Stromal-epithelial interactions: II. Regulation of prostatic growth by embryonic urogenital sinus mesenchyme.

Embryonic urogenital sinus mesenchyme (UGM) has been demonstrated previously to be a potent inductor of prostatic morphogenesis and functional differentiation when associated with either embryonic urogenital sinus epithelium (UGE) or urothelium derived from adult urinary bladder (ABLE) and grown in male hosts. To determine the role of mesenchyme in prostatic acinar growth, homotypic tissue recombinants of 16-day-old embryonic mouse urogenital sinus mesenchyme and epithelium (UGM mouse + UGE mouse) were prepared in which the relative amounts of UGM to UGE were varied from approximately 0.1:1 to 100:1. Recombinants were grown for 1 month in intact male hosts after which the amount of acinar growth was assessed by histological analysis and by determination of wet weight and DNA content. The latter criteria are valid measures of acinar content of histologically normal prostatic tissue because the rodent prostate is composed of greater than 80% ductal-acinar tissue. From this analysis the amount of acinar growth was found to be determined by the amount of mesenchymal tissue and was independent of the amount of epithelium utilized to prepare the tissue recombinants. Similarly, the magnitude of growth in hetero-specific rat-mouse tissue recombinants prepared with urogenital sinus epithelium or adult bladder epithelium (ABLE) and urogenital sinus mesenchyme (UGM mouse + UGE rat, UGM mouse + ABLE rat, UGM rat + UGE mouse, or UGM rat + ABLE mouse) is determined by the source of UGM. Although the initial DNA content per UGM is comparable between mouse and rat, the overall acinar growth induced by UGM rat is about 10-fold greater than that induced by UGM mouse when recombined reciprocally with UGE mouse and UGE rat, respectively. These results suggest that UGM is of fundamental importance as a regulator of prostatic epithelial growth. The relevance of this finding to the development of human benign prostatic hyperplasia is discussed.