NEUROENDOCRINE REGULATION OF THE ESTROUS CYCLE

不育、人口过剩和生殖失调是主要问题 社会面临的问题。 本提案侧重于整合 体内的三大通讯系统--内分泌， 中枢神经和免疫系统-以及这如何影响 女性的排卵周期 内分泌和神经的重要性 系统在编排周期的事件，并在协调 生殖过程与外部环境的关系， 认可. 然而，直到最近，免疫系统的作用 走到最前面。免疫系统会产生一连串的神经 和体液信号时，受到炎症刺激和入侵 被外来的有机体破坏 通过不充分的机制 这些免疫信号强烈地抑制生殖。的 这项研究的主要目的是确定免疫挑战如何 影响神经内分泌轴，抑制卵巢周期。 的 一般的方法是整合现有的生理学知识， 绵羊发情周期的基础， 标准化免疫激发后的神经内分泌活性 （内毒素）。 通过这种方式，对生殖至关重要的过程 将被压制。 具体目标1阐明了影响 发情周期的免疫挑战。 为实现这些目标将 评估内毒素对激素事件进展的影响 的卵泡和黄体阶段的周期，并通过评估 卵巢激素对免疫反应神经内分泌的影响 挑战. 具体目标2解决免疫机制， 激发抑制GnRH和LH的脉冲式分泌。 这包括 针对下丘脑水平（分泌 促性腺激素释放激素进入垂体门静脉血）和垂体水平 （对GnRH的反应）。具体目标3侧重于 促性腺激素释放激素（GnRH）和促黄体生成激素（LH）分泌激增免疫攻击。 这包括如何 免疫刺激影响雌二醇受体神经元的激活 在下丘脑，浪涌诱导信号的转导， GnRH神经元网络，以及GnRH的实际激增过程， LH释放 该研究采用了多种方法，包括 监测下丘脑、脑垂体、 以及下丘脑系统的免疫细胞化学分析 对繁殖至关重要 与健康相关的 这项工作是，它将提供一个深入的综合分析，如何 免疫挑战、感染性和炎症性疾病、身体损伤 和创伤，以及各种有害刺激导致生殖 失败

Infertility, overpopulation and reproductive disorders are major problems facing Society. This proposal focuses on integration of the three great communication systems in the body - the endocrine, the central nervous and the immune systems - and how this impacts the ovulatory cycle of females. The importance of the endocrine and nervous systems in orchestrating the events of the cycle, and in coordinating reproductive processes with the external environment, has long been recognized. Only recently, however, has the role of the immune system come to the forefront. The immune system elaborates a cascade of neural and humoral signals when challenged by inflammatory stimuli and invasion of the body by foreign organisms. Through mechanisms not fully understood, these immune signals powerfully inhibit reproduction. The broad objective of this research is to determine how an immune challenge impacts the neuroendocrine axis to inhibit the ovarian cycle. The general approach is to integrate current knowledge of the physiologic basis for the estrous cycle of sheep with observed changes in neuroendocrine activity following a standardized immune challenge (endotoxin). In this manner, processes critical to reproductive suppression will be pinpointed. Specific Aim 1 elucidates the influence of an immune challenge on the estrous cycle. This will be achieved by assessing the effects endotoxin on progression of the hormonal events of the follicular and luteal phases of the cycle, and by assessing the influence of ovarian steroids on neuroendocrine responses to an immune challenge. Specific Aim 2 addresses mechanisms whereby an immune challenge inhibits pulsatile secretion of GnRH and LH. This includes investigations directed at both the hypothalamic level (secretion of GnRH into pituitary portal blood) and the pituitary level (responsiveness to GnRH). Specific Aim 3 focuses on the impact of an immune challenge on surge secretion of GnRH and LH. This includes how an immune challenge impacts activation of estradiol receptive neurons in the hypothalamus, the transduction of the surge inducing signal to the GnRH neuronal network, and the actual surge processes of GnRH and LH release. The research incorporates a variety of approaches including monitoring secretion of hormones from the hypothalamus, the pituitary and the ovary, and immunocytochemical analysis of hypothalamic systems known to be crucial to reproduction. The health-related relevance of this work is that it will provide an in depth integrated analysis of how immune challenges, infectious and inflammatory disease, physical injury and trauma, and a variety of noxious stimuli lead to reproductive failure.