FK143, A NOVEL NONSTEROIDAL INHIBITOR OF STEROID 5-ALPHA-REDUCTASE .2. IN-VIVO EFFECTS ON RAT AND DOG PROSTATES

FR143 is a nonsteroidal new inhibitor of steroid 5 alpha-reductase, an enzyme which converts testosterone into 5 alpha-dihydrotestosterone ( DHT). We studied in vivo effects of FK143 on rat and dog prostates. FK 143 was orally administered to mature male rats for 14 days. At doses above 1mg/kg, FK143 significantly reduced the wet weights of the ventr al prostate and seminal vesicle, but showed no effects on those of the epididymis, testis, and adrenal. Growth of ventral prostate and semin al vesicle was induced by the subcutaneous injection of testosterone p ropionate (TP) in the castrated young rats and was reduced by FR143 ad ministration at doses above 3.2 mg/kg, while growth induced by 5 alpha -dihydrotestosterone propionate (DHTP) was not affected. FK143 had no binding affinity for the rat androgen receptor. FR143 showed neither e strogenic and antiestrogenic effects on the rat uterus nor androgenic effect on the rat prostate. Concentration of testosterone and DHT in t he rat and dog prostates were measured by GC-MS, and administration of 10 mg/kg of FK143 significantly reduced the intraprostatic concentrat ion of DHT. These results indicate that FK143 reduced the prostate gro wth by inhibiting 5 alpha-reductase activities in the prostates.