial testosterone decrease in a small, female-only sample.[58]
Metabolism
Approximately 7% of testosterone is reduced to 5α-dihydrotestosterone (DHT) by the cytochrome P450 enzyme 5α-reductase,[59] an enzyme highly expressed in male accessory sex organs and hair follicles.[3] Approximately 0.3% of testosterone is converted into estradiol by aromatase (CYP19A1)[60] an enzyme expressed in the brain, liver, and adipose tissues.[3]
DHT is a more potent form of testosterone while estradiol has completely different activities (feminization) compared to testosterone (masculinization). Finally testosterone and DHT may be deactivated or cleared by enzymes that hydroxylate at the 6, 7, 15 or 16 positions.[61]
Mechanism of action
The effects of testosterone in humans and other vertebrates occur by way of two main mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors.[62][63]
Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5-alpha reductase. DHT binds to the same androgen receptor even more strongly than T, so that its androgenic potency is about 5 times that of T.[64] 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 chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects. It is important to note that if there is a 5-alpha reductase deficiency, the body (of a human) will continue growing into a female with testicles.
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 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 maturation of cartilage into bone, leading to closure of the 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 LH secretion). In many mammals, prenatal or perinatal "masculinization" of the sexually dimorphic areas of the brain by estradiol derived from testosterone programs later male sexual behavior.
The human hormone testosterone is produced in greater amounts by males, and less by females. The human hormone estrogen is produced in greater amounts by females, and less by males. Testosterone causes the appearance of masculine traits (i.e., deepening voice, pubic and facial hairs, muscular build, etc.) Like men, women rely on testosterone to maintain libido, bone density and muscle mass throughout their lives. In men, inappropriately high levels of estrogens lower testosterone, decrease muscle mass, stunt growth in teenagers, introduce gynecomastia, increase feminine characteristics, and decrease susceptibility to prostate cancer, reduces libido and causes erectile dysfunction and can cause excessive sweating and hot flushes. However, an appropriate amount of estrogens is required in the male in order to ensure well-being, bone density, libido, erectile function, etc.
Therapeutic use
- Main article: Testosterone therapy
Testosterone therapy is a form of hormone therapy in which testosterone is administered to supplement existing low level of the hormone.
See also
- Fetal testosterone theory of autism
- Male
- Testosterone poisoning
- Testosterone spray
Notes
- ↑ Cox RM, John-Alder HB (December 2005). Testosterone has opposite effects on male growth in lizards (Sceloporus spp.) with opposite patterns of sexual size dimorphism. J. Exp. Biol. 208 (Pt 24): 4679–87.
- ↑ Reed WL, Clark ME, Parker PG, Raouf SA, Arguedas N, Monk DS, Snajdr E, Nolan V, Ketterson ED (May 2006). Physiological effects on demography: a long-term experimental study of testosterone's effects on fitness. Am. Nat. 167 (5): 667–83.
- ↑ 3.0 3.1 3.2 3.3 Mooradian AD, Morley JE, Korenman SG (February 1987). Biological actions of androgens. Endocr. Rev. 8 (1): 1–28.
- ↑ Bassil N, Alkaade S, Morley JE (June 2009). The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag 5 (3): 427–48.
- ↑ Tuck SP, Francis RM (2009). Testosterone, bone and osteoporosis. Front Horm Res 37: 123–32.
- ↑ Dabbs M, Dabbs JM (2000). Heroes, rogues, and lovers: testosterone and behavior, New York: McGraw-Hill.
- ↑ Nelson, Randy F. (2005). An introduction to behavioral endocrinology, 143, Sunderland, Mass: Sinauer Associates.
- ↑ De Loof A (October 2006). Ecdysteroids: the overlooked sex steroids of insects? Males: the black box. Insect Science 13 (5): 325–338.
- ↑ Mechoulam R, Brueggemeier RW, Denlinger DL (September 1984). Estrogens in insects. Journal Cellular and Molecular Life Sciences 40 (9): 942–944.
- ↑ Marazziti D, Canale D. 2004.Hormonal changes when falling in love. Psychoneuroendocrinology 29(7): 931-936.
- ↑ Sapienza P, Zingales L, Maestripieri D (September 2009). Gender differences in financial risk aversion and career choices are affected by testosterone. Proc. Natl. Acad. Sci. U.S.A. 106 (36): 15268–73.
- ↑ Apicella CL, Dreber A, Campbell B, Gray PB, Hoffman M, Little AC (November 2008). Testosterone and financial risk preferences. Evolution and Human Behavior 29 (6): 384–390.
- ↑ Berg SJ, Wynne-Edwards KE. 2001. Changes in testosterone, cortisol, and estradiol levels in men becoming fathers. Mayo Clinic Proceedings 76(1): 582-592.
- ↑ Simpson, K (2001) The role of testosterone in aggression. MJM, 6, 32-40 Full text
- ↑ Olweus D, Mattson A, Schalling D, Low H. (1988) Circulating testosterone levels and aggression in adolescent males: a causal analysis. Psychosomatic Medicine 50: 261-272.
- ↑ Ehlers CL, Rickler KC, Hovey JE. (1980) A possible relationship between plasma testosterone and aggressive behavior and socialdominance in man. Psychosomatic Medicine 36: 469-475
- ↑ 17.0 17.1 Swaab DF, Garcia-Falgueras A (2009). Sexual differentiation of the human brain in relation to gender identity and sexual orientation. Funct. Neurol. 24 (1): 17–28.
- ↑ Forest MG, Cathiard AM, Bertrand JA (July 1973). Evidence of testicular activity in early infancy. J. Clin. Endocrinol. Metab. 37 (1): 148–51.
- ↑ Corbier P, Edwards DA, Roffi J (1992). The neonatal testosterone surge: a comparative study. Arch Int Physiol Biochim Biophys 100 (2): 127–31.
- ↑ Dakin CL, Wilson CA, Kalló I, Coen CW, Davies DC (May 2008). Neonatal stimulation of 5-HT(2) receptors reduces androgen receptor expression in the rat anteroventral periventricular nucleus and sexually dimorphic preoptic area. Eur. J. Neurosci. 27 (9): 2473–80.
- ↑ http://homepage.psy.utexas.edu/homepage/class/psy308/Humm/ReviewofSexualDifferentiation
- ↑ 22.0 22.1 Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi A, Casaburi R (July 1996). The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N. Engl. J. Med. 335 (1): 1–7.
- ↑ Mehta PH, Jones AC, Josephs RA (June 2008). The social endocrinology of dominance: basal testosterone predicts cortisol changes and behavior following victory and defeat. J Pers Soc Psychol 94 (6): 1078–93.
- ↑ Braude S, Tang-Martinezb Z, Taylor GT (March 1999). Stress, testosterone, and the immunoredistribution hypothesis. Behavioral Ecology 10 (3): 345–350.
- ↑ Olsson M, Wapstra E, Madsen T, Silverin B (November 2000). Testosterone, ticks and travels: a test of the immunocompetence-handicap hypothesis in free-ranging male sand lizards. Proc. Biol. Sci. 267 (1459): 2339–43.
- ↑ Morgentaler A, Schulman C (2009). Testosterone and prostate safety. Front Horm Res 37: 197–203.
- ↑ Rhoden, E.L., M.A. Averbeck, and P.E. Teloken (2008). Androgen replacement in men undergoing treatment for prostate cancer. J Sex Med 5 (9): 2202–8.
- ↑ Morgentaler, A. and A.M. Traish (2009). Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol 55 (2): 310–20.
- ↑ Haddad RM, Kennedy CC, Caples SM, Tracz MJ, Boloña ER, Sideras K, Uraga MV, Erwin PJ, Montori VM (January 2007). Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin. Proc. 82 (1): 29–39.
- ↑ Jones TH, Saad F (April 2009). The effects of testosterone on risk factors for, and the mediators of, the atherosclerotic process. Atherosclerosis 207 (2): 318–27.
- ↑ Stanworth RD, Jones TH (2008). Testosterone for the aging male; current evidence and recommended practice. Clin Interv Aging 3 (1): 25–44.
- ↑ 32.0 32.1 Mehta PH, Josephs RA (December 2006). Testosterone change after losing predicts the decision to compete again. Horm Behav 50 (5): 684–92.
- ↑ Ajayi AA, Halushka PV (May 2005). Castration reduces platelet thromboxane A2 receptor density and aggregability. QJM 98 (5): 349–56.
- ↑ Ajayi AA, Mathur R, Halushka PV (June 1995). Testosterone increases human platelet thromboxane A2 receptor density and aggregation responses. Circulation 91 (11): 2742–7.
- ↑ Wilson JD (September 2001). Androgens, androgen receptors, and male gender role behavior. Horm Behav 40 (2): 358–66.
- ↑ Cosgrove, KP, Mazure CM, Staley JK (2007). Evolving knowledge of sex differences in brain structure, function, and chemistry.. Biol Psychiat 62 (8): 847–55.
- ↑ Marner L, Nyengaard JR, Tang Y, Pakkenberg B. (2003). Marked loss of myelinated nerve fibers in the human brain with age. J Comp Neurol. 462(2):144-52. PMID 12794739
- ↑ Rabinowicz T, Dean DE, Petetot JM, de Courten-Myers GM (1999). Gender differences in the human cerebral cortex: more neurons in males; more processes in females., Lausanne, Switzerland: Journal of Child Neurology.
- ↑ Testosterone Affects Some Women's Career Choices
- ↑ Hogervorst E, Bandelow S, Combrinck M, Smith AD (2004). Low free testosterone is an independent risk factor for Alzheimer's disease. Exp. Gerontol. 39 (11-12): 1633–9.
- ↑ Moffat SD, Zonderman AB, Metter EJ, Kawas C, Blackman MR, Harman SM, Resnick SM (January 2004). Free testosterone and risk for Alzheimer disease in older men. Neurology 62 (2): 188–93.
- ↑ Moffat SD, Hampson E (April 1996). A curvilinear relationship between testosterone and spatial cognition in humans: possible influence of hand preference. Psychoneuroendocrinology 21 (3): 323–37.
- ↑ Pike CJ, Rosario ER, Nguyen TV (April 2006). Androgens, aging, and Alzheimer's disease. Endocrine 29 (2): 233–41.
- ↑ Rosario ER, Chang L, Stanczyk FZ, Pike CJ (September 2004). Age-related testosterone depletion and the development of Alzheimer disease. JAMA 292 (12): 1431–2.
- ↑ Waterman MR, Keeney DS (1992). Genes involved in androgen biosynthesis and the male phenotype. Horm. Res. 38 (5-6): 217–21.
- ↑ Zuber MX, Simpson ER, Waterman MR (December 1986). Expression of bovine 17 alpha-hydroxylase cytochrome P-450 cDNA in nonsteroidogenic (COS 1) cells. Science 234 (4781): 1258–61.
- ↑ Brooks RV (November 1975). Androgens. Clin Endocrinol Metab 4 (3): 503–20.
- ↑ Payne AH, O'Shaughnessy P (1996). "Structure, function, and regulation of steroidogenic enzymes in the Leydig cell" Payne AH, Hardy MP, Russell LD Leydig Cell, 260–285, Vienna [Il]: Cache River Press.
- ↑ Swerdloff RS, Wang C, Bhasin S (April 1992). Developments in the control of testicular function. Baillieres Clin. Endocrinol. Metab. 6 (2): 451–83.
- ↑ Schultheiss OC, Campbell KL, McClelland DC (December 1999). Implicit power motivation moderates men's testosterone responses to imagined and real dominance success. Horm Behav 36 (3): 234–41.
- ↑ Liu PY, Pincus SM, Takahashi PY, Roebuck PD, Iranmanesh A, Keenan DM, Veldhuis JD (January 2006). Aging attenuates both the regularity and joint synchrony of LH and testosterone secretion in normal men: analyses via a model of graded GnRH receptor blockade. Am. J. Physiol. Endocrinol. Metab. 290 (1): E34–E41.
- ↑ Andersen ML, Tufik S (October 2008). The effects of testosterone on sleep and sleep-disordered breathing in men: its bidirectional interaction with erectile function. Sleep Med Rev 12 (5): 365–79.
- ↑ Marin DP, Figueira AJ Junior, Pinto LG. One session of resistance training may increase serum testosterone and triiodetironine in young men. Medicine & Science in Sports & Exercise 38 (5).
- ↑ Hulmi JJ, Ahtiainen JP, Selänne H, Volek JS, Häkkinen K, Kovanen V, Mero AA (May 2008). Androgen receptors and testosterone in men--effects of protein ingestion, resistance exercise and fiber type. J. Steroid Biochem. Mol. Biol. 110 (1-2): 130–7.
- ↑ Prasad AS, Mantzoros CS, Beck FW, Hess JW, Brewer GJ (May 1996). Zinc status and serum testosterone levels of healthy adults. Nutrition 12 (5): 344–8.
- ↑ Koehler K, Parr MK, Geyer H, Mester J, Schänzer W (January 2009). Serum testosterone and urinary excretion of steroid hormone metabolites after administration of a high-dose zinc supplement. Eur J Clin Nutr 63 (1): 65–70.
- ↑ Josephs RA, Guinn JS, Harper ML, Askari F (November 2001). Liquorice consumption and salivary testosterone concentrations. Lancet 358 (9293): 1613–4.
- ↑ Armanini D, Mattarello MJ, Fiore C, Bonanni G, Scaroni C, Sartorato P, Palermo M (2004). Licorice reduces serum testosterone in healthy women. Steroids 69 (11-12): 763–6.
- ↑ Randall VA (April 1994). Role of 5 alpha-reductase in health and disease. Baillieres Clin. Endocrinol. Metab. 8 (2): 405–31.
- ↑ Meinhardt U, Mullis PE (August 2002). The essential role of the aromatase/p450arom. Semin. Reprod. Med. 20 (3): 277–84.
- ↑ Trager L (1977). Steroidhormone: Biosynthese, Stoffwechsel, Wirkung (in German), 349, Springer-Verlag.
- ↑ Hiipakka RA, Liao S (October 1998). Molecular mechanism of androgen action. Trends Endocrinol. Metab. 9 (8): 317–24.
- ↑ McPhaul MJ, Young M (September 2001). Complexities of androgen action. J. Am. Acad. Dermatol. 45 (3 Suppl): S87–94.
- ↑ Breiner M, Romalo G, Schweikert HU (August 1986). Inhibition of androgen receptor binding by natural and synthetic steroids in cultured human genital skin fibroblasts. Klin. Wochenschr. 64 (16): 732–7.
References
- Ajayi AAL, Mathur R, Halushka PV. Testosterone increases platelet TXA2 receptor density and aggregation responses (1995). Circulation 91 : 2742-7.
- Ajayi AAL, Halushka PV. Castration reduces platelet TXA2 receptor density and aggregability (2005). QJM 98 : 349-57.
- Bhasin S, Storer TW, Berman N, et al (1996). The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N. Engl. J. Med. 335 (1): 1–7.
- E.R. Freeman, D.A. Bloom, and E.J. McGuire (2001). A brief history of testosterone. Journal of Urology 165: 371–373.
- J.M. Hoberman and C.E. Yesalis (1995). The history of synthetic testosterone. Scientific American 272: 76–81.
- P.R. Larsen et al. (2003). Williams textbook of endocrinology, 10th, Saunders. (Seventh edition by J.D. Wilson and R.H. Williams, 1985, ISBN 072161082X.)
- S.D. Moffat and E. Hampson (1996). A curvilinear relationship between testosterone and spatial cognition in humans: Possible influence of hand preference. Psychoneuroendocrinology 21 (3): 323–337.
- S.D. Moffat, A.B. Zonderman, E.J. Metter et al. (2004). Free testosterone and risk for Alzheimer's disease in older men. Neurology 62: 188–193.
- M. Parssinen, U. Kujala, E. Vartiainen, et al. (2000). Increased premature mortality of competitive powerlifters suspected to have used anabolic agents. International Journal of Sports Medicine 21: 225–227.
- C.J. Pike, E.R. Rosario, and T.V. Nguyen (2006). Androgens, aging, and Alzheimer's disease. Endocrine 29 (2): 233–241.
- E.R. Rosario, L. Chang, F.K. Stanczyk, et al. (2004). Age-Related Testosterone Depletion and the Development of Alzheimer Disease. JAMA 292 (12): 1431–1432.
- M. Solms and O. Turnbull (2002). The brain and the inner world, Other Press, New York.
- World Health Organization Task Force on methods for the regulation of male fertility (1990). Contraceptive efficacy of testosterone-induced azoospermia in normal men. Lancet 336: 955–959.
External links
- NIST entry for Testosterone
- NIST results of search for Testosterone (Shows androstenone.)
- Results of research on the efficacy of differing body locations for the absorption of topical testosterone creams
- A general pdf booklet that discusses the history, uses in Men, various treatments available, etc.
- "Calls for testosterone trials in CHD "
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Target-derived NGF, BDNF, NT-3
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Sex hormones and related agents (primarily G03, also L02, H01C) - human endogenous in CAPS
| |
|---|---|
| Progestogens: (receptor) |
PROGESTERONE, Desogestrel, Drospirenone, Dydrogesterone, Ethisterone, Etonogestrel, Ethynodiol diacetate, Gestodene, Gestonorone, Levonorgestrel, Lynestrenol, Medroxyprogesterone, Megestrol, Norelgestromin,
Norethisterone, Norethynodrel, Norgestimate, Norgestrel, Norgestrienone, Tibolone |
| Androgens: (receptor) |
TESTOSTERONE, Androstanolone, Fluoxymesterone, Mesterolone, Methyltestosterone, (see also anabolic steroids) Antiandrogens: Bicalutamide, Cyproterone, Flutamide, Nilutamide, Spironolactone |
| Estrogens: (receptor) |
ESTRADIOL, ESTRIOL, ESTRONE, Chlorotrianisene, Dienestrol, Diethylstilbestrol, Ethinylestradiol, Fosfestrol, Mestranol, Polyestradiol phosphate Selective estrogen receptor modulator: Bazedoxifene, Clomifene, Fulvestrant, Raloxifene, Tamoxifen, Toremifene Aromatase inhibitor: Aminogluthetimide, Anastrozole, Exemestane, Formestane, Letrozole, Vorozole |
| Gonadotropins: (FSHR/LHCGR) |
ovulation stim.: Clomifene, Urofollitropin Antigonadotropins: Danazol, Gestrinone |
| GnRH: (receptor) |
agonist: Buserelin, Goserelin, Histrelin, Leuprorelin, Nafarelin, Triptorelin antagonist: Abarelix, Cetrorelix, Ganirelix |
Anabolic steroids (A14) (trademark names in brackets) | |
|---|---|
| Androstan (carbon 19 present) |
Androstadienone • Boldenone undecylenate (Equipoise) • Desoxymethyltestosterone (Madol) • DHT • Methandrostenolone (Dianabol) • Methenolone • Norethandrolone • Oxandrolone (Anavar) • Oxymetholone (Anadrol) • Quinbolone (Anabolicum Vister) • Stanozolol (Winstrol) • Testosterone • Clostebol • 4-Chlordehydromethyltestosterone (Turinabol) • Fluoxymesterone (Halotestin) • Drostanolone (Masteron) • DHEA • Oxymetholone (Anadrol-50) • Mesterolone (Proviron) • Methenolone enanthate (Primobolan) • Mestanolone |
| Estren (carbon 19 absent) |
Ethylestrenol • Nandrolone (Deca Durabolin) • Norbolethone (Genabol) • Oxabolone cipionate • Trenbolone (Fina) • Mibolerone (Cheque Drops) • Tetrahydrogestrinone (The Clear) |
Template:Cholesterol and steroid intermediates
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