NEUROENDOCRINE CONTROL OF SEASONALITY

季节性的神经内分泌控制

• 批准号: 3314878
• 负责人: ROBERT L. GOODMAN
• 金额: $ 12.68万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3314878
• 关键词: bioperiodicity; catecholamines; endorphins; estradiol; estrus; follicle stimulating hormone; hormone regulation /control mechanism; hypothalamic pituitary axis; hypothalamus; immunocytochemistry; in situ hybridization; inhibitor /antagonist; luteinizing hormone; microdialysis; neuroanatomy; neurons; neuropeptides; ovariectomy; ovulation; photobiology; progesterone; prolactin; proopiomelanocortin; seasons; serotonin; sheep; stimulant /agonist; tyrosine 3 monooxygenase

The long term objective of this research is to determine the physiological changes in the hypothalamo-hypophysial unit that are responsible for the reversible suppression of reproductive function. Based on previous work, we have proposed that seasonal alterations of fertility in the ewe result from a photoperiod-induced shift in the neural systems controlling LH secretion. During the breeding season when normal ovarian cycles occur, progesterone appears to inhibit LH pulse frequency via the endogenous opiates (EOP), while estradiol decreases LH pulse amplitude via mechanisms involving both EOP and alpha-adrenergic (NA) neurons. During anestrus, when ovarian cycles cease, these systems are still present, but their effects are superseded by two additional inhibitory neural systems activated by the long-day photoperiod: an estradiol-sensitive catecholaminergic system that accounts for the seasonal variation in estradiol negative feedback and a serotonergic (5HT) system that is responsible for the steroid-independent inhibition of LH secretion in anestrous ewes. The experiments in this proposal will further test this hypothesis by identifying the neural systems involved and begin to explore the neuroendocrine control of these systems. The first specific aim focuses on the catecholaminergic systems activated in anestrus. Previous data suggests that this system involves dopaminergic (DA) cell bodies in the lateral retrochiasmatic area (Al5) that are stimulated by NA input and project to the medial basal hypothalamus (MBH) where they act to inhibit LH release. These experiments will: 1) further test this hypothesis, using radiofrequency lesions in the AI 5, 2) determine where these cell bodies project using anterograde tracing, 3) examine the effects of estradiol and NA tone on release of DA from this system using in vivo microdialysis, and 4) use retrograde tracing techniques to locate the source of the NA input. Experiments in Specific Aim 2 will first use local administration of 5HT agonists and antagonists to determine where in the ovine hypothalamus the steroid-independent inhibition occurs. They will then determine which 5HT perikarya project to this area and if there is a seasonal variation in endogenous release of 5HT in this area. Specific Aim 3 examines the neural systems active in the breeding season. We will first test if estradiol acts via EOP neurons to inhibit GnRH pulse amplitude in the breeding season. The next study uses immunocytochemical and in situ hybridization techniques to determine if different beta-endorphin neurons mediate the negative feedback actions of progesterone and estradiol. A final study examines the possible interactions of EOP and NA neurons in the control of LH pulse amplitude. These studies will provide basic information on the mechanism controlling reproductive function. They will thus broaden our understanding of the physiology (and ultimately the pathology) of normal alterations in reproductive activity, including puberty and the suppression of reproductive function during lactation.

这项研究的长期目标是确定生理 负责的下丘脑 - 高物理单元的变化 可逆抑制生殖功能。 根据以前的工作， 我们提出了母羊结果中生育能力的季节性改变 从光周期诱导的LH神经系统中的移位 分泌。 在繁殖季节正常发生时， 孕酮似乎通过内源性抑制LH脉冲频率 阿片类药物（EOP），而雌二醇通过机制降低LH脉冲振幅 涉及EOP和α-肾上腺素能（NA）神经元。 在Antertus期间， 当卵巢周期停止时，这些系统仍然存在，但是它们 效果被两个额外的抑制性神经系统所取代 长日光周期激活：雌二醇敏感 季节性变化的儿茶酚胺能系统 雌二醇负反馈和血清素能（5HT）系统 负责非依赖类固醇的LH分泌的抑制 生气的母羊。 该提案中的实验将进一步测试 假设通过识别涉及的神经系统并开始探索 这些系统的神经内分泌控制。 第一个特定目标 专注于在Anestrus中激活的儿茶酚胺能系统。 以前的 数据表明，该系统涉及多巴胺能（DA）细胞体 由NA输入刺激和 投影到内侧下丘脑（MBH），以抑制它们 LH释放。 这些实验将：1）进一步检验此假设，使用 AI 5，2）确定这些细胞体的射频病变 使用地线追踪的项目，3）检查雌二醇和 使用体内微透析从该系统释放DA时的Na音调，并且 4）使用逆行跟踪技术定位NA输入的来源。 特定目标2中的实验将首先使用5HT的本地管理 激动剂和拮抗剂确定下丘脑中的何处 发生非依赖性的抑制作用。 然后他们将确定哪个5HT Perikarya项目到该区域，如果有季节性变化 在该区域的5HT内源性释放。 特定目标3检查神经 在繁殖季节活跃的系统。 如果雌二醇，我们将首先测试 通过EOP神经元起作用以抑制繁殖中的GnRH脉冲振幅 季节。 下一项研究使用免疫细胞化学和原位杂交 确定不同β-内啡肽神经元是否介导的技术 孕酮和雌二醇的负反馈作用。 最终研究 检查了EOP和Na神经元在控制中的可能相互作用 LH脉冲振幅。 这些研究将提供有关 控制生殖功能的机制。因此，他们将扩大我们的 理解正常的生理（以及最终的病理学） 生殖活动的改变，包括青春期和抑制 泌乳过程中生殖功能。