Editing Androsterone

{{Short description|Endogenous steroid hormone}}
{{Distinguish|Androstenone|Androstenedione|Androstadienol}}
{{Use mdy dates|date=December 2023}}{{cs1 config|name-list-style=vanc}}{{Use PMID reference names|date=December 2023}}
{{Infobox drug
| verifiedrevid = 457130388
| IUPAC_name = (3''R'',5''S'',8''R'',9''S'',10''S'',13''S'',14''S'')-3-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[''a'']phenanthren-17-one
| image = androsteron.svg
| image_class = skin-invert-image
| alt = Skeletal formula of androsterone
| width = 210
| image2 = Androsterone-3D-balls.png
| alt2 = Ball-and-stick model of the androsterone molecule
| width2 = 220
<!--Clinical data-->
| pregnancy_category =
| legal_status =
| routes_of_administration =
<!--Pharmacokinetic data-->
| bioavailability =
| metabolism =
| excretion =
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 53-41-8
| ATC_prefix = none
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 87285
| PubChem = 5879
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5668
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = C24W7J5D5R
| synonyms = 3α-hydroxy-5α-androstan-17-one, 5α-androstan-3α-ol-17-one
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 16032
<!--Chemical data-->
| C=19 | H=30
| O=2
| smiles = O=C2[C@]1(CC[C@H]3[C@H]([C@@H]1CC2)CC[C@H]4C[C@H](O)CC[C@]34C)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C19H30O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h12-16,20H,3-11H2,1-2H3/t12-,13+,14-,15-,16-,18-,19-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = QGXBDMJGAMFCBF-HLUDHZFRSA-N
}}
'''Androsterone''', or '''3α-hydroxy-5α-androstan-17-one''', is an [[endogenous]] [[steroid hormone]], [[neurosteroid]], and putative [[pheromone]].<ref name="pmid21489118">{{cite journal | vauthors = Motofei IG | title = A dual physiological character for cerebral mechanisms of sexuality and cognition: common somatic peripheral afferents | journal = BJU International | volume = 108 | issue = 10 | pages = 1634–1639 | date = November 2011 | pmid = 21489118 | doi = 10.1111/j.1464-410X.2011.10116.x | s2cid = 25941894 }}</ref> It is a weak [[androgen]] with a [[potency (pharmacology)|potency]] that is approximately 1/7 that of [[testosterone]].<ref name="Scott1996">{{cite book | vauthors = Scott T | title = Concise Encyclopedia Biology | url = https://books.google.com/books?id=LorrYj5pkKYC&pg=PA49 | access-date = May 25, 2012 | year = 1996 | publisher = Walter de Gruyter | isbn = 978-3-11-010661-9 | page = 49 | archive-date = March 8, 2024 | archive-url = https://web.archive.org/web/20240308025011/https://books.google.com/books?id=LorrYj5pkKYC&pg=PA49 | url-status = live }}</ref> Androsterone is a [[metabolite]] of testosterone and [[dihydrotestosterone]] (DHT). In addition, it can be converted back into DHT via [[3α-hydroxysteroid dehydrogenase]] and [[17β-hydroxysteroid dehydrogenase]], bypassing conventional intermediates such as [[androstanedione]] and testosterone, and as such, can be considered to be a [[metabolic intermediate]] in its own right.<ref name="HendersonPonder2003">{{cite book | vauthors = Stanczyk FZ, Bretsky | chapter = Biosynthesis, Transport, and Metabolism of Steroid HormonesHenderson BE, Ponder BA, Ross RK | title = Hormones, Genes, and Cancer | chapter-url = https://books.google.com/books?id=VzIWd4faVVQC&pg=PA23 | access-date = May 25, 2012 | date = March 13, 2003 | publisher = Oxford University Press | isbn = 978-0-19-513576-3 | page = 23 }}</ref><ref name="pmid22170725">{{cite journal | vauthors = Kamrath C, Hochberg Z, Hartmann MF, Remer T, Wudy SA | title = Increased activation of the alternative "backdoor" pathway in patients with 21-hydroxylase deficiency: evidence from urinary steroid hormone analysis | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 97 | issue = 3 | pages = E367–E375 | date = March 2012 | pmid = 22170725 | doi = 10.1210/jc.2011-1997 | doi-access = free }}</ref>

Androsterone is also known to be an [[inhibitory postsynaptic potential|inhibitory]] [[androstane]] [[neurosteroid]],<ref name="pmid22787590">{{cite book | vauthors = Reddy DS, Rogawski MA | chapter = Neurosteroids — Endogenous Regulators of Seizure Susceptibility and Role in the Treatment of Epilepsy | veditors = Noebels JL, Avoli M, Rogawski MA | title = Jasper's Basic Mechanisms of the Epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US) | date = 2012 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK98218/ | display-editors = etal | publisher = National Center for Biotechnology Information (US) | pmid = 22787590 | access-date = August 29, 2017 | archive-date = September 25, 2019 | archive-url = https://web.archive.org/web/20190925133626/https://www.ncbi.nlm.nih.gov/books/NBK98218/ | url-status = live }}</ref><ref name="pmid21094889">{{cite book | vauthors = Reddy DS | chapter = Neurosteroids | title = Sex Differences in the Human Brain, their Underpinnings and Implications | volume = 186 | pages = 113–137 | year = 2010 | pmid = 21094889 | pmc = 3139029 | doi = 10.1016/B978-0-444-53630-3.00008-7 | isbn = 9780444536303 | series = Progress in Brain Research }}</ref> acting as a [[positive allosteric modulator]] of the [[GABAA receptor|GABA<sub>A</sub> receptor]],<ref name="pmid17341652">{{cite journal | vauthors = Li P, Bracamontes J, Katona BW, Covey DF, Steinbach JH, Akk G | title = Natural and enantiomeric etiocholanolone interact with distinct sites on the rat alpha1beta2gamma2L GABAA receptor | journal = Molecular Pharmacology | volume = 71 | issue = 6 | pages = 1582–1590 | date = June 2007 | pmid = 17341652 | pmc = 3788649 | doi = 10.1124/mol.106.033407 | s2cid = 44286086 }}</ref> and possesses [[anticonvulsant]] effects.<ref name="pmid15946323">{{cite journal | vauthors = Kaminski RM, Marini H, Kim WJ, Rogawski MA | title = Anticonvulsant activity of androsterone and etiocholanolone | journal = Epilepsia | volume = 46 | issue = 6 | pages = 819–827 | date = June 2005 | pmid = 15946323 | pmc = 1181535 | doi = 10.1111/j.1528-1167.2005.00705.x }}</ref> The unnatural enantiomer of androsterone is more potent as a positive allosteric modulator of GABA<sub>A</sub> receptors and as an anticonvulsant than the natural form.<ref name="pmid24705905">{{cite journal | vauthors = Zolkowska D, Dhir A, Krishnan K, Covey DF, Rogawski MA | title = Anticonvulsant potencies of the enantiomers of the neurosteroids androsterone and etiocholanolone exceed those of the natural forms | journal = Psychopharmacology | volume = 231 | issue = 17 | pages = 3325–3332 | date = September 2014 | pmid = 24705905 | pmc = 4134984 | doi = 10.1007/s00213-014-3546-x }}</ref> Androsterone's 3β-[[isomer]] is [[epiandrosterone]], and its 5β-[[epimer]] is [[etiocholanolone]]. The 3β,5β-isomer is [[epietiocholanolone]].

==Biological function==
Androsterone has generally been considered to be an inactive metabolite of testosterone, which when conjugated by glucuronidation and sulfation allows testosterone to be removed from the body, but it is a weak [[neurosteroid]] that can cross into the brain and could have effects on brain function.<ref name="pmid15946323" />

The view of androsterone as generally being of low significance however, seems to need review in the light of 21st century research, which suggests that androsterone significantly affects [[Virilization|masculinization]] in mammalian fetuses. Masculinization of the external genitalia in humans is subject to dihydrotestosterone (DHT) derived via the recognised androgenic pathway and also via a [[androgen backdoor pathway|backdoor pathway]].<ref name=wj>{{cite journal|doi=10.15347/WJM/2023.003  |doi-access=free |title=Alternative androgen pathways |year=2023 | vauthors = Masiutin M, Yadav M |journal=WikiJournal of Medicine |volume=10 |pages=X |s2cid=257943362}}</ref> Therefore, androstanediol can be used a marker of the backdoor pathway of DHT synthesis.<ref name="pmid32871622">{{cite journal | vauthors = Rohayem J, Zitzmann M, Laurentino S, Kliesch S, Nieschlag E, Holterhus PM, Kulle A | title = The role of gonadotropins in testicular and adrenal androgen biosynthesis pathways-Insights from males with congenital hypogonadotropic hypogonadism on hCG/rFSH and on testosterone replacement | journal = Clinical Endocrinology | volume = 94 | issue = 1 | pages = 90–101 | date = January 2021 | pmid = 32871622 | doi = 10.1111/cen.14324 | doi-access = free }}</ref> Spectrometric studies identify androsterone as the main backdoor androgen in the human male fetus. Circulating levels are sex dependent, DHT being essentially absent in the female, in which titres of backdoor intermediates also are very low.<ref name="pmid30763313"/>

In males, backdoor intermediates occur mainly in the liver and adrenal of the fetus, and in the placenta — hardly at all in the testis. Instead, progesterone in the placenta is the main backdoor substrate for androgen synthesis. This also is consistent with the observation that placental insufficiency has been associated with disruptions of development of fetal genitalia.<ref name="pmid30763313">{{cite journal | vauthors = O'Shaughnessy PJ, Antignac JP, Le Bizec B, Morvan ML, Svechnikov K, Söder O, Savchuk I, Monteiro A, Soffientini U, Johnston ZC, Bellingham M, Hough D, Walker N, Filis P, Fowler PA | display-authors = 6 | title = Alternative (backdoor) androgen production and masculinization in the human fetus | journal = PLOS Biology | volume = 17 | issue = 2 | pages = e3000002 | date = February 2019 | pmid = 30763313 | pmc = 6375548 | doi = 10.1371/journal.pbio.3000002 | doi-access = free }}</ref>

===Pheromone===
Androsterone is found in the human [[axilla]] and [[skin]] as well as in the [[urine]].<ref name="MaiwormLangthaler1992">{{cite book| vauthors = Maiworm RE, Langthaler WU |chapter=Influence of Androstenol and Androsterone on the Evalulation of Men of Varying Attractiveness Levels |title=Chemical Signals in Vertebrates 6 |year=1992|pages=575–579|doi=10.1007/978-1-4757-9655-1_88|isbn=978-1-4757-9657-5}}</ref> It may also be secreted by human [[sebaceous gland]]s.<ref name="MaiwormLangthaler1992" /> It is described as having a musky odor similar to that of [[androstenol]].<ref name="MaiwormLangthaler1992" /> Androsterone has been found to affect human behavior when smelled.<ref name="MaiwormLangthaler1992" />

==Biochemistry==

===Biosynthesis===
Androsterone and its 5β-isomer, [[etiocholanolone]], are produced in the body as metabolites of [[testosterone]]. Testosterone is converted to 5α-dihydrotestosterone and [[5β-dihydrotestosterone]] by [[5α-reductase]] and [[5β-reductase]], respectively. The enzyme [[3α-hydroxysteroid dehydrogenase]] converts the reduced forms to [[3α-androstanediol]] and [[androstanediol|3β-androstanediol]], which are subsequently converted by [[17β-hydroxysteroid dehydrogenase]] to androsterone and etiocholanolone, respectively. Androsterone and etiocholanolone can also be formed from [[androstenedione]] via the action of 5α-reductase and 5β-reductase forming [[5α-androstanedione]] and [[5β-androstanedione]] which are then converted to androsterone and etiocholanolone by [[3α-hydroxysteroid dehydrogenase]] and [[3β-hydroxysteroid dehydrogenase]], respectively.<ref name="pmid15946323" />

===Metabolism===
Androsterone is [[sulfation|sulfated]] into [[androsterone sulfate]] and [[glucuronidation|glucuronidated]] into [[androsterone glucuronide]] and these [[conjugation (biochemistry)|conjugate]]s are [[excretion|excreted]] in [[urine]].

==Chemistry==
{{See also|List of neurosteroids}}

===Sources===
Androsterone has been shown to naturally occur in [[pine]] [[pollen]], celery, [[truffle]]s and is well known in many [[animal]] [[species]].<ref name="pmid16044944">{{cite journal | vauthors = Janeczko A, Skoczowski A | title = Mammalian sex hormones in plants | journal = Folia Histochemica et Cytobiologica | volume = 43 | issue = 2 | pages = 71–79 | date = 2005 | pmid = 16044944 }}</ref><ref name="pmid2813372">{{cite journal | vauthors = Wysocki CJ, Dorries KM, Beauchamp GK | title = Ability to perceive androstenone can be acquired by ostensibly anosmic people | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 20 | pages = 7976–7978 | date = October 1989 | pmid = 2813372 | pmc = 298195 | doi = 10.1073/pnas.86.20.7976 | doi-access = free | bibcode = 1989PNAS...86.7976W }}</ref>

==History==
Androsterone was first isolated in 1931, by [[Adolf Friedrich Johann Butenandt]] and [[Kurt Tscherning]]. They distilled over {{convert|17000|liter}} of male urine, from which they got {{convert|50|mg}} of crystalline androsterone, which was sufficient to find that the chemical formula was very similar to [[estrone]].

== See also ==
* [[Androgen backdoor pathway]]
* [[List of androgens/anabolic steroids]]
* [[List of neurosteroids#Androstanes|List of neurosteroids § Androstanes]]
* [[List of neurosteroids#Pheromones and pherines|List of neurosteroids § Pheromones and pherines]]
* [[3α-Hydroxysteroid dehydrogenase]]

== References ==
{{Reflist}}

== External links ==
* [https://web.archive.org/web/20080117071259/http://www.hmdb.ca/scripts/show_card.cgi?METABOCARD=HMDB00031 Androsterone entry in the HMDB]

{{Pheromones and pherines}}
{{Endogenous steroids}}
{{Androgen receptor modulators}}
{{GABAA receptor positive modulators}}

[[Category:5α-Reduced steroid metabolites]]
[[Category:Anabolic–androgenic steroids]]
[[Category:Androstanes]]
[[Category:Hormones of the liver]]
[[Category:Human metabolites]]
[[Category:Human pheromones]]
[[Category:Mammalian pheromones]]
[[Category:Neurosteroids]]
[[Category:Steroid hormones]]
[[Category:GABAA receptor positive allosteric modulators]]