Our long term goal is to prevent benign prostatic hyperplasia (BPH) or improve the clinical course of individuals suffering form it by an acceptable modification of testicular secretion. The goal of the present study is to utilize the dog model to provide indirect evidence to evaluate the hypothesis that a non-androgenic accessory sex gland stimulating substance or substances which play a major role in the development and/or maintenance of BPH are secreted by the testes. Radiation of the testes does not effect testicular testosterone secretion, but may reduce the secretion of the postulated non-androgenic accessory sex gland stimulating substance particularly if it is secreted by cells other than leydig cells. This reduction will objectively alter the development and maintenance of BPH. Our preliminary results are encouraging and strongly support the concept that the testis secretes a substance other than testosterone which plays a significant role in maintenance and progression of BPH in dogs. The effect and presumably the secretion of this testicular substance can be altered significantly by radiation. This is an important concept which, if confirmed, would significantly alter the approach to studies that have prevention or medical management of BPH as a goal. However, our preliminary results must be confirmed under different experimental conditions. 4 Experiments are proposed: 1) Effect of Radiation on the Testes on Established Spontaneous BPH in the Dog. 2) Effect of Radiation of the Testes on Prevention of Spontaneous BPH. 3) Effect of Radiation of the Testes on testosterone induced BPH. 4) Effect of Radiation of the testes on dihydrotestosterone-induced BPH. In addition to gravimetric and histologic changes previously observed, we propose to conduct biochemical analysis on the prostatic tissues collected from experimental animals. These analyse include determination of DNA and protein contents; acid phosphatase activities and tissue accummulation of dihydrotestosterone. We think this is the 1st attempt to study the direct effect of testicular irradiation on pathologic prostatic growth systematically. Proposed studies are designed to confirm and extend preliminary observations to provide further evidence to support the existance of a non-testosterone, testicular substance which promotes BPH development. The probability that this substance plays a critical role in the initial development of BPH is high, but experimental studies to support this probability are just being initiated and are part of this proposed study.
