In Vivo Effects on Spermatogenesis and In Vitro Metabolism of 5α-Androstan-3β,17β-Diol by Testes, Prostate Glands and Seminal Vesicles

It has been shown that 17β-hydroxy-5α-androstan-3-one (dihydrotestosterone, DHT), an irreversible metabolite of testosterone, is capable of maintaining spermatogenesis and sex accessory organs of adult rats. The same property has been displayed by 5α-androstan-3α,17β-diol (3α-diol). We have studied the effects of 5α-androstan-3β,17β-diol (3β-diol) in hypophysectomized rats. This steroid is also capable of maintaining spermatogenesis as well as the accessory glands of hypophysectomized rats. These effects of 3β-diol are quantitatively better than with 3α-diol. Incubation of teased testicular tissue, prostate glands and seminal vesicles with tritiated 3β-diol showed that 3β-diol is preferentially converted to 3α-diol in the testis and DHT in the prostate glands but is not metabolized by the seminal vesicles. This would tend to indicate that the biological activity may be attributed to any one of the 5α-reduced metabolites since the testes and prostate glands can metabolize 3β-diol and the seminal vesicles could get the appropriate form of the steroid by conversion at a peripheral site with transport to the seminal vesicles. Incubation of testicular tissue with tritiated 3β-diol and a steroidal inhibitor of 3β-hydroxysteroid dehydrogenase showed 90% inhibition of 3β-diol metabolism. In vivo studies with this inhibitor are underway to assess if 3β-diol is biologically active without being converted to other steroids.