Metabolism.docx

3α-Androstanediol (often abbreviated as 3α-diol), also known as 5α-androstane-3α,17β-diol, is an endogenous inhibitory androstane neurosteroid and weak androgen, and a major metabolite of dihydrotestosterone (DHT).[1][2][3] As a neurosteroid, it acts as a potent positive allosteric modulator of the GABAA receptor,[4] and has been found to have rewarding,[5][6] anxiolytic,[7] prosexual,[8] and anticonvulsant effects.[9][10] As androgens such as testosterone and DHT are known to have many of the same effects as 3α-diol and are converted into it in vivo, it is thought that this compound may in part be responsible for said effects.[5][6][7][10] Relative to its isomer 3βandrostanediol, which is a potent estrogen, 3α-androstanediol has substantially lower, though still significant affinity for the estrogen receptors, with a several-fold preference for ERβ over ERα.[11][12] It has approximately 0.07% and 0.3% of the affinity of estradiol at the ERα and ERβ, respectively.[13]

An orally active synthetic analogue of 3α-androstanediol, 17α-ethynyl-5α-androstane-3α,17β-diol (HE-3235, Apoptone), was formerly under investigation for the treatment of prostate cancer and breast cancer.[14]