NEUROENDOCRINE REGULATION OF THE ESTROUS CYCLE

这项研究的长期目标是了解神经内分泌。 卵巢周期的调节，更具体地说要了解 促性腺激素的分泌和生理作用的调节- 促排卵激素(GnRH)。它最近一直在 确定在发情周期的卵泡期 绵羊促性腺激素释放激素的搏动模式发生了深刻的变化 分泌之后是一个巨大的和持续的排卵前GnRH激增 远远超过了左撇子的激增。这项建议是在以下前提下提出的 卵泡期促性腺激素释放激素分泌模式的变化 在很大程度上是由雌激素分泌的变化引起的 发育中的排卵前卵泡，由此产生的GnRH激增是 这是排卵前事件序列表达的关键信号。 有四个具体目标，每个目标都是为了解决以下问题之一 问题： 雌二醇是否通过引起促性腺激素释放激素释放激素的渐进性变化来诱导促性腺激素释放激素的激增 GnRH神经分泌系统的输出，导致从 严格脉动到连续释放？ 雌激素信号的本质是什么，导致进行性 GnRH版本的变化？ 需要多少大规模和持续的GnRH激增才能诱导 排卵前促黄体生成素激增以及所有促性腺激素释放激素的功能是什么？ 分泌超过黄体生成素高峰的时间？ 雌二醇是否促进促性腺激素释放激素基因表达并刺激合成和 突变期促性腺激素释放激素从细胞体到终末的神经元运输？ 这些问题将通过各种实验设计来解决。 方法包括：直接监测促性腺激素释放激素分泌到 脑垂体门静脉血；特定雌二醇信号的模式化传递； 给予促性腺激素释放激素拮抗剂以阻断 内源性GnRH；GnRH mRNA的原位杂交；GnRH的测定 及其前体在下丘脑组织中监测GnRH基因的表达； 以及放射免疫分析，以监测各种激素的循环模式。 这个项目对健康相关问题的意义在于它 直接与排卵的控制有关，因此与生育有关。 监管。拟议的研究将提供关于 促性腺激素释放激素促排卵的分泌动态及其调节 这些模式，达到了前所未有的水平。所获得的信息 将增强卵巢正常生理的基本知识 周期；这应该导致操纵生育率的新方法。

The long-term goal of this research is to understand the neuroendocrine regulation of the ovarian cycle, more specifically to understand regulation of the secretion and the physiological actions of gonadotropin- releasing hormone (GnRH) leading up to ovulation. It has recently been determined that, during the follicular phase of the estrous cycle of sheep, there is a profound change in the pulsatile pattern of GnRH secretion followed by a large and prolonged preovulatory GnRH surge that far outlasts the LH surge. This proposal is developed on the premise that changes in the pattern of GnRH secretion during the follicular phase are caused, in large measure, by changes in the secretion of estradiol from the developing preovulatory follicle, and that the resulting GnRH surge is a crucial signal for expression of the preovulatory sequence of events. There are four specific aims, each to address one of the following questions: Does estradiol induce the GnRH surge by causing a progressive change in output of the GnRH neurosecretory system, leading to a switch from strictly pulsatile to continuous release? What is the nature of the estradiol signal that causes the progressive changes in GnRH release? How much of the massive and prolonged GnRH surge is needed to induce the preovulatory LH surge and what, if any, is the function of all the GnRH secreted beyond the time of the LH peak? Does estradiol enhance GnRH-gene expression and stimulate synthesis and neuronal transport of GnRH from cell bodies to terminals during the surge? These questions will be addressed using a variety of experimental designs and approaches including: direct monitoring of GnRH secretion into pituitary portal blood; patterned delivery of specific estradiol signals; administration of a GnRH antagonist to block the biological actions of endogenous GnRH; in situ hybridization for GnRH mRNA; measurement of GnRH and its precursor in hypothalamic tissue to monitor GnRH gene expression; and radioimmunoassays to monitor circulating patterns of various hormones. The significance of this project to health-related issues is that it pertains directly to the control of ovulation and, thus, to fertility regulation. The proposed research will provide a description of the secretory dynamics of GnRH leading to ovulation, and the regulation of those patterns, at a level never before achieved. The information gained will enhance basic knowledge of the normal physiology of the ovarian cycle; this should lead to new approaches to manipulating fertility.