The studies described in this proposal are designed to investigate the effects of sex hormone binding protein (SBP) on the feedback regulation of pituitary LH secretion and the maintenance of sex accessory organ function in the male. SBP is a high-affinity binder of testosterone, the major circulating androgen in males, and is found in the plasma of many mammalian species including man. This protein has been postulated to influence both the action and metabolism of androgens. Two animal models will be used for these studies: 1) the castrated adult male rat - an animal which has no or very little endogenous SBP and will therefore permit the independent manipulation, by controlled chronic infusions, of both plasma SBP and testosterone, and 2) the adult male little brown bat, Myotis lucifugus lucifugus - a mammal which possesses a high - affinity SBP with steroid binding characteristics similar to those of primates and which also wxhibits at least a 20-fold seasonal variation in circulating SBP consentrations. Utilizing the rat model, studies will be conducted in which testosterone will be administered in both steady-state and dynamic patterns to determine the action/interactions of SBP and sex-steroids on the prostate and seminal vesicles and on the hypothalamic and pituitary regulation of LH secretion. since the large seasonal changes in plasma SBP in little brown bats can be induced in the laboratory in both castrated and intact males, this animal will be used to study the effects of variations in endogenous SBP production on the androgenid stimulation of the sex accessory glands. In addition, the unique nature of the reproductive cycle of the male little brown bat (i.e., large seasonal increases in sex accessory gland weights at a time when plasma testosterone is stable or declining) may allow us to elucidate basic aspects of the apparently-androgen-independent phenomena such as benign hyperplasia of the prostate. A comparison of the effects of SBP on androgen action in these two species should provide valuable information on the interaction of sex steroids and SBP in the regulation of male reproductive function.
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