Editing Testosterone (section)

===Steroid hormone activity===
The effects of testosterone in humans and other [[vertebrates]] occur by way of multiple mechanisms: by activation of the [[androgen receptor]] (directly or as dihydrotestosterone), and by conversion to [[estradiol]] and activation of certain [[estrogen receptor]]s.<ref name="pmid18406296">{{cite journal | vauthors = Hiipakka RA, Liao S | s2cid = 23385663 | title = Molecular mechanism of androgen action | journal = Trends in Endocrinology and Metabolism | volume = 9 | issue = 8 | pages = 317–24 | date = Oct 1998 | pmid = 18406296 | doi = 10.1016/S1043-2760(98)00081-2 }}</ref><ref name="pmid11511858">{{cite journal | vauthors = McPhaul MJ, Young M | title = Complexities of androgen action | journal = Journal of the American Academy of Dermatology | volume = 45 | issue = 3 Suppl | pages = S87–94 | date = Sep 2001 | pmid = 11511858 | doi = 10.1067/mjd.2001.117429 }}</ref> Androgens such as testosterone have also been found to bind to and activate [[membrane androgen receptor]]s.<ref name="pmid19931639">{{cite journal | vauthors = Bennett NC, Gardiner RA, Hooper JD, Johnson DW, Gobe GC | title = Molecular cell biology of androgen receptor signalling | journal = Int. J. Biochem. Cell Biol. | volume = 42 | issue = 6 | pages = 813–27 | year = 2010 | pmid = 19931639 | doi = 10.1016/j.biocel.2009.11.013 }}</ref><ref name="pmid25257522">{{cite journal | vauthors = Wang C, Liu Y, Cao JM | title = G protein-coupled receptors: extranuclear mediators for the non-genomic actions of steroids | journal = Int J Mol Sci | volume = 15 | issue = 9 | pages = 15412–25 | year = 2014 | pmid = 25257522 | pmc = 4200746 | doi = 10.3390/ijms150915412 | doi-access = free }}</ref><ref name="pmid23746222">{{cite journal | vauthors = Lang F, Alevizopoulos K, Stournaras C | s2cid = 23918273 | title = Targeting membrane androgen receptors in tumors | journal = Expert Opin. Ther. Targets | volume = 17 | issue = 8 | pages = 951–63 | year = 2013 | pmid = 23746222 | doi = 10.1517/14728222.2013.806491 }}</ref>

[[#Free testosterone|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 [[Dihydrotestosterone|5α-dihydrotestosterone]] (5α-DHT) by the cytoplasmic enzyme [[5α-reductase]]. 5α-DHT binds to the same androgen receptor even more strongly than testosterone, so that its androgenic potency is about 5 times that of T.<ref name="pmid3762019">{{cite journal | vauthors = Breiner M, Romalo G, Schweikert HU | s2cid = 34846760 | title = Inhibition of androgen receptor binding by natural and synthetic steroids in cultured human genital skin fibroblasts | journal = Klinische Wochenschrift | volume = 64 | issue = 16 | pages = 732–37 | date = August 1986 | pmid = 3762019 | doi = 10.1007/BF01734339 }}</ref> The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the [[cell nucleus]] and bind directly to specific [[nucleotide]] sequences of the [[chromosome|chromosomal]] DNA. The areas of binding are called [[hormone response element]]s (HREs), and influence transcriptional activity of certain [[gene]]s, producing the androgen effects.

Androgen receptors occur in many different vertebrate body system tissues, and both males and females respond similarly to similar levels. Greatly differing amounts of testosterone prenatally, at puberty, and throughout life account for a share of [[sexual differentiation|biological differences]] between males and females.

The bones and the brain are two important tissues in humans where the primary effect of testosterone is by way of [[aromatization]] to [[estradiol]]. In the bones, estradiol accelerates ossification of cartilage into bone, leading to closure of the [[epiphysis|epiphyses]] and conclusion of growth. In the central nervous system, testosterone is aromatized to estradiol. Estradiol rather than testosterone serves as the most important feedback signal to the hypothalamus (especially affecting [[luteinizing hormone|LH]] secretion).<ref>{{cite book | vauthors = Kelly MJ, Qiu J, Rønnekleiv OK | title = Estrogen signaling in the hypothalamus | volume = 71 | pages = 123–45 | date = 2005-01-01 | pmid = 16112267 | doi = 10.1016/S0083-6729(05)71005-0 | series = Vitamins & Hormones | publisher = Academic Press | isbn = 978-0-12-709871-5 }}</ref>{{Failed verification|date=February 2023}} In many [[mammal]]s, prenatal or perinatal "masculinization" of the [[sexual dimorphism|sexually dimorphic]] areas of the brain by estradiol derived from testosterone programs later male sexual behavior.<ref name="pmid18195084">{{cite journal | vauthors = McCarthy MM | title = Estradiol and the developing brain | journal = Physiological Reviews | volume = 88 | issue = 1 | pages = 91–124 | year = 2008 | pmid = 18195084 | pmc = 2754262 | doi = 10.1152/physrev.00010.2007 }}</ref>