EFFECTS OF 4-MAPC, A 5-ALPHA-REDUCTASE INHIBITOR, AND CYPROTERONE-ACETATE ON REGROWTH OF THE RAT VENTRAL PROSTATE

Inhibitors of 5 alpha-reductase activity cause less involution of the rat ventral prostate (VP) than does castration. Studies were conducted in adult Sprague Dawley rats to evaluate the effects of a potent 5 al pha-reductase inhibitor, 4-MAPC, and the antiandrogen, cyproterone ace tate (CA), on DNA synthesis and apoptosis. In experiment 1, VP weight fell 33%, 53%, and 83%, and DNA per ventral prostate was reduced 24%, 46%, and 71%, by 4-MAPC, CA, and castration, respectively. In experime nt 2, adult rats were castrated, and the VP involuted for 7 days prior to 3 daily injections of testosterone propionate (TP; 1 mg/kg/d) +/- 10 mg/kg/d of 4-MAPC or CA. H-3-thymidine incorporation into VP DNA wa s increased in castrated animals treated with TP, and 4-MAPC and CA re duced uptake. In experiment 3, animals were treated for 14 days with t he same protocol as that used in experiment 2. VP weight was increased in all animals treated with TP when compared with castration, and was reduced by both 4-MAPC and CA. DNA in rats treated with TP was simila r to that in intact animals. DNA was not reduced by 4-MAPC, but was re duced by CA. The mRNA for TRPM-2, a marker of apoptosis, was increased only in untreated castrated rats. It appears that CA has a greater in hibitory effect than 4-MAPC on DNA synthesis. A major reason why castr ation reduces DNA more than either 4-MAPC or CA is that neither of the se agents was able to increase programmed cell death to the degree see n with castration. (C) 1994 Wiley-Liss, Inc.