4‐MAPC, a 5α‐Reductase Inhibitor, Reduces Rat Ventral Prostate Weight, DNA, and Prostatein Concentrations

Abstract

ABSTRACT: Several compounds, such as 4‐MAPC (4‐methyl‐3‐oxo‐4‐aza‐5α‐pregnane‐20‐carboxylate), that inhibit conversion of testosterone (T) to dihydrotestosterone (DHT) by 5α‐reductase have been demonstrated to reduce prostate size in rats and dogs. The current studies were undertaken to determine if this effect is due to a reduction in cell number, in epithelial cell synthetic activity, or both. Eight‐week‐old intact rats were treated daily for 14 days with sesame seed oil, 4‐MAPC (10 mg/kg), 4‐MAPC + testosterone propionate (TP, 1 mg/kg), or 4‐MAPC + TP (3 mg/kg). Rats were killed 24 hours after the last injection. In the animals treated only with 4‐MAPC, ventral prostate weight was reduced 37%, but the 14% reduction in total DNA was not significant. The mean intraprostatic concentration of prostatein, a major secretory protein, was reduced 45% (P < 0.05). The 3 mg/kg dose of TP increased ventral prostate weight, prostatein concentrations, and acid phosphatase activity, even though DNA/ventral prostate was similar to that in control animals. These observations indicate that the reduction in ventral prostate weight in adult rats is due in part to a reduction in cell number, but the primary effect was due to a reduction in synthetic activity, and possibly atrophy of the epithelial cells. Furthermore, TP in pharmacologic doses increased ventral prostate weight and synthetic activity without increasing DNA.