Chemistry:3β-Androstanediol

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3β-Androstanediol
3beta-Androstanediol.svg
Names
IUPAC name
5α-Androstane-3β,17β-diol
Systematic IUPAC name
(1S,3aS,3bR,5aS,7S,9aS,9bS,11aS)-9a,11a-Dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,7-diol
Other names
3β-Androstanediol; 3β-Diol; Maxterone
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
UNII
Properties
C19H32O2
Molar mass 292.463 g·mol−1
Melting point 168–170 °C (334–338 °F; 441–443 K)[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references
Tracking categories (test):

3β-Androstanediol, also known as 5α-androstane-3β,17β-diol, and sometimes shortened in the literature to 3β-diol, is an endogenous steroid hormone and a metabolite of androgens like dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT).

Biological activity

3β-Androstanediol is a selective, high-affinity agonist of the ERβ, and hence, an estrogen.[2] In contrast to ERβ, 3β-androstanediol does not bind to the androgen receptor (AR).[3] 3β-Androstanediol has been reported to also bind to ERα with low nanomolar affinity, with several-fold lower affinity relative to ERβ.[4][5] It has approximately 3% and 7% of the affinity of estradiol at the ERα and ERβ, respectively.[6] Unlike 3α-androstanediol, 3β-androstanediol does not bind to the GABAA receptor.[7]

3β-Androstanediol may be the primary endogenous ligand of ERβ in the prostate gland, and as a result of activation of the ERβ, 3β-androstanediol has antiproliferative effects against prostate cancer cells.[8] Through the ERβ, 3β-androstanediol positively regulates oxytocin neurons and signaling in the paraventricular nucleus of hypothalamus,[9][10] and has been found to have antidepressant,[11] anxiolytic,[12] cognitive-enhancing,[12] and stress-relieving effects via this action.[13][14] Androgens, including testosterone and DHT, are known to downregulate the hypothalamic-pituitary-adrenal axis, and this has been found to be due in part or full to their conversion into 3β-androstanediol rather than to activation of the AR.[13][14][15]

Biochemistry

3β-Androstanediol is a 5α-reduced and 17β-hydroxylated metabolite of dehydroepiandrosterone (DHEA) as well as a 3β-hydroxylated metabolite of DHT (and by extension of testosterone).

A determination of the circulating levels of 3β-androstanediol in humans found concentrations of 239 ± 76 pg/ml and 82 ± 45 pg/ml of the compound in normal male and female serum, respectively.[16]

3β-Androstanediol shows high affinity for sex hormone-binding globulin (SHBG), similar to that of DHT.[17]

Chemistry

3β-Androstanediol, also known as 5α-androstane-3β,17β-diol, is a naturally occurring androstane steroid and a structural analogue of DHT (5α-androstan-17β-ol-3-one). A notable epimer of 3β-androstanediol is 3α-androstanediol.

17α-Ethynyl-3β-androstanediol is a 17α-substituted derivative of 3β-androstanediol and is an estrogen similarly.[18][19]

References

  1. ↑ Wang, Xingbin; Liu, Hui; Yan, Peiyun; Liu, Jinliang; Li, Yan; Sun, Qian; Wang, Cunde (1 May 2011). "Simultaneously rapid deprotection of 3-acyloxy groups and reduction of D-ring ketones (nitrile) of steroids using DIBAL-H/NiCl2". Journal of Chemical Research 35 (5): 291–293. doi:10.3184/174751911X13050949941793. 
  2. ↑ C.Y. Cheng (24 October 2009). Molecular Mechanisms in Spermatogenesis. Springer Science & Business Media. pp. 259–. ISBN 978-0-387-09597-4. https://books.google.com/books?id=tdpVNN80_r0C&pg=PA259. 
  3. ↑ "5alpha-Androstane-3beta,17beta-diol (3beta-diol), an estrogenic metabolite of 5alpha-dihydrotestosterone, is a potent modulator of estrogen receptor ERbeta expression in the ventral prostrate of adult rats". Steroids 72 (14): 914–22. December 2007. doi:10.1016/j.steroids.2007.08.001. PMID 17854852. 
  4. ↑ "Recent insights into the origins of adrenal and sex steroid receptors". J. Mol. Endocrinol. 28 (3): 149–52. 2002. doi:10.1677/jme.0.0280149. PMID 12063181. https://cloudfront.escholarship.org/dist/prd/content/qt8qd4j1k2/qt8qd4j1k2.pdf. 
  5. ↑ Kuiper, George G. J. M.; Carlsson, Bo; Grandien, Kaj; Enmark, Eva; Häggblad, Johan; Nilsson, Stefan; Gustafsson, Jan-Åke (1997). "Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors α and β". Endocrinology 138 (3): 863–870. doi:10.1210/endo.138.3.4979. ISSN 0013-7227. PMID 9048584. 
  6. ↑ "Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta". Endocrinology 138 (3): 863–70. 1997. doi:10.1210/endo.138.3.4979. PMID 9048584. 
  7. ↑ Reddy, D. S.; Jian, K. (2010). "The Testosterone-Derived Neurosteroid Androstanediol Is a Positive Allosteric Modulator of GABAA Receptors". Journal of Pharmacology and Experimental Therapeutics 334 (3): 1031–1041. doi:10.1124/jpet.110.169854. ISSN 0022-3565. PMID 20551294. 
  8. ↑ "An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth". Proceedings of the National Academy of Sciences of the United States of America 99 (21): 13589–94. October 2002. doi:10.1073/pnas.162477299. PMID 12370428. Bibcode: 2002PNAS...9913589W. 
  9. ↑ Sharma, Dharmendra; Handa, Robert J.; Uht, Rosalie M. (2012). "The ERβ Ligand 5α-androstane, 3β,17β-diol (3β-diol) Regulates Hypothalamic Oxytocin (Oxt) Gene Expression". Endocrinology 153 (5): 2353–2361. doi:10.1210/en.2011-1002. ISSN 0013-7227. PMID 22434086. 
  10. ↑ Hiroi, Ryoko; Lacagnina, Anthony F.; Hinds, Laura R.; Carbone, David G.; Uht, Rosalie M.; Handa, Robert J. (2013). "The Androgen Metabolite, 5α-Androstane-3β,17β-Diol (3β-Diol), Activates the Oxytocin Promoter Through an Estrogen Receptor-β Pathway". Endocrinology 154 (5): 1802–1812. doi:10.1210/en.2012-2253. ISSN 0013-7227. PMID 23515287. 
  11. ↑ Huang, Q; Zhu, H; Fischer, D; Zhou, J (2008). "An estrogenic effect of 5α-androstane-3β, 17β-diol on the behavioral response to stress and on CRH regulation". Neuropharmacology 54 (8): 1233–1238. doi:10.1016/j.neuropharm.2008.03.016. ISSN 0028-3908. PMID 18457850. 
  12. ↑ 12.0 12.1 Frye, C; Koonce, C; Edinger, K; Osborne, D; Walf, A (2008). "Androgens with activity at estrogen receptor beta have anxiolytic and cognitive-enhancing effects in male rats and mice". Hormones and Behavior 54 (5): 726–734. doi:10.1016/j.yhbeh.2008.07.013. ISSN 0018-506X. PMID 18775724. 
  13. ↑ 13.0 13.1 Handa, R. J.; Weiser, M. J.; Zuloaga, D. G. (2009). "A Role for the Androgen Metabolite, 5α-Androstane-3β,17β-Diol, in Modulating Oestrogen Receptor β-Mediated Regulation of Hormonal Stress Reactivity". Journal of Neuroendocrinology 21 (4): 351–358. doi:10.1111/j.1365-2826.2009.01840.x. ISSN 0953-8194. PMID 19207807. 
  14. ↑ 14.0 14.1 Handa, Robert J.; Sharma, Dharmendra; Uht, Rosalie (2011). "A Role for the Androgen Metabolite, 5alpha Androstane 3beta, 17beta Diol (3?-Diol) in the Regulation of the Hypothalamo-Pituitary?Adrenal Axis". Frontiers in Endocrinology 2: 65. doi:10.3389/fendo.2011.00065. ISSN 1664-2392. PMID 22649380. 
  15. ↑ Handa, Robert J.; Pak, Toni R.; Kudwa, Andrea E.; Lund, Trent D.; Hinds, Laura (2008). "An alternate pathway for androgen regulation of brain function: Activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5α-androstane-3β,17β-diol". Hormones and Behavior 53 (5): 741–752. doi:10.1016/j.yhbeh.2007.09.012. ISSN 0018-506X. PMID 18067894. 
  16. ↑ "The determination of 5alpha-androstane-3alpha, 17beta-diol in human plasma by radioimmunoassay". Acta Endocrinologica 88 (4): 778–86. August 1978. doi:10.1530/acta.0.0880778. PMID 581118. 
  17. ↑ "Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and α-fetoprotein". Toxicol. Sci. 143 (2): 333–48. February 2015. doi:10.1093/toxsci/kfu231. PMID 25349334. 
  18. ↑ "Uterine growth stimulating and testicular growth suppressing activities of 17alpha-ethinylandrostane-3beta, 17beta-diol, its delta 5-analog and derivatives". Proc. Soc. Exp. Biol. Med. 92 (2): 404–8. June 1956. doi:10.3181/00379727-92-22493. PMID 13350363. 
  19. ↑ "17α-alkynyl 3α, 17β-androstanediol non-clinical and clinical pharmacology, pharmacokinetics and metabolism". Invest New Drugs 30 (1): 59–78. February 2012. doi:10.1007/s10637-010-9517-0. PMID 20814732. 




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