The objective of the present project is to use animal models to study the biology of benign prostatic growth. Since animal systems offer a greater degree of flexibility than the human counterpart in manipulation of host conditions, these studies can be conducted to complement findings obtained from studies using human prostates and to widen the scope of the investigation in which reproducible manipulation in host conditions is difficult to accomplish in a human system. The rat prostate will be used extensively in the present proposal, because a great deal of information on the biology of the rat prostate has been available. The canine prostate is also an important model, because dogs are the only species other than man known to develop BPH during aging. Both in vivo and in vitro experiments will be proposed. We will use the in vivo experiments to further characterize the newly recognized prostatic ductal system in which a regional variation in morphological and functional activity of epithelial and stromal cells was observed along the ductal system of the rat prostate. There was also a regional distribution of cell proliferation, differentiation, and degeneration in this ductal system. This regional variation in cellular activities offers an opportunity for us to study the regional variation in the distribution of androgen receptors and growth factors, and to correlate these parameters with cellular growth, differentiation, and degeneration under normal homeostatic conditions and under altered growth conditions. The in vitro experiments mainly involve culture of stromal or epithelial cells of either the rat prostate or the canine prostate. This system will allow us to study the effect of the extracts of growing prostates on the cultured cells in an attempt to identify the natural growth factors in the prostate. It will also allow us to identify the factors associated with the growing prostate that can have an impact on the biological behavior of the cultured cells in terms of proliferation and differentiation. We may use the same system to study the effect of extracts from the regressing prostate in an attempt to identify the factors responsible for prostatic regression. Results of our preliminary study indicated that TGF-beta may be linked to programmed cell death for prostatic epithelial cells. Information generated from these studies should serve as basis for future studies using the human prostate.
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