Editing Androgen (section)

==Biological function==

===Male prenatal development===

====Testes formation====
During mammalian development, the gonads are at first capable of becoming either [[ovary|ovaries]] or testes.<ref>{{Cite book  |year=2000 |title=Developmental Biology |publisher=[[Sinauer Associates]] |location=[[Sunderland, Massachusetts]] |edition=6th |isbn=978-0-87893-243-6 |url=https://archive.org/details/developmentalbio00gilb | vauthors = Gilbert SF |url-access=registration }}{{Page needed|date=September 2010}}</ref> In humans, starting at about week 4, the gonadal rudiments are present within the [[intermediate mesoderm]] adjacent to the developing kidneys. At about week 6, epithelial [[sex cords]] develop within the forming testes and incorporate the [[germ cell]]s as they migrate into the gonads. In males, certain [[Y chromosome]] genes, particularly [[SRY]], control development of the male phenotype, including conversion of the early bipotential gonad into testes. In males, the sex cords fully invade the developing gonads.

====Androgen production====
The mesoderm-derived [[Epithelium|epithelial]] cells of the sex cords in developing testes become the [[Sertoli cell]]s, which will function to support sperm cell formation. A minor population of nonepithelial cells appear between the tubules by week 8 of human fetal development. These are [[Leydig cell]]s. Soon after they differentiate, Leydig cells begin to produce androgens.

====Androgen effects====
The androgens function as [[Paracrine signalling|paracrine]] [[hormone]]s required by the Sertoli cells to support sperm production. They are also required for the masculinization of the developing male fetus (including penis and scrotum formation). Under the influence of androgens, remnants of the [[mesonephron]], the [[Wolffian ducts]], develop into the [[epididymis]], [[vas deferens]] and [[seminal vesicles]]. This action of androgens is supported by a hormone from Sertoli cells, Müllerian inhibitory hormone (MIH), which prevents the embryonic Müllerian ducts from developing into fallopian tubes and other female reproductive tract tissues in male embryos. MIH and androgens cooperate to allow for movement of testes into the scrotum.

====Early regulation====
Before the production of the pituitary hormone [[luteinizing hormone]] (LH) by the embryo starting at about weeks 11–12, [[human chorionic gonadotrophin]] (hCG) promotes the differentiation of Leydig cells and their production of androgens at week 8.  Androgen action in target tissues often involves conversion of testosterone to 5α-[[dihydrotestosterone]] (DHT).

===Male pubertal development===
At the time of [[puberty]], androgen levels increase dramatically in males, and androgens mediate the development of masculine [[secondary sexual characteristic]]s as well as the activation of [[spermatogenesis]] and [[fertility]] and masculine behavioral changes such as increased [[sex drive]]. Masculine secondary sexual characteristics include [[androgenic hair]], [[voice deepening]], emergence of the [[Adam's apple]], broadening of the shoulders, increased [[muscle mass]], and [[penile growth]].

===Spermatogenesis===
During puberty, androgen, LH and [[follicle stimulating hormone]] (FSH) production increase and the sex cords hollow out, forming the seminiferous tubules, and the germ cells start to differentiate into sperm. Throughout adulthood, androgens and FSH cooperatively act on Sertoli cells in the testes to support sperm production.<ref>{{Cite book|editor1=Saffron A. Whitehead |editor2=Stephen Nussey |title=Endocrinology: an integrated approach |publisher=[[British Institute of Organ Studies]] |location=Oxford |year=2001 |isbn=978-1-85996-252-7 |url=https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=endocrin |author1=Stephen Nussey |author2=Saffron Whitehead }}{{Page needed|date=September 2010}}</ref> Exogenous androgen supplements can be used as a [[male contraceptive]]. Elevated androgen levels caused by use of androgen supplements can inhibit production of LH and block production of endogenous androgens by Leydig cells. Without the locally high levels of androgens in testes due to androgen production by Leydig cells, the seminiferous tubules can degenerate, resulting in infertility. For this reason, many transdermal androgen patches are applied to the scrotum.

===Fat deposition===
Males typically have less body fat than females. Recent results indicate androgens inhibit the ability of some fat cells to store lipids by blocking a signal transduction pathway that normally supports adipocyte function.<ref name="Singh R, Artaza JN, Taylor WE, et al. 2006 141–54">{{cite journal | vauthors = Singh R, Artaza JN, Taylor WE, Braga M, Yuan X, Gonzalez-Cadavid NF, Bhasin S | title = Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors | journal = Endocrinology | volume = 147 | issue = 1 | pages = 141–154 | date = January 2006 | pmid = 16210377 | pmc = 4417624 | doi = 10.1210/en.2004-1649 }}</ref> Also, androgens, but not estrogens, increase beta [[adrenergic receptor]]s while decreasing alpha adrenergic receptors—which results in increased levels of epinephrine/norepinephrine due to lack of alpha-2 receptor negative feedback and decreased fat accumulation due to epinephrine/norepinephrine then acting on lipolysis-inducing beta receptors.

===Muscle mass===
Males typically have more [[skeletal muscle]] mass than females. Androgens promote the enlargement of skeletal muscle cells in a coordinated manner by acting on several cell types in skeletal muscle tissue.<ref>{{cite journal | vauthors = Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S | title = Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 89 | issue = 10 | pages = 5245–5255 | date = October 2004 | pmid = 15472231 | doi = 10.1210/jc.2004-0084 | doi-access = free }}</ref> One cell type, called the [[Muscle cell|myoblast]], conveys androgen receptors for generating muscle. Fusion of myoblasts generates [[myotube]]s, in a process linked to androgen receptor levels.<ref name="pmid15623502">{{cite journal | vauthors = Vlahopoulos S, Zimmer WE, Jenster G, Belaguli NS, Balk SP, Brinkmann AO, Lanz RB, Zoumpourlis VC, Schwartz RJ | display-authors = 6 | title = Recruitment of the androgen receptor via serum response factor facilitates expression of a myogenic gene | journal = The Journal of Biological Chemistry | volume = 280 | issue = 9 | pages = 7786–7792 | date = March 2005 | pmid = 15623502 | doi = 10.1074/jbc.M413992200 | doi-access = free }}</ref> Higher androgen levels lead to increased expression of [[androgen receptor]].

===Brain===
Circulating levels of androgens can influence human behavior because some [[neuron]]s are sensitive to steroid hormones. Androgen levels have been implicated in the regulation of human [[aggression]] and libido. Indeed, androgens are capable of altering the structure of the brain in several species, including mice, rats, and primates, producing [[sex differences]].<ref>{{cite journal | vauthors = Cooke B, Hegstrom CD, Villeneuve LS, Breedlove SM | title = Sexual differentiation of the vertebrate brain: principles and mechanisms | journal = Frontiers in Neuroendocrinology | volume = 19 | issue = 4 | pages = 323–362 | date = October 1998 | pmid = 9799588 | doi = 10.1006/frne.1998.0171 | s2cid = 14372914 }}</ref> More recent studies showing the general [[Mood (psychology)|mood]] of [[transgender men]], who have undergone [[transgender hormone replacement therapy]] replacing [[estrogen]]s with androgens, do not show any substantial long-term [[behavioral]] changes.<ref>{{cite journal | vauthors = Irwig MS | title = Testosterone therapy for transgender men | journal = The Lancet. Diabetes & Endocrinology | volume = 5 | issue = 4 | pages = 301–311 | date = April 2017 | pmid = 27084565 | doi = 10.1016/S2213-8587(16)00036-X }}</ref><ref>{{cite journal | vauthors = Costantino A, Cerpolini S, Alvisi S, Morselli PG, Venturoli S, Meriggiola MC | title = A prospective study on sexual function and mood in female-to-male transsexuals during testosterone administration and after sex reassignment surgery | journal = Journal of Sex & Marital Therapy | volume = 39 | issue = 4 | pages = 321–335 | date = 14 February 2013 | pmid = 23470169 | doi = 10.1080/0092623X.2012.736920 | s2cid = 34943756 }}</ref><ref>{{cite journal | vauthors = Johnson JM, Nachtigall LB, Stern TA | title = The effect of testosterone levels on mood in men: a review | journal = Psychosomatics | volume = 54 | issue = 6 | pages = 509–514 | date = 1 November 2013 | pmid = 24016385 | doi = 10.1016/j.psym.2013.06.018 }}</ref>

Numerous reports have shown androgens alone are capable of altering the [[structure of the brain]],<ref>{{cite journal | vauthors = Zuloaga DG, Puts DA, Jordan CL, Breedlove SM | title = The role of androgen receptors in the masculinization of brain and behavior: what we've learned from the testicular feminization mutation | journal = Hormones and Behavior | volume = 53 | issue = 5 | pages = 613–626 | date = May 2008 | pmid = 18374335 | pmc = 2706155 | doi = 10.1016/j.yhbeh.2008.01.013 }}</ref> but identification of which alterations in neuroanatomy stem from androgens or estrogens is difficult, because of their potential for conversion.

Evidence from [[neurogenesis]] (formation of new neurons) studies on male rats has shown that the [[hippocampus]] is a useful brain region to examine when determining the effects of androgens on behavior. To examine [[neurogenesis]], wild-type male rats were compared with male rats that had [[androgen insensitivity syndrome]], a genetic difference resulting in complete or partial insensitivity to androgens and a lack of external [[male genitalia]].

Neural injections of [[bromodeoxyuridine]] (BrdU) were applied to males of both groups to test for [[neurogenesis]]. Analysis showed that [[testosterone]] and [[dihydrotestosterone]] regulated adult [[Hippocampal formation|hippocampal]] [[neurogenesis]] (AHN). Adult hippocampal neurogenesis was regulated through the [[androgen receptor]] in the wild-type male rats, but not in the TMF male rats. To further test the role of activated androgen receptors on AHN, [[flutamide]], an [[antiandrogen]] drug that competes with testosterone and dihydrotestosterone for androgen receptors, and dihydrotestosterone were administered to normal male rats. Dihydrotestosterone increased the number of BrdU cells, while flutamide inhibited these cells. Moreover, estrogens had no effect. This research demonstrates how androgens can increase AHN.<ref name="pmid23782943">{{cite journal | vauthors = Hamson DK, Wainwright SR, Taylor JR, Jones BA, Watson NV, Galea LA | title = Androgens increase survival of adult-born neurons in the dentate gyrus by an androgen receptor-dependent mechanism in male rats | journal = Endocrinology | volume = 154 | issue = 9 | pages = 3294–3304 | date = September 2013 | pmid = 23782943 | doi = 10.1210/en.2013-1129 | hdl-access = free | doi-access = free | hdl = 2429/63213 }}</ref>

Researchers also examined how mild exercise affected androgen synthesis which in turn causes AHN activation of [[N-Methyl-D-aspartic acid|''N''-methyl-{{sc|D}}-aspartate (NMDA)]] receptors. [[NMDA]] induces a calcium flux that allows for synaptic plasticity which is crucial for AHN.

Researchers injected both orchidectomized (ORX) (castrated) and sham castrated male rats with [[BrdU]] to determine if the number of new cells was increased. They found that AHN in male rats is increased with mild exercise by boosting synthesis of [[dihydrotestosterone]] in the [[hippocampus]]. Again it was noted that AHN was not increased via activation of the [[estrogen receptor]]s.<ref>{{cite journal | vauthors = Okamoto M, Hojo Y, Inoue K, Matsui T, Kawato S, McEwen BS, Soya H | title = Mild exercise increases dihydrotestosterone in hippocampus providing evidence for androgenic mediation of neurogenesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 32 | pages = 13100–13105 | date = August 2012 | pmid = 22807478 | pmc = 3420174 | doi = 10.1073/pnas.1210023109 | doi-access = free | bibcode = 2012PNAS..10913100O }}</ref>

Androgen regulation decreases the likelihood of [[Depression (clinical)|depression]] in males. In [[preadolescent]] male rats, [[neonatal]] rats treated with [[flutamide]] developed more [[Depression symptoms|depression-like symptoms]] compared to control rats.

Again [[BrdU]] was injected into both groups of rats in order to see if cells were multiplying in the living tissue. These results demonstrate how the organization of androgens has a positive effect on [[preadolescent]] [[Hippocampal formation|hippocampal]] [[neurogenesis]] that may be linked with lower [[Depression symptoms|depression-like symptoms]].<ref name="pmid20399256">{{cite journal | vauthors = Zhang JM, Tonelli L, Regenold WT, McCarthy MM | title = Effects of neonatal flutamide treatment on hippocampal neurogenesis and synaptogenesis correlate with depression-like behaviors in preadolescent male rats | journal = Neuroscience | volume = 169 | issue = 1 | pages = 544–554 | date = August 2010 | pmid = 20399256 | pmc = 3574794 | doi = 10.1016/j.neuroscience.2010.03.029 }}</ref>

[[Social isolation]] has a hindering effect in AHN whereas normal regulation of androgens increases AHN. A study using male rats showed that [[testosterone]] may block [[social isolation]], which results in [[Hippocampal formation|hippocampal]] [[neurogenesis]] reaching [[homeostasis]]—regulation that keeps internal conditions stable. A [[BrdU|Brdu]] analysis showed that excess [[testosterone]] did not increase this blocking effect against [[social isolation]]; that is, the natural circulating levels of androgens cancel out the negative effects of [[social isolation]] on AHN.<ref name="pmid21875652">{{cite journal | vauthors = Spritzer MD, Ibler E, Inglis W, Curtis MG | title = Testosterone and social isolation influence adult neurogenesis in the dentate gyrus of male rats | journal = Neuroscience | volume = 195 | pages = 180–190 | date = November 2011 | pmid = 21875652 | pmc = 3198792 | doi = 10.1016/j.neuroscience.2011.08.034 }}</ref>

===Female-specific effects===
Androgens have potential roles in relaxation of the [[myometrium]] via non-genomic, [[androgen receptor]]-independent pathways, preventing premature [[uterine contraction]]s in pregnancy.<ref name="MakievaSaunders2014">{{cite journal | vauthors = Makieva S, Saunders PT, Norman JE | title = Androgens in pregnancy: roles in parturition | journal = Human Reproduction Update | volume = 20 | issue = 4 | pages = 542–559 | year = 2014 | pmid = 24643344 | pmc = 4063701 | doi = 10.1093/humupd/dmu008 }}</ref>

===Androgen insensitivity===
{{Main|Androgen insensitivity syndrome}}
Reduced ability of an [[sex chromosome|XY]]-[[karyotype]] fetus to respond to androgens can result in one of several conditions, including infertility and several forms of [[intersex]] conditions.

===Miscellaneous===
Yolk androgen levels in certain birds have been positively correlated to social dominance later in life. See [[American coot]].