REPRODUCTIVE ENDOCRINOLOGY OF CNS ATRIAL PEPTIDES

该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 肽，称为心房钠尿因子（ANF），发挥强大的 对促性腺激素分泌的影响以及此处详细介绍的研究 将描述这些行为的生理后果， 确定其作用的部位，并描述 这些肽具有确定的神经肽能， 调节下丘脑的儿茶酚胺能系统， 垂体性腺轴 这些信息将进一步推动我们 生殖功能生理方面的知识 并提供了对可能的机制负责的洞察力 病理性内分泌状态 本提案涉及 定义至少一种可能的下丘脑因素 抑制生殖的内分泌。 具体目标是：1） 确定ANF的确切下丘脑作用部位， 促性腺激素分泌通过微量注射肽到特定的 脑部位和测量血浆促性腺激素（促黄体生成 用放射免疫分析法测定阿片类药物的含量; 受体参与心钠素的这种作用，通过使用特定的阿片类药物 拮抗剂阻断其作用，3）研究ANF的能力， 与大脑中的神经递质系统相互作用， 已知通过以下方式控制LH释放激素的分泌： 使用体内和体外操作的组合， 检测ANF阻断儿茶酚胺刺激的LH的能力 释放或改变儿茶酚胺合成和分泌，4） 下丘脑ANF释放的体内变化与 建立LH分泌模式，5）检查 去除当地产生的ANF，通过被动 免疫中和，LH分泌动力学。 除了 表征这些肽在下丘脑中发挥的作用 这些研究将提供 对ANF的其他大脑活动有价值的见解，并将建立 模型系统的神经控制的进一步定义， 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.