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 alpha-reductase inhibitor, 4-MAPC, and the antiandrogen, cyproterone acetate (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 experiment 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. 3H-thymidine incorporation into VP DNA was increased in castrated animals treated with TP, and 4-MAPC and CA reduced uptake. In experiment 3, animals were treated for 14 days with the 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 similar to that in intact animals. DNA was not reduced by 4-MAPC, but was reduced 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 inhibitory effect than 4-MAPC on DNA synthesis. A major reason why castration reduces DNA more than either 4-MAPC or CA is that neither of these agents was able to increase programmed cell death to the degree seen with castration.
Shao
T C
TC
Department of Medicine, VA Medical Center, Houston, Texas 77030.
Kong
A
A
Cunningham
G R
GR
D058891:5-alpha Reductase Inhibitors; D000727:Androgen-Binding Protein / Q000235:genetics; D000818:Animals; D001378:Azasteroids; D017373:Cyproterone Acetate / Q000494:pharmacology*; D004247:DNA / Q000032:analysis; D008297:Male; D009919:Orchiectomy; D011278:Pregnanes / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects / Q000502:physiology*; D060789:Prostatein; D011506:Proteins / Q000032:analysis; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects*; D060765:Secretoglobins; D013739:Testosterone / Q000494:pharmacology; D014598:Uteroglobin; D060788:Mammaglobin B
D058891:5-alpha Reductase Inhibitors; D000727:Androgen-Binding Protein; D001378:Azasteroids; D017373:Cyproterone Acetate; D004247:DNA; D011278:Pregnanes; D060789:Prostatein; D011506:Proteins; D012313:RNA; D012333:RNA, Messenger; D060765:Secretoglobins; D013739:Testosterone; D014598:Uteroglobin; C511484:Scgb1d2 protein, rat; C511483:Scgb1d4 protein, rat; C037399:4-methyl-4-aza-3-oxopregnane-20-carboxylate; C556468:Scgb2a1 protein, rat; D060788:Mammaglobin B