[Prostatic development, cytodifferentiation and growth: epithelial-mesenchymal interaction and heterogeneity of...

Prostatic growth and hormonal effects on the prostate play a basic role in the pathogenesis of abnormal proliferative diseases (i.e. benign prostatic hyperplasia and prostatic carcinoma). During the embryonic period, the prostate is organized through the budding and branching of the epithelial cords into the urogenital sinus mesenchyme. The urogenital sinus mesenchyme has an inductive potential for the prostatic epithelial development and cytodifferentiation under the influence of androgen and an epithelial-mesenchymal interaction. In this interaction, mesenchymal cells are considered as a mediator of hormonal action on epithelial cells. Postnatal prostatic growth is obtained further ductal branching morphogenesis and regulated by the epithelial-mesenchymal interaction, androgen, and epithelial/mesenchymal ratio. Castration-induced degeneration, and androgen-induced regeneration of the glandular architecture of the mouse prostate were investigated by microdissection techniques that permitted precise quantitation of the numbers of the terminal ductal tips and ductal branch-points. During the first 15 days after birth, active branching morphogenesis occurred as a result of focally high levels of DNA synthesis confined almost exclusively to the distal tips of the branching ducts. Following castration about 35% of the ductal tips and branch-points were lost in distal regions (usually near the capsule). By contrast, in more proximal regions of the prostate the ducts survived in an atrophic condition. The lost distal ductal morphology completely regenerated following administration of testosterone propionate (TP) to the castrated males. Whole-mount autoradiography demonstrated that labelling intensity reached a maximum on the third day of TP treatment in distal ductal areas. Recognition of the mesenchymal-epithelial interaction and heterogeneities in the morphogenesis, androgen dependency, and DNA synthetic activity within the prostatic architecture is fundamental to understanding the mechanism of androgenic regulation of normal or abnormal prostatic growth and development.