INDUCTION OF PROSTATIC MORPHOLOGY AND SECRETION IN UROTHELIUM BY SEMINAL-VESICLE MESENCHYME

Mesenchymal-epithelial interactions are essential for the development of the male reproductive tract. Tissue recombination experiments have been used to define the characteristics of these interactions. When me senchyme, embryonic connective tissue, is recombined with epithelium f rom another organ an instructive induction may occur in which the deve lopmental fate of the epithelium is altered. Instructive inductions ar e most common when the epithelium that is removed from the mesenchyme and the epithelium that is recombined with the mesenchyme are from the same germ layer. All of the mesenchyme of the male reproductive tract is of mesodermal origin. The epithelia of these organs are derived fr om either the mesodermal Wolffian duct epithelium or the endodermal ur ogenital sinus epithelium. Urogenital sinus mesenchyme can instructive ly induce bladder and urethral epithelium to form prostate (Donjacour, A. A. and Cunha, G. R. (1993) Endocrinol. 132, 2342-2350) and seminal vesicle mesenchyme can instructively induce epithelium from the ductu s deferens and ureter (Cunha, G. R., Young, P., Higgins, S. J. and Coo ke, P. S. (1991) Development 111, 145-158) to form seminal vesicle. To see whether inductive interactions could occur across germ layers in this system, seminal vesicle mesenchyme, normally associated with a me sodermal epithelium, was recombined with epithelium from neonatal or a dult bladder or urethra, which are of endodermal origin. The resulting tissue recombinants were analyzed histologically and by immunocytoche mistry and western blotting with antibodies to prostatic and seminal v esicle secretory proteins. Full prostatic differentiation was observed in tissue recombinants made with seminal vesicle mesenchyme plus eith er adult or neonatal bladder or urethral epithelium. These tissue reco mbinants made dorsolateral but not ventral prostatic secretory protein s. None of them developed into seminal vesicle. To examine whether epi thelial androgen receptors were required for this process, seminal ves icle mesenchyme was recombined with urothelium from mice with the test icular feminization mutation. These mice lack functional androgen rece ptors. While these tissue recombinants grew, no prostatic proteins wer e detected. Seminal vesicle mesenchyme acted as a potent prostatic ind ucer, indicating that similar mesenchymal signals can induce prostatic and seminal vesicle development. Urogenital epithelia of both endoder mal and mesodermal origin appeared to be able to respond to these indu ctive signals produced by the seminal vesicle mesenchyme; however, the ir responses differed depending on their germ layer of origin: mesoder mal epithelium yielding seminal vesicle (Cunha, G. R., Young, P., Higg ins, S. J. and Cooke, P. S. (1991) Development 111, 145-158) and endod ermal epithelium yielding prostate.