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）对神经细胞膜的反馈调节作用 垂体LH分泌与性附属器官功能的维持 在男性中。 SBP是睾酮的高亲和力结合剂， 雄性循环雄激素，并存在于许多哺乳动物的血浆中 这种蛋白质被认为影响包括人类在内的所有物种。 雄激素的作用和代谢。 两种动物模型将用于 这些研究：1）阉割的成年雄性大鼠--一种没有或 非常少的内源性SBP，因此允许独立的 通过控制慢性输注，操纵血浆SBP和 雄性小棕蝠（Myotis lucifugus） lucifugus-一种与类固醇具有高亲和力SBP的哺乳动物 结合特征与灵长类动物相似， 循环SBP的季节性变化至少为20倍 同意。 利用大鼠模型，研究将在 在稳态和动态两种情况下， 模式，以确定SBP和性类固醇对 前列腺和精囊以及下丘脑和垂体 LH分泌的调节。 由于血浆SBP的季节性变化较大， 在小棕蝙蝠可以诱导在实验室中， 完整雄性，该动物将用于研究变化的影响 在内源性SBP的产生对雄激素刺激的性 副腺 此外，生殖周期的独特性 雄性小棕蝠的数量（即，性别的季节性增长 当血浆睾酮稳定时的副腺重量，或 下降）可以让我们阐明的基本方面， 明显的雄激素非依赖性现象，如良性增生的 前列腺 在这些患者中，SBP对雄激素作用的影响比较 这两个物种应该提供了关于性别相互作用的有价值的信息 激素和SBP在男性生殖功能调节中的作用。

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.