Prostatic effects of a nonsteroidal antiandrogen.
The possible mechanisms for the antiprostatic effects of a nonsteroidal antiandrogen, SCH 13521 (4'-nitro-3'-trifluoromethylisobutyranilide), were investigated in rats and dogs. The influence of administered SCH 13521 on the deposition of the radioactivity associated with labeled testosterone, dihydrotestosterone, and estriol (E-3) in the prostate and other tissues of the dog, and rat was determined in short term experiments. SCH 13521 definitely interfered with the localization of the radioactivity of these steroids in the prostate and indicated a competitive situation between SCH 13521 and the steroids. Even though in vitro binding data were generally in accord with in vivo results, he descrepancies regarding E-3 and the more intense effects of SCH 13521 observed in vivo, as compared to those in vitro, lead us to suggest that a metabolite of the compound may also play an important competitive role in vivo. Of particular interest was the competition between SCH 13521 and estrogens in vitro (estradiol-17-beta) and in vivo (E-3). Sch 13521 greatly decreased the volume of prostatic secretion whereas id minor effects on prostatic 5-alpha-reductase and arginase activities. The latter is surprising, since both enzymes are very highly androgen-dependent. Thus, even though the mechanisms of action of SCH 13521 on the prostate may involve competition with androgens at the cellular level, we think that its competition with some estrogens points to a more complicated action than observed with other antiandrogens.
D000726:Androgen Antagonists; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D001119:Arginase / Q000378:metabolism; D001667:Binding, Competitive; D002250:Carbon Radioisotopes; D002369:Castration; D013196:Dihydrotestosterone / Q000378:metabolism; D004285:Dogs; D004958:Estradiol / Q000378:metabolism; D004964:Estriol / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D008297:Male; D009574:Nitro Compounds / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013739:Testosterone / Q000378:metabolism; D014316:Tritium
D000726:Androgen Antagonists; D000813:Anilides; D002250:Carbon Radioisotopes; D006845:Hydrocarbons, Fluorinated; D009574:Nitro Compounds; D013196:Dihydrotestosterone; D014316:Tritium; D013739:Testosterone; D004958:Estradiol; D010088:Oxidoreductases; D001119:Arginase; D004964:Estriol