SEX STEROID BINDING PROTEIN AND ANDROGEN ACTION

本提案中描述的研究旨在调查 性激素结合蛋白(SBP)在中枢神经系统反馈调节中的作用 垂体促黄体生成素分泌与性辅助器官功能的维持性 在男性身上。SBP是一种高亲和力的睾酮结合剂，是主要的 雄性体内的循环雄激素，存在于许多哺乳动物的血浆中 包括人类在内的物种。这种蛋白质被认为会影响这两种蛋白质 雄激素的作用和代谢。两个动物模型将用于 这些研究：1)去势的成年雄性大鼠-一种没有或 内源性SBP很小，因此将允许独立的 通过控制慢性输液控制血浆SBP和 睾丸激素，以及2)成年雄性小棕蝠，Myotis Lucifugus 萤火虫-一种具有与类固醇高亲和力的SBP的哺乳动物 与灵长类动物相似的结合特征，也 循环SBP至少有20倍的季节性变化 请多关照。利用老鼠模型，研究将在 哪种睾丸素将在稳态和动态状态下使用 确定SBP和性激素对人的影响/相互作用的模式 前列腺和精囊以及下丘脑和垂体腺 黄体生成素分泌的调节。由于血浆SBP的季节性变化很大 在实验室里，小棕色蝙蝠可以被诱导去势和 完整的雄性，这只动物将被用来研究变异的影响 内源性SBP的产生对性激素刺激的影响 附腺。此外，生殖周期的独特性质 雄性小棕色蝙蝠(即，性季节性的大幅增加 在血浆睾酮稳定或正常时的附腺重量 拒绝)可能使我们能够阐明 明显的雄激素非依赖性现象，如卵巢良性增生症 前列腺。SBP对上述人群雄激素作用的比较 两个物种应该提供有关性别相互作用的有价值的信息 激素和SBP在调节男性生殖功能中的作用。

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.