Mesenchymal-epithelial interactions and transforming growth factor-beta expression during mouse prostate morphogenesis.

To explore the role of transforming growth factor-beta (TGF beta) isoforms and other growth-related genes during prostate morphogenesis in the mouse, we examined mRNA levels in fetal day 17 urogenital sinus, mesenchyme (UGM), and epithelium (UGE) as well as in the ventral, dorsal, and anterior lobes of the adult prostate. In addition, we used antiserum specific for extracellular TGF beta 1 in immunohistochemical studies to localize accumulation of the TGF beta 1 isozyme in the above tissues as well as those derived from fetal day 19 and neonatal mouse prostate. Differential patterns of expression in fetal and adult tissues were seen. TGF beta 1, -beta 2, and -beta 3 expression was substantially elevated in UGM compared to that in UGE, yet only TGF beta 1, not TGF beta 2 or TGF beta 3, mRNA levels were sustained in adult prostate tissues. High levels of accumulation of TGF beta 1 were demonstrated by immunohistochemistry in the mesenchymal compartment compared to those in the epithelial compartment throughout development. Interestingly, the highest levels of TGF beta 1 appeared in areas of active epithelial duct formation and delineated the mesenchymal architectural changes necessary for ductal network formation. Additional studies revealed that levels of mRNAs for other genes involved in tissue remodeling and growth were also elevated in UGM compared to those in UGE. Tissue plasminogen activator, urokinase plasminogen activator, androgen receptor, and c-myc mRNA levels were also elevated in UGM compared to UGE. Interestingly, whereas tissue plasminogen activator mRNA levels, like those of TGF beta 2 and -beta 3, were barely detectable in adult prostatic tissues, mRNA levels for urokinase plasminogen activator, androgen receptor, and c-myc were readily detected and expressed in a lobe-specific fashion. Overall, these data indicate that expression of TGF beta 1 isoforms and other growth-related genes is associated with mesenchymal cells in areas of active morphogenesis during prostate development and provide objective molecular and cellular information regarding mediators of mesenchymal-epithelial interactions in prostate.