Our long term goal is to understand the role of tissue degradation in abnormal growth of the human prostate, namely, benign prostatic hyperplasia and prostatic carcinoma. The present proposal deals with the study of basic biology of prostatic regression in the rat. Since the rat prostate involutes at an accelerated, yet predictable, rate upon castration in the host, many biological parameters, currently unclear to us, can be identified and characterized as events associated with prostatic regression. These events are likely pre-programmed and are likely destined to cellular destruction. It should be pointed out that it is not the objective of the present proposal to study the mechanism of action of testosterone and prolactin in the rat prostate. If results of these studies are able to contribute to our knowledge in hormone action, it is not done so by our design. The following three areas are proposed: (1) Study of protein synthesis in regressing prostate: Results of our previous studies have continuously supported the concept that prostatic regression involves an active metabolic process. We propose that, during prostatic regression, a few protein species are actively synthesized to facilitate the regressive process. With the technique of two-dimensional electrophoresis, it is possible for us to compare different protein species that are synthesized by the normal prostate and by the regressing prostate. (2) Characterization of degradative enzymes in regressing prostate: Earlier results indicate that activities of degradative enzymes play an important role in tissue regression. In addition to the study of synthesis and degradation, we propose to study cellular distribution of various degradative enzymes. We will first characterize cathepsin D and prostatic acid phosphatase, since we have developed the antibody against the former and identified the latter in the rat prostate. As other important proteins are identified, they will be added to the list of our investigation. (3) Study of the effect of prolactin on degradative enzymes: Results of our previous studies have indicated that prolactin is not likely to participate in the synthetic activities in the regressing prostate. We propose that the effect of prolactin in causing a delay in prostatic regression lies in its ability to alter the activities of intracellular degradative enzymes. We plan to study the effect of prolactin on cell death, on pattern of protein synthesis and on distribution of degradative enzymes in the rat prostate. The fate of prolactin in the regressing prostate will also be studied.
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