NEUROENDOCRINE REGULATION OF THE ESTROUS CYCLE

不孕不育、人口过剩和生殖障碍是主要的 社会面临的问题。本提案的重点是整合 人体的三大通讯系统--内分泌、 中枢神经和免疫系统-以及这如何影响 雌性的排卵周期。内分泌和神经的重要性 协调周期中的事件和协调的系统 生殖过程与外部环境，长期以来一直 被认可了。然而，直到最近，免疫系统才开始发挥作用 站到最前面来。免疫系统阐述了一连串的神经系统 和体液信号，当受到炎性刺激和侵袭时 外来生物对身体的伤害。通过机制不完全 要知道，这些免疫信号会强烈地抑制生殖。这个 这项研究的主要目标是确定免疫挑战如何 影响神经内分泌轴，抑制卵巢周期。这个 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和观察到的变化 标准化免疫挑战后的神经内分泌活动 (内毒素)。通过这种方式，对生殖至关重要的过程 镇压将被精准地定位。具体目标1阐明了这种影响 在发情周期中的免疫挑战。这将通过以下方式实现 评估内毒素对激素事件进展的影响 周期的卵泡和黄体阶段，并通过评估 卵巢类固醇对免疫后神经内分泌反应的影响 挑战。特定目标2阐述了一种免疫 激发可抑制促性腺激素释放激素和促黄体生成素的搏动性分泌。这包括 针对下丘脑水平的研究(分泌物 GnRH进入垂体门静脉血)和垂体腺水平 (对GnRH的反应性)。具体目标3侧重于 免疫刺激对促性腺激素释放激素和促黄体生成素分泌高峰的影响。这包括如何 免疫挑战影响雌激素受体神经元的激活 在下丘脑，浪涌诱导信号的转导 GnRH神经元网络，以及GnRH和GnRH的实际电涌过程 促黄体生成素释放。这项研究采用了多种方法，包括 监测下丘脑、脑下垂体的激素分泌 和卵巢以及下丘脑系统的免疫细胞化学分析 已知对繁殖至关重要。与健康相关的 这项工作将提供一个深入的综合分析如何 免疫挑战、传染病和炎症性疾病、身体损伤 和创伤，以及各种有害刺激导致生殖 失败了。

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.