The emphasis of this proposal will be to test the hypothesis that human benign prostatic hyperplasia (BPH) is associated with an alteration in the epithelial-stromal interaction in which the stroma re-expresses embryonic-like inductive influences and, thus, stimulates the neoformation of glandular acini in adjacent epithelial cells. The efficacy of hormonal agonists and/or antagonists in promoting or inhibiting stromal inductive activities during the neoformation of glandular elements will be explored. Finally, pilot studies of selected biochemical parameters pertaining to the mechanisms of this inductive process will be examined. To accomplish these goals the follwoing experimental conditions will be utilized: (1) To test whether BPH stroma is inductive, recombinants consisting of stroma from normal or hyperplastic prostates (BPH) and recombinants will be subjected to morphological, histochemical and steroid autoradiographic procedures for the presence and/or development of androgen receptor activity. (2) To determine whether epithelium from BPH or normal human prostate is capable of responding to inductive cues from stroma, recombinants will be prepared with isolated epithelium from human prostates and embryonic mouse urogenital sinus mesenchyme (a prostatic inductor). (3) To investigate the hormonal regulation of stromal influence upon epithelial morphogenesis, experiments will be designed to test the hormonal requirements for morphogenetic induction. Furthermore, sensitive biochemical methods of assessing epithelial hyperplasia and the ontogeny of cellular proteins (2-dimensional gel electrophoresis) will be developed.