Our long term objective is to prevent human BPH (benign prostatic hyperplasia) or to improve the clinical course of individuals suffering from it. The present application was proposed with the assumption that the canine prostate is an acceptable model for studying the pathogenesis of human BPH and with the hypothesis that systemic, primarily hormonal, factors other than androgen are required in the canine BPH pathogenesis. The present application postulates that two sources of these critical non-androgenic humoral factors warrant consideration: PITUITARY and TESTIS. The testis, besides secreting testosterone, is known to produce a large variety of substances. Among them are estrogen, androgen binding protein, transferrin, inhibin, Mullerian inhibiting substance, etc. The cells responsible for the production of these substances are Sertoli cells. Results of our initial experiments summarized in this report indicate a role for the testes in the maintenance of BPH in old dogs and experimental induction of BPH in young dogs. The serum and prostatic tissue hormone levels noted in these experiments support the concept that the systemic factor(s) responsible for this role is a non-androgenic secretory product. The pituitary secretes hormones having direct effects on the testis which, in turn, stimulates prostatic growth and function. In addition, these hormones and others (e.g. prolactin) may act synergistically with androgen to promote prostatic growth and possibly to induce and promote BPH development. Therefore, the objectives for the present proposal are two-fold. First, we propose to conduct both in vivo and in vitro experiments in an attempt to demonstrate a direct effect of pituitary secretions on the canine prostate. Second, in vitro experiments will be conducted to study the effects of Sertoli cell secretions on the canine prostate. Specifically, the following experiments will be conducted: (1) Hypophysectomy and castration in experimental dogs and evaluate the effect of estrogen-androgen synergism on canine prostate, (2) pituitary grafting under the renal capsule and study the castration-induced regression and androgen-stimulated growth of the canine prostate, (3) establish organ culture system for the canine prostate and to study the direct effect of various non- androgenic substances, and (4) to establish tissue culture systems of the canine Sertoli cells and to use the Sertoli cell spent media for qualitative protein analysis (two-dimensional electrophoresis) and to cultivate the canine prostate.
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