Efficacy of various natural and synthetic androgens to induce ductal branching morphogenesis in the developing anterior rat prostate

The studies presented herein quantitated ductal branching morphogenesis in the anterior prostate (AP) of the newborn rat. Four parameters were measured: epithelial area, epithelial perimeter, node number, and form factor. Nine natural and synthetic androgens were tested for their effectiveness in inducing postnatal prostatic development using 808 newborn rat APs in 68 dose-response experiments. Based on these studies it was shown that testosterone (T) was slightly more effective than dihydrotestosterone (DHT) in supporting ductal branching morphogenesis in the developing rat AP. Furthermore, the activity of T could not be accounted for simply by conversion of T to DHT. Synthetic androgens, 7 alpha-methyl-19-nortestosterone and methyltrienolone (R1881), which cannot be 5 alpha-reduced to DHT, also induced extensive ductal branching and elicited responses less than those to T and not statistically different from those to DI-IT. This suggests that although DHT is sufficient for prostatic development, it is not necessary for postnatal ductal branching morphogenesis and growth of the prostate. 5 alpha-Androstan-3 alpha,17 beta-diol was particularly potent in inducing ductal branching, eliciting a response greater than or comparable to those of T and DHT. Androsterone, androstanedione, 5 alpha-androstan-3 beta,17 beta-diol and 5 beta-androstan-3 alpha, 17 beta-diol induced ductal branching, but to a lesser extent than either T or DHT. These studies challenge the assumption that DHT is essential for prostatic development, specifically during ductal branching morphogenesis of the neonatal rat prostate.