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 measure d: epithelial area, epithelial perimeter, node number, and form factor. Nin e natural and synthetic androgens were tested for their effectiveness in in ducing postnatal prostatic development using 808 newborn rat APs in 68 dose -response experiments. Based on these studies it was shown that testosteron e (T) was slightly more effective than dihydrotestosterone (DHT) in support ing ductal branching morphogenesis in the developing rat AP. Furthermore, t he activity of T could not be accounted for simply by conversion of T to DH T. Synthetic androgens, 7 alpha-methyl-19-nortestosterone and methyltrienol one (R1881), which cannot be 5 alpha-reduced to DHT, also induced extensive ductal branching and elicited responses less than those to T and not stati stically different from those to DI-IT. This suggests that although DHT is sufficient for prostatic development, it is not necessary for postnatal duc tal branching morphogenesis and growth of the prostate. 5 alpha-Androstan-3 alpha,17 beta-diol was particularly potent in inducing ductal branching, e liciting a response greater than or comparable to those of T and DHT. Andro sterone, 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 e xtent than either T or DHT. These studies challenge the assumption that DHT is essential for prostatic development, specifically during ductal branchi ng morphogenesis of the neonatal rat prostate.