EFFECTS OF 5-ALPHA-REDUCTASE INHIBITORS ON INTRAPROSTATIC ANDROGENS IN THE RAT

FCE 27837 is a novel inhibitor of 5 alpha-reductase, the enzyme respon sible for the conversion of testosterone (T) to 5 alpha-dihydrotestost erone (DHT). The compound caused inhibition of human and rat prostatic enzymes, with IC50 values of 51 and 60 nM, respectively. The in vivo effect of FCE 27837 on 5 alpha-reductase was evaluated in adult male r ats, treated orally at 10 mg/kg/day for 10 days. The compound caused 3 3 and 42% reductions in ventral prostate and seminal vesicle weights, respectively. The prostatic content of DHT, measured 6 h after the 10t h dose of FCE 27837, was reduced by 75%, whereas T content increased b y 442%. Similar effects were observed with 10 mg/kg/day of finasteride , whereas epristeride, tested at the same oral dose, was found to be t he least effective compound, decreasing prostate weight by 22% and DHT content by 46%. Castration caused >90% reductions in prostatic weight and prostatic DHT.