Androsterone

Androsterone
Systematic (IUPAC) name
(3R,5S,8R,9S,10S,13S,14S)-3-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-one
Clinical data
Identifiers
53-41-8 Yes
None
PubChem CID 5879
ChemSpider 5668 Yes
UNII C24W7J5D5R Yes
ChEBI CHEBI:16032 Yes
ChEMBL CHEMBL87285 Yes
Chemical data
Formula C19H30O2
290.440 g/mol
 Yes (what is this?)  (verify)
Not to be confused with androstenone.

Androsterone, or 3α-hydroxy-5α-androstan-17-one, is an endogenous steroid hormone and weak androgen with a potency that is approximately 1/7 that of testosterone.[1] In addition, it can be converted to dihydrotestosterone (DHT) from 3α-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase, bypassing conventional intermediates such as androstenedione and testosterone, and as such, can be considered to be a metabolic intermediate in its own right.[2][3] Androsterone is also known to be an inhibitory androstane neurosteroid,[4][5] acting as a positive allosteric modulator of the GABAA receptor,[6] and possesses anticonvulsant effects.[7] The unnatural enantiomer of androsterone is more potent as a positive allosteric modulator of GABAA receptors and as an anticonvulsant than the natural form. [8] Androsterone's 3β-isomer is epiandrosterone, and its 5β-epimer is etiocholanolone.

History

It was first isolated in 1931, by Adolf Friedrich Johann Butenandt and Kurt Tscherning. They distilled over 17,000 liters (3,700 imp gal; 4,500 US gal) of male urine, from which they got 50 milligrams (0.77 gr) of crystalline androsterone, which was sufficient to find that the chemical formula was very similar to estrone.

Sources

Androsterone has been shown to naturally occur in pine pollen and is well known in many animal species.[9]

Biological role

Androsterone is generally 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.[7]

Synthesis

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 5α- and 5β-androstanediol, which are subsequently converted by 17β-hydroxyteroid dehydrogenase to androsterone and etiocholanolone, respectively. Androsterone and etiocholanolone can also be formed from androstenedione via the action of 5α- and 5β-reductase forming 5α- and 5β-androstane-3,17-dione which are then converted to androsterone and etiocholanolone by 3α- and 3β-hydroxysteroid dehydrogenase.[7]

See also

References

  1. ↑ Scott T (1996). Concise Encyclopedia Biology. Walter de Gruyter. p. 49. ISBN 978-3-11-010661-9. Retrieved 25 May 2012.
  2. ↑ Henderson BE; Ponder BAJ; Ross RK (13 March 2003). Hormones, Genes, and Cancer. Oxford University Press. p. 23. ISBN 978-0-19-513576-3. Retrieved 25 May 2012.
  3. ↑ Kamrath C, Hochberg Z, Hartmann MF, Remer T, Wudy SA (March 2012). "Increased activation of the alternative "backdoor" pathway in patients with 21-hydroxylase deficiency: evidence from urinary steroid hormone analysis". The Journal of Clinical Endocrinology and Metabolism 97 (3): E367–75. doi:10.1210/jc.2011-1997. PMID 22170725.
  4. ↑ Reddy DS, Rogawski MA (2012). "Neurosteroids — Endogenous Regulators of Seizure Susceptibility and Role in the Treatment of Epilepsy". In Noebels JL, Avoli M, Rogawski MA et al. Jasper's Basic Mechanisms of the Epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US).
  5. ↑ Reddy DS (2010). "Neurosteroids: endogenous role in the human brain and therapeutic potentials". Prog. Brain Res. 186: 113–37. doi:10.1016/B978-0-444-53630-3.00008-7. PMC 3139029. PMID 21094889.
  6. ↑ Li P, Bracamontes J, Katona BW, Covey DF, Steinbach JH, Akk G (June 2007). "Natural and enantiomeric etiocholanolone interact with distinct sites on the rat alpha1beta2gamma2L GABAA receptor". Mol. Pharmacol. 71 (6): 1582–90. doi:10.1124/mol.106.033407. PMID 17341652.
  7. ↑ 7.0 7.1 7.2 Kaminski RM, Marini H, Kim WJ, Rogawski MA (June 2005). "Anticonvulsant activity of androsterone and etiocholanolone". Epilepsia 46 (6): 819–27. doi:10.1111/j.1528-1167.2005.00705.x. PMC 1181535. PMID 15946323.
  8. ↑ Zolkowska D, Dhir A, Krishnan K, Covey DF, Rogawski MA (September 2014). "Anticonvulsant potencies of the enantiomers of the neurosteroids androsterone and etiocholanolone exceed those of the natural forms". Psychopharmacology (Berl) 231 (17): 3325–32. doi:10.1007/s00213-014-3546-x. PMC 4134984. PMID 24705905.
  9. ↑ Janeczko A, Skoczowski A (2005). "Mammalian sex hormones in plants". FOLIA HISTOCHEMICA ET CYTOBIOLOGICA 43 (2): 71–79.

External links