A program is proposed to continue comprehensive study of human and canine prostatic hyperplasia (BPH) to further our understanding of the etiology, prevention and treatment of this most prevalent disease. Animal Studies: Our previous studies indicate that the canine is an appropriate model to study the basic principles applicable to human BPH. We have observed that BPH occurs in the canine at a very early age, at which time the prostate is marked to have an increased sensitivity in its response to androgens. It is proposed to study the role of hormones and aging in determining this sensitivity and to establish whether the administration of regulated amounts of androgen and estrogen can prevent the onset of this disease. Attention will be given to the role of testicular function and estrogens, as etiological factors in BPH. It appears that BPH may be the result of a stem cell disorder and methods are proposed to identify the various cellular components of the prostate and to determine their function and role in cell renewal and cell turnover. The role of the extracellular matrix in abnormal prostate growth will be studied in relation to the content and distribution of glycosaminoglycans, collagens, and glycoproteins. In vitro systems will be designed to study the function of the extracellular matrix in relation to aging, prostatic function, and growth. Studies are proposed to elucidate changes in the compartmentalization and quantities of androgen, estrogen, and progesterone receptors in relation to development of BPH. Neurotransmitter receptors in the prostate will be characterized and localized to identify approached for neuropharcacological control of prostatic function and BPH. Stereological analysis will be made of the prostatae and testes to privide quantitataive analysis of changes occurring in these glands in relation to aging and BPH. Human Studies: We will continue to correlate the above findings in the canine with human tissue derived from normal and BPH prostates. It is proposed to determine whether the progression of established BPH is correlated with alterations in gonadotropin and sex steroid horomone levels. A clinical trial is proposed to determine whether supression of testicular function induced by treatment with synthetic GnRH agonist will induce regression of established BPH.
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