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，更具体地了解 调节促性腺激素的分泌和生理作用， 促性腺激素释放激素（GnRH）导致排卵。最近有人 确定，在发情周期的卵泡期， 羊，有一个深刻的变化，在脉动模式的GnRH 分泌，然后是大量和长期的排卵前GnRH激增， 远远超过LH激增。这一建议的前提是， 卵泡期GnRH分泌模式的变化是 在很大程度上是由雌二醇分泌的变化引起的， 排卵前卵泡的发育，以及由此产生的GnRH激增， 排卵前事件序列表达的关键信号。 有四个具体目标，每一个都针对以下一个问题 问题： 雌二醇是否通过引起促性腺激素释放激素水平的进行性变化来诱导GnRH激增 GnRH神经分泌系统的输出，导致从 从严格的脉冲到持续释放 雌二醇信号的性质是什么，导致进行性 GnRH释放的变化？ 需要多少大规模和长期的GnRH激增才能诱导 排卵前LH激增，如果有的话，所有GnRH的功能是什么？ 在LH高峰期之后分泌 雌二醇是否能增强GnRH基因的表达并刺激合成， GnRH从细胞体到终端的神经元运输过程中激增？ 这些问题将使用各种实验设计来解决 和方法，包括：直接监测GnRH分泌， 垂体门静脉血;特异性雌二醇信号的模式传递; 给予GnRH拮抗剂以阻断以下生物学作用 内源性促性腺激素释放激素;促性腺激素释放激素mRNA原位杂交;测定 及其前体在下丘脑组织中的表达; 和放射免疫测定来监测各种激素的循环模式。 该项目对健康相关问题的重要性在于， 直接与控制排卵有关，因此与生育有关 调控拟议的研究将提供一个描述 促性腺激素释放激素的分泌动力学导致排卵， 这些模式，在一个从未达到的水平。获得的信息 将增强卵巢正常生理学的基础知识， 周期;这应该导致新的方法来操纵生育率。

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.