5α-Androstane-3β,17β-diol

5α-Androstane-3β,17β-diol
Names
IUPAC name
(3β,5α,17β)-Androstane-3,17-diol
Systematic IUPAC name
(1S,2S,5S,7S,10R,11S,14S,15S)-2,15-Dimethyltetracyclo[8.7.0.02,7.011,15]heptadecane-5,14-diol
Other names
3β-Androstanediol; 3β-Diol
Identifiers
ChEMBL ChEMBL316048
ChemSpider 211834
Jmol interactive 3D Image
PubChem 242332
Properties
C19H32O2
Molar mass 292.46 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

5α-Androstane-3β,17β-diol, also called 3β-androstanediol, and often shortened to 3β-diol, is an endogenous steroid hormone. It is a 5α-reduced and 17β-hydroxylated metabolite of dehydroepiandrosterone (DHEA) as well as a 3β-hydroxylated metabolite of dihydrotestosterone (DHT). 3β-Diol is a selective, potent, high-affinity full agonist of the ERβ, and hence, an estrogen.[1] It has higher affinity for this receptor than estradiol.[1] In contrast to ERβ, 3β-diol does not bind to the androgen receptor (AR).[2] 3β-Diol has been reported to also bind to ERα with low nanomolar affinity, with several-fold lower affinity relative to ERβ.[3][4] Unlike its 3α-isomer, 3α-androstanediol (3α-diol), 3β-diol does not bind to the GABAA receptor.[5]

3β-Diol appears to be the endogenous ligand of ERβ in the prostate gland, and as a result of activation of the ERβ, 3β-diol has antiproliferative effects against prostate cancer cells.[6] Through the ERβ, 3β-diol positively regulates oxytocin neurons and signaling in the paraventricular nucleus of hypothalamus (PVN),[7][8] and has been found to have antidepressant,[9] anxiolytic,[10] cognitive-enhancing,[10] and stress-relieving effects via this action.[11][12] Androgens, including testosterone and dihydrotestosterone (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-diol rather than to activation of the AR.[11][12][13]

A determination of the circulating levels of 3β-diol in humans found concentrations of 239 ± 76 pg/ml and 82 ± 45 pg/ml of the compound in normal male and female serum, respectively.[14]

An orally active synthetic analogue of 3β-diol, 17α-ethynyl-5α-androstane-3α,17β-diol (HE3235, Apoptone), was formerly under investigation for the treatment of prostate cancer and breast cancer.[15]

See also

References

  1. 1 2 C.Y. Cheng (24 October 2009). Molecular Mechanisms in Spermatogenesis. Springer Science & Business Media. pp. 259–. ISBN 978-0-387-09597-4.
  2. ↑ Oliveira AG, Coelho PH, Guedes FD, Mahecha GA, Hess RA, Oliveira CA (December 2007). "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. doi:10.1016/j.steroids.2007.08.001. PMID 17854852.
  3. ↑ Baker ME (2002). "Recent insights into the origins of adrenal and sex steroid receptors". J. Mol. Endocrinol. 28 (3): 149–52. doi:10.1677/jme.0.0280149. PMID 12063181.
  4. ↑ 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.
  5. ↑ 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. PMC 2939675. PMID 20551294.
  6. ↑ Weihua Z, Lathe R, Warner M, Gustafsson JA (October 2002). "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. doi:10.1073/pnas.162477299. PMC 129718. PMID 12370428.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. 1 2 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.
  11. 1 2 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.
  12. 1 2 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. doi:10.3389/fendo.2011.00065. ISSN 1664-2392.
  13. ↑ 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.
  14. ↑ Laband P, Tresguerres JA, Lisboa BP, Volkwein U, Tamm J (August 1978). "The determination of 5alpha-androstane-3alpha, 17beta-diol in human plasma by radioimmunoassay". Acta Endocrinologica 88 (4): 778–86. PMID 581118.
  15. ↑ Ahlem C, Kennedy M, Page T, Bell D, Delorme E, Villegas S, Reading C, White S, Stickney D, Frincke J (2012). "17α-alkynyl 3α, 17β-androstanediol non-clinical and clinical pharmacology, pharmacokinetics and metabolism". Invest New Drugs 30 (1): 59–78. doi:10.1007/s10637-010-9517-0. PMID 20814732.
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