Benign prostatic hypertrophy involves abnormal proliferation of both the epithelium and fibromuscular stroma. Considering that the retinoids are capable of modulating the function of cells of mesenchymal origin and can also prevent or even reverse abnormal growths of epithelial cells in a variety of systems including the prostate, retinoids may have major relevance to the etiology and pharmacological management of benign prostatic hypertrophy. This proposal is devoted to developing a basic understanding of the importance of endogenous retinoids to normal and abnormal androgen and estrogen-induced growths of the male accessory sex organ epithelium and muscle. It is hypothesized that androgens regulate the intracellular retinoid environment in male accessory sex organs. In turn, retinoids may play and essential role in supporting the normal actions of androgen on epithelium and muscle cell proliferation and differentiation. Estrogens will induce abnormalities in muscle cell differentiation and proliferation which retinoids will theoretically inhibit by competing for the estrogen-receptor interaction. The ability of androgen to block estrogen-induced abnormal growth is hypothesized to be mediated by effects of endogenous retinoids on the estrogen receptor. This research will utilize the guinea pig seminal vesicle instead of prostate glands since the organ can be surgically separated into pure epithelim and muscle which provides for the unique ability to perform quantitative analyses on each tissue type. Experiments will initially involve expanding the understanding of the normal and abnormal actions and interactions of androgen and estrogen on muscle and epithelial cell differentiation using 2 dimensional gel electrophoretic analyses of both soluble protein composition and protein phosphorylation. Secondly, there will be a definition of the relationship of vitamin A deficiency and supplementation with vitamin A, retinoic acid and N(4-hydroxyphenyl) retinamide to androgen and estrogen action and interaction on muscle and epithelial cell proliferation and differentiation. Thirdly, in search of the potential mechanism of steroid hormone-retinoid interaction, the retinoid-induced changes in the intracellular fate of androgen and estrogen in the epithelim and muscle will be quantified along with the influence of androgen and estrogen on retinoid levels and retinoic acid binding proteins.
