3β-Androstanediol

Biological activity

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

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. Through the ERβ, 3β-androstanediol positively regulates oxytocin neurons and signaling in the paraventricular nucleus of hypothalamus, and has been found to have antidepressant, anxiolytic, cognitive-enhancing, and stress-relieving effects via this action. 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.

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.

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

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.

References

References

1. (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.
2. C.Y. Cheng. (24 October 2009). "Molecular Mechanisms in Spermatogenesis". Springer Science & Business Media.
3. (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.
4. (2002). "Recent insights into the origins of adrenal and sex steroid receptors". J. Mol. Endocrinol..
5. (1997). "Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors α and β". Endocrinology.
6. (1997). "Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta". Endocrinology.
7. (2010). "The Testosterone-Derived Neurosteroid Androstanediol Is a Positive Allosteric Modulator of GABAA Receptors". Journal of Pharmacology and Experimental Therapeutics.
8. (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.
9. (2012). "The ERβ Ligand 5α-androstane, 3β,17β-diol (3β-diol) Regulates Hypothalamic Oxytocin (Oxt) Gene Expression". Endocrinology.
10. (2013). "The Androgen Metabolite, 5α-Androstane-3β,17β-Diol (3β-Diol), Activates the Oxytocin Promoter Through an Estrogen Receptor-β Pathway". Endocrinology.
11. (2008). "An estrogenic effect of 5α-androstane-3β, 17β-diol on the behavioral response to stress and on CRH regulation". Neuropharmacology.
12. (2008). "Androgens with activity at estrogen receptor beta have anxiolytic and cognitive-enhancing effects in male rats and mice". Hormones and Behavior.
13. (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.
14. (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.
15. (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.
16. (August 1978). "The determination of 5alpha-androstane-3alpha, 17beta-diol in human plasma by radioimmunoassay". Acta Endocrinologica.
17. (February 2015). "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..
18. (June 1956). "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..
19. (February 2012). "17α-alkynyl 3α, 17β-androstanediol non-clinical and clinical pharmacology, pharmacokinetics and metabolism". Invest New Drugs.