Our long term goal is to study the role of tissue degradation in abnormal growth of human prostate, namely, benign prostatic hyperplasia and prostatic carcinoma. Tissue growth or regression results from an imbalance of opposing processes of continuing synthesis and degradation. However, the degradative process, in sharp contrast with the detail understanding of the synthetic process, is poorly understood. The present proposal deals with the study of basic biology of prostatic regression in the rat. Since the rat prostate involutes at an accelerated rate following castration of the host, many parameters can be defined and characterized as events associated with tissue regression. Our previous studies confirmed our original hypotheses that prostatic regression involved activation of degradative enzymes. During the last grant period, we were able to study: (1) the basic pattern of prostatic regression, (2) the modification of this basic pattern of regression by various agents, (3) the role of ribonuclease (RNase) and cathepsin D in prostatic regression, and (4) the effect of prolactin and estrogen on prostatic regression. To pursue further the mechanism of prostatic regression, we propose to conduct studies in following four areas: (1) Enzyme Studies: Rates of synthesis and degradation of RNase and cathepsin D in the prostate will be determined at different stages of tissue regression. Immunological approaches and pulse-labelling methods will be employed. (2) Steroid Metabolism: The pattern of testosterone metabolism to dihydrotestosterone and androstane-3alpha, 17beta-diol in prostatic tissue will be studied by in vivo labelling with radioactive testosterone. Effects of prolactin and estradiol will be investigated. (3) Metabolic Events: At different stages of prostatic regression, collagen contents, water imbibition, mRNA synthesis in the tissue and responsiveness to testosterone or estradiol by the prostatic tissue will be determined. We will study all 3 lobes of the prostate. (4) Morphological Studies: histological and ultrastructural studies will be carried out to substantiate the biochemical observations. Emphasis will be placed on acini structure, collagen fibers and lysosomal particles in the regressing and regressed prostates.
Showing the most recent 10 out of 16 publications
