Binding and metabolism of 5alpha-androstane-3alpha, 17 beta-diol and of 5alpha-androstane-3beta, 17 beta-diol in the prostate, seminal vesicles and plasma of male rats: studies in vivo and in vitro.

Binding of 5alpha-androstane-3alpha, 17 beta-diol (3alpha-diol) and 5alpha-androstane-3beta,-17 beta-diol (3beta-diol) in vivo and in vitro to the 100 000 g cytosol fraction of the rat prostate and seminal vesicles as well as to plasma was studied by agargel electrophoresis and sucrose density gradient ultracentrifugation and the results compared with the corresponding findings for 5alpha-dihydrotestosterone (5alpha-DHT). The metabolism of 3alpha-diol and 3beta-diol was also investigated by thin-layer chromatography. The following results were obtained: (1) A specific binding of 3alpha-diol and 3beta-diol by the cytosols could not be demonstrated in vitro, while 5alpha-DHT was specifically bound. (2) In plasma, 3alpha-diol was extensively bound, 3beta-diol less extensively bound, while 5alpha-DHT remained unbound. (3) After intravenous injection of 3alpha-diol, specifically bound radioactivity, increasing within 30 min, was found in the prostate cytosol, while after 3beta-diol injection no binding occurred. (4) Parallel to the increased binding, the total radioactivity in the prostate accumulated within 30 min after 3alpha-diol injection, the uptake being 5-3 times higher than in skeletal muscle. However after 3beta-diol injection, total radioactivity decreased in the prostate within 30 min, the uptake being only 1-5 times higher than in skeletal muscle. (5) One minute after injection of 3alpha-diol, 53% of the extracted radioactivity in the prostate had been converted to 5alpha-DHT, this increased within 30 min to 81%. Thirty minutes after the injection of 3beta-diol, about 32% of the extracted radioactivity in the prostate had been converted to 5alpha-DHT. (6) From the in-vivo and in-vitro experiments it was concluded that 3alpha-diol exerts its biological effects mainly by its conversion into 5alpha-DHT.