Effect of a new 5 alpha-reductase inhibitor on size, histologic characteristics, and androgen concentrations of the canine prostate.
Mature male beagles were used in studies designed to determine the effect of the steroidal 5 alpha-reductase inhibitor 17 beta-N,N-diethylcarbamoyl-4-aza-4-methyl-5 alpha-androstan-3-one (4-MA) on size, histology, and androgen concentration of the prostate. Subcutaneous administration of 3 or 15 mg/kg/day for 43 days caused a sharp decline in prostate volume. flattening of prostatic epithelial cells, vacuolization of the cytoplasm and pycnosis of the nuclei. Whereas serum testosterone levels remained normal in dogs injected with 3 mg/kg/day, they were lower in those that received 15 mg/kg/day. Concentration of both testosterone and 5 alpha-dihydrotestosterone were reduced in the prostates of dogs that had received either 3 or 15 mg/kg/day of 4-MA. The 15 mg/kg/day level also appeared to adversely affect spermatogenesis. In a 43-day study, 4-MA given orally once each day at levels of 0.1, 0.3, or 1 mg/kg failed to cause a significant decrease in prostate volume. However, daily divided oral doses totaling 1 or 3 mg/kg were given in a 42-day test and both treatment levels produced significant reductions in prostate size.
D058891:5-alpha Reductase Inhibitors; D000818:Animals; D001284:Atrophy / Q000139:chemically induced; D001378:Azasteroids / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000032:analysis* / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects; D013260:Steroids, Heterocyclic / Q000494:pharmacology*; D013739:Testosterone / Q000032:analysis*
D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D013260:Steroids, Heterocyclic; D013196:Dihydrotestosterone; D013739:Testosterone; C031563:17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one; D010088:Oxidoreductases