IN VITRO EFFECTS OF AN AROMATASE INHIBITOR ON 5α-REDUCTASE ACTIVITY IN HUMAN HYPERTROPHIC PROSTATIC TISSUE

Abstract

To determine the effects of 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the in vitro conversion of testosterone (T) to 5α-androstan-17β-ol-3-one (dihydrotestosterone, DHT), 5α-androstan-3α,17β-diol and 5α-androstan- 3β,17β-diol (diols), human benign hypertrophic prostatic (BPH) tissue was incubated with 4^-14;C-T as substrate, in the presence of 4-OH-A (10^-8 to 10^-6); the amounts of the 5α-reduced metabolites formed were quantitated. The effects of 4-OH-A were compared with those of 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one (4-MA), a known inhibitor of the 5α-reductase. In the absence of 4-OH-A and 4-MA, human BPH tissue converted T to DHT and the diols readily. Both 4-OH-A and 4-MA induced significant and dose-related decreases in the formation of both DHT and the diols. The degree of inhibition induced by the different concentrations of 4-OH-A and 4-MA were 31, 4l, 72% and 57, 87, 97%, respectively. The decreased formation of the diols was a consequence of the decreased availability of DHT (the immediate precursor of the diols) and was not due to direct effects of the inhibitors on the 3-hydroxysteroid dehydrogenases; both 4-OH-A and 4-MA were totally unable to modify the conversion of DHT to the diols, when 4-l4C-DHT w a s used as substrate. Thus, 4-OH-A inhibits the process of 5α-reduction of T in BPH tissue. This molecule might represent a potential new agent for the prevention and/or treatment of human BPH.