The long term objectives of the proposed research are the development of a better understanding of cell-cell interactions in the prostate and the influence these interactions have on normal and abnormal (i.e. benign prostatic hyperplasia) prostate physiology. The proposed research tests the hypothesis that stromal cells and epithelial cells in the prostate interact via locally produced paracrine factors and that these interactions are under endocrine control. Specifically the synthesis and secretion of a paracrine factor, termed PModS, which modulates prostatic epithelial cell function and differentiation. The paracrine factor PModS has previously been shown to mediate androgen actions through mesenchymal- epithelial cell interactions in another androgen dependent tissue. The experimental approach consists of four specific aims; l) investigate the production of the paracrine factor PModS by prostatic stromal cells; 2) investigate the actions of the paracrine factor PModS on prostatic epithelial cells; 3) investigate the regulation of PModS production and action in the prostate; 4) investigate the actions of PModS on prostatic morphogenesis and growth. The prostatic stromal cells and epithelial cells utilized in the research will be isolated from rats. Completion of these specific aims will provide a better understanding of prostatic stromal- epithelial cell interactions and the potential general role of the paracrine factor PModS in mediating androgen actions. Information obtained from the proposed research on cell-cell interactions in the prostate is anticipated to provide insight into the control of normal and abnormal prostate physiology. Investigation of this potentially critical regulatory interaction may aid in the future design of treatments for the clinical condition of benign prostatic hyperplasia and prostatic cancer.
