REPRODUCTIVE ENDOCRINOLOGY OF CNS ATRIAL PEPTIDES

这项提案的目标是定义一类新的 生殖内分泌学中的下丘脑肽。这些 多肽，称为心钠素(ANF)，发挥强大的 促性腺激素分泌的影响及相关研究 将表征这些行为的生理后果， 确定他们的行动地点，并描述 这些具有已建立的神经肽和 调节下丘脑的儿茶酚胺能系统- 垂体-性腺轴。这一信息将进一步推动我们的 生殖功能的生理方面的知识 并提供对以下可能的机制的洞察 病理性内分泌状态。这项提案涉及 定义至少一种下丘脑因子，它可以 抑制生殖内分泌。具体目标是：1) 确定心钠素抑制作用的确切下丘脑部位 特异性注射促性腺激素多肽的分泌 脑部位和血浆促性腺激素的测定(黄体化 激素-黄体生成素)放射免疫法，2)阿片类药物的鉴定 受体通过使用特异性阿片剂参与心钠素的这一作用 拮抗剂阻断其作用，3)研究ANF的能力 与大脑内的神经递质系统相互作用 已知可通过以下方式控制促黄体生成素释放激素的分泌 使用体内和体外操作的组合，该操作 检测心钠素对儿茶酚胺刺激的促黄体生成素的阻断作用 释放或改变儿茶酚胺的合成和分泌，4) 下丘脑心钠素释放的活体变化与 已建立的促黄体生成素分泌模式，以及5)检查 被动法去除本地生产的硝酸铵 免疫中和，对促黄体生成素分泌动力学的影响。除了……之外 表征这些多肽在下丘脑中的作用 控制报告性内分泌学，这些研究将提供 对ANF的其他大脑活动的有价值的见解，并将建立 神经控制的进一步定义的模型系统 生殖功能。

The goal of this proposal is to define the role of a new class of hypothalamic peptides in reproductive endocrinology. These peptides, called atrial natriuretic factors (ANF), exert potent effects on gonadotropin secretion and the studies detailed here will characterize the physiologic consequences of these actions, identify the site of their action and describe the interaction of these peptides with established neuropeptidergic and catecholaminergic systems which regulate the hypothalamo- pituitary-gonadal axis. This information will further our knowledge of the physiological aspects of reproductive function and provide insight into the possible mechanisms responsible for pathologic endocrine states. This proposal deals with the definition of at least one of the hypothalamic factors which can inhibit the endocrinology of reproduction. Specific aims are to: 1) identify the exact hypothalamic site of action of ANF to inhibit gonadotropin secretion by microinjecting the peptide into specific brain sites and measuring plasma gonadotropins (luteinizing hormone-LH) by radioimmunoassay, 2) identify the class of opiate receptor involved in this action of ANF by using specific opiate antagonists to block its action, 3) investigate the ability of ANF to interact with neurotransmitter systems within the brain which are known to control the secretion of LH-releasing hormone, by using a combination of in vivo and in vitro manipulations which examine the ability of ANF to block catecholamine stimulated LH release or to alter catecholamine synthesis and secretion, 4) correlate in vivo changes in hypothalamic release of ANF with established patterns of LH secretion, and 5) examine the effect of removal of locally produced ANF, by passive immunoneutralization, on LH secretory dynamics. In addition to characterizing the role these peptides play in the hypothalamic control of reporductive endocrinology, these studies will provide valuable insight into other brain actions of ANF and will establish model systems for the further definition of the neural control of reproductive function.