BRAIN MONOAMINES AND LUTEINIZING HORMONE SECRETION

脑单胺和黄体生成素的分泌

• 批准号: 2655101
• 负责人: WILLIAM R CROWLEY
• 金额: $ 9.63万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-12-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2655101
• 关键词: dopamine; electron microscopy; endogenous opioid; endorphins; enkephalins; gonadotropin releasing factor; hormone receptor; hormone regulation /control mechanism; hyperprolactinemia; hypothalamus; immunocytochemistry; in situ hybridization; laboratory rat; lactation; light microscopy; luteinizing hormone; neuroendocrine system; neuropeptide Y; neurotensin; pituitary gland; prolactin; second messengers; secretion; tissue /cell culture

The overall objective of this research program has been to identify and characterize the actions of hormone (LH) and prolactin (PRL) from the anterior pituitary gland in response to the central neurotransmitter and neuropeptide systems that regulate the secretion of luteinizing physiological stimuli. Neuropeptide Y (NPY) functions in this system as an amplifier of the signals provided by the adrenergic transmitters to stimulate LH-releasing hormone (LHRH) secretion and also augments the signal provided to the gonadotrophe by LHRH. In this application, we propose to extend this research into a new physiological context, following the recent demonstrations that the synthesis of NPY in the medial-basal hypothalamus is up-regulated in lactation, and that at least part of this is attributable to a novel expression of the peptide in the tuberoinfundibular dopamine (TIDA) neurons. At present, neither the biological significance of, nor the physiological signals that evoke, this state-specific altered expression of NPY are known, and the proposed studies are designed to address these two questions. Because the ADA system is the major neuroendocrine PRL-inhibiting system, we hypothesize that the increased NPY present in the medial basal hypothalamus may affect PRL secretion from the anterior pituitary gland by modulating the action of DA on the lactotrophes and/or the release of DA from the hypothalamus. Second, we will examine whether the suppression of gonadotropin secretion during lactation that is produced by the suckling stimulus and elevated PRL is mediated by the increased NPY via an interaction with endogenous opioids. As the third main objective, we will test whether PRL and/or the suckling stimulus is the physiological signal that leads to increased NPY expression in the medial-basal hypothalamus during lactation. The first Specific Aim contains in vitro studies that will investigate the effects of NPY and NPY-DA interactions on second messenger systems and PRL secretion in cultured anterior pituitary cells. The second Specific Aim will use in vitro and in vivo approaches to examine whether NPY modulates the release of DA from the median eminence of lactating rats. In vivo studies of the third Specific Aim will determine the roles of DA and NPY in generating the episodic pattern of PRL secretion during lactation and measure the pattern of NPY and DA release during nursing. The fourth Specific Aim will investigate whether an NPY-endogenous opioid interaction mediates the inhibition of gonadotropin secretion during lactation by testing the in vivo effects of NPY and NPY antagonists, and by examining NPY-opioid interaction, in episodic LH secretion and LHRH receptor regulation in lactating rats. These studies will also investigate in vitro effects of NPY on LHRH and Beta-endorphin release from medial-basal hypothalamus of lactating rats. The fifth Specific Aim will evaluate whether the suckling stimulus and/or a central action of PRL is the physiological signal responsible for enhanced NPY expression in the medial basal hypothalamus during lactation. These studies will test the effects of producing hyperprolactinemia in non-lactating rats and of suppression of PRL release in lactating rats on a) NPY immunoreactivity in the medial basal hypothalamus (by RIA), b) NPY immunoreactivity and innervation pattern in TIDA and non-TIDA neurons (by light and EM immunocytochemistry), and c) preproNPY mRNA levels in TIDA and non-TIDA neurons (by in situ hybridization).

这项研究计划的总体目标是确定和 描述激素（LH）和催乳素（PRL）的作用， 垂体前叶对中枢神经递质的反应， 调节促黄体激素分泌的神经肽系统 生理刺激神经肽Y（NPY）在该系统中的功能是 肾上腺素能递质提供的信号放大器， 刺激LH释放激素（LHRH）分泌，也增加 由LHRH提供给促性腺激素细胞的信号。在本申请中，我们 建议将这项研究扩展到一个新的生理背景， 在最近的证明中， 内侧基底下丘脑在哺乳期上调，至少 这部分归因于该肽在大肠杆菌中的新表达。 结节漏斗多巴胺（TIDA）神经元。目前， 生物学意义，也不是引起的生理信号， 这种状态特异性改变的NPY表达是已知的， 研究旨在解决这两个问题。因为助理检察官 系统是主要的神经内分泌PRL抑制系统，我们假设 下丘脑内侧基底部的NPY增加可能 影响垂体前叶分泌PRL的调节 DA对催乳素的作用和/或DA从催乳素中的释放 下丘脑第二，我们将研究是否压制 哺乳期哺乳动物产生的促性腺激素分泌 刺激和升高的PRL是通过增加NPY介导的， 与内源性阿片类药物的相互作用。作为第三个主要目标， 测试PRL和/或吮吸刺激是否是生理信号 导致下丘脑内侧-基底区NPY表达增加 在哺乳期。第一个特定目标包含体外研究， 将研究NPY和NPY-DA相互作用对第二次 信使系统和催乳素分泌。 第二个具体目标将使用体外和体内方法， 检查NPY是否调节DA从正中隆起的释放 哺乳期的老鼠第三个特定目标的体内研究将 确定DA和NPY在产生发作性模式中的作用， 泌乳期PRL分泌及NPY、DA含量测定 在护理期间释放。第四个具体目标将调查是否 NPY-内源性阿片样物质相互作用介导对 通过测试体内效应的泌乳期促性腺激素分泌 的NPY和NPY拮抗剂，并通过检查NPY-阿片样物质的相互作用， 哺乳期大鼠的LH分泌和LHRH受体调节。 这些研究还将研究NPY对LHRH的体外作用， 哺乳期大鼠下丘脑内侧-基底节β-内啡肽的释放。 第五项具体目标将评估哺乳刺激和/或 催乳素的一个中心作用是负责 下丘脑内侧基底核NPY表达增强 哺乳期这些研究将测试生产的影响， 非哺乳期大鼠高催乳素血症及催乳素抑制 a）内侧基底膜中的NPY免疫反应性 B）NPY免疫反应性和神经支配模式 在TIDA和非TIDA神经元中（通过光和EM免疫细胞化学），和 c）TIDA和非TIDA神经元中的preproNPY mRNA水平（通过原位测定） 杂交）。