Neuroendocrine Control of Seasonality

季节性的神经内分泌控制

• 批准号: 6788045
• 负责人: ROBERT L. GOODMAN
• 金额: $ 24.83万
• 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 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6788045
• 关键词: bioperiodicity; estradiol; estrogen receptors; estrogens; estrus; female; hormone regulation /control mechanism; hypothalamus; immunocytochemistry; in situ hybridization; luteinizing hormone; melatonin; neural plasticity; neuroanatomy; neuroendocrine system; neurophysiology; neuroregulation; neurotransmitters; ovariectomy; ovulation; seasons; sex cycle; sheep

DESCRIPTION: (provided by applicant) The long-term goal of this research is to understand the structural and functional changes in the hypothalamus that are responsible for the reversible suppression of ovarian function, such as occurs prior to puberty. It has been recognized for over 40 years that increases in response to estradiol (E2) negative feedback play a major role in producing these periods of infertility (e.g., the gonadostat theory of puberty), but the underlying changes in hypothalamo-pituitary function remain largely unknown. Using seasonal breeding as a model, we have identified a neural circuit (the vmPOA-RCh system) that plays a key role in alterations in E2 negative feedback in the ewe. This circuitry mediates E2 inhibition of gonadotropin-releasing hormone (GnRH) pulse frequency and is activated during periods of anovulation (anestrus) and inactivated during periods of fertility (breeding season). The first specific aim will better characterize this circuit by determining the phenotype of estrogen-responsive elements in the vmPOA and RCh and evaluating the role of ER in mediating the actions of E2. The second specific aim will test three alternate explanations for the activation of this system in anestrus: an increase in estrogen receptors, an increase in key neurotransmitter levels, or an increase in synaptic contacts within the circuit. The third specific aim will begin to determine the mechanisms by which external factors control the activity of this circuit. There is now evidence that another hypothalamic area, the premammillary region (PMR) controls changes in responsiveness to E2 negative feedback. The experiments in Specific Aim 3, we will examine the anatomical and functional connections between this area and the vmPOA-RCh system and test the hypothesis that it is critical for changes in response to E2 negative feedback. These questions will be addressed using a combination of anatomical, molecular and physiological approaches that include immunocytochemical analysis (at the light and electron microscopic levels), in situ hybridization, tract-tracing, local administration of drugs and hormones to different hypothalamic areas, and the production of small hypothalamic lesions. The results of these studies will provide fundamental information on the control of reproductive function and on neural plasticity in the adult brain that may be relevant to both physiological and pathological suppression of ovarian function.

描述：（由申请人提供）这项研究的长期目标是 了解下丘脑的结构和功能变化 负责可逆抑制卵巢功能，例如 青春期之前。它被认可了40多年，增加了 对雌二醇（E2）负面反馈的反应在产生中起主要作用 这些不育时期（例如，青春期的性腺理论），但 下丘脑 - 垂体功能的潜在变化在很大程度上未知。 使用季节性育种作为模型，我们已经确定了神经回路（ VMPOA-RCH系统）在E2负反馈中起关键作用 在母羊中。该电路介导了促性腺激素释放的E2抑制 激素（GNRH）脉冲频率，并在电卵形期间被激活 （抗激源）并在生育时期（繁殖季节）灭活。这 第一个特定目的将通过确定该电路来更好地表征该电路 VMPOA和RCH中雌激素响应元件的表型和评估 ER在介导E2的作用中的作用。第二个特定目标将 测试三个替代解释，以激活该系统 Anestrus：雌激素受体的增加，钥匙的增加 神经递质水平或突触接触的增加 电路。第三个特定目标将开始确定 外部因素控制该电路的活动。现在有证据 在另一个下丘脑区域，前机会区域（PMR）控制着变化 对E2负面反馈的响应。特定目标3中的实验， 我们将研究该区域和该领域之间的解剖和功能连接 VMPOA-RCH系统并检验了以下假设：它对于变化至关重要 对E2负反馈的响应。这些问题将使用 解剖学，分子和生理方法的结合，包括 免疫细胞化学分析（在光和电子显微镜水平上），在 原位杂交，道追踪，药物和激素的局部给药 到不同下丘脑区域，以及小小的下丘脑的产生 病变。这些研究的结果将提供有关的基本信息 成人生殖功能和神经可塑性的控制 可能与生理和病理抑制相关的大脑 卵巢功能。