BRAIN MONOAMINES AND LUTEINIZING HORMONE SECRETION

脑单胺和黄体生成素的分泌

• 批准号: 3312273
• 负责人: WILLIAM R CROWLEY
• 金额: $ 13.34万
• 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 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3312273
• 关键词: GABA receptor; brain metabolism; epinephrine; estradiol; gamma aminobutyrate; genital secretion; high performance liquid chromatography; hormone inhibitor; hormone regulation /control mechanism; hypothalamus; laboratory rat; luteinizing hormone; messenger RNA; neurochemistry; neuroendocrine system; neurohormones; neurons; neuropeptide Y; neuropeptides; neurotransmitter metabolism; norepinephrine; pituitary gonadal axis; progesterone; prolactin; radioimmunoassay; radiotracer; sex hormones; sympathetic nervous system; thin layer chromatography; tritium

The overall objective of this research project is to investigate the neurochemical mechanisms by which the ovarian hormones, estradiol (E2) and progesterone (P), exert their feedback controls over the secretion of luteinizing hormone (LH) from the anterior pituitary gland, and the overall hypothesis under investigations that the stimulatory and inhibitory effects of the ovarian hormones on the secretion of LH are mediated by changes in the activity of monoaminergic and peptidergic systems that regulate, directly or indirectly, the neurosecretion of LH-releasing hormone (LHRH) from the median eminence. This renewal application focusses on the interplay between the adrenergic neurotransmitters, norepinephrine (NE) and epinephrine (EPI), and neuropeptides, including endogenous opioids and neuropeptide Y, in mediating aspects of ovarian hormone positive feedback on LHRH and LH secretion in adult female rats, and secondly, on the effects exerted by gonadal hormones during the early neonatal period that influence the responsiveness of these neurotransmitter and neuropeptide systems to ovarian hormones in adulthood. The specific aims of this proposal are first, to further investigate the interactions between the adrenergic neurotransmitters and NPY and between NPY and LHRH in mediating ovarian hormone positive feedback. These experiments will examine the involvement of adrenergic and NPY systems in inducing the changes in LHRH concentrations in the median eminence that precede the ovarian hormone- induced LH surge and in mediating the stimulatory effect of P on LHRH release in vitro. Additional studies will investigate the action of opioid and GABA systems to regulate NPY and adrenergic transmission controlling LHRH release, and will further characterize the mechanisms and the physiological significance of the facilitation by NPY of LHRH-induced LH release from anterior pituitary cells. The second specific aim is to examine whether ovarian hormones, and adrenergic, opioid and/or GABA systems influence the levels of NPY precursor mRNA in the medial basal hypothalamus. The third set of studies will more completely characterize the changes in adrenergic-peptidergic control over LHRH neurosecretion in rats defeminized by early exposure to E2, specifically by testing whether the neurochemical antecedents of the LH surge induced in normal females by ovarian hormones or antagonists at opioid or GABA receptors (i.e., accumulation of LHRH and NPY, activation of NE/EPI turnover) occur in feminized animals, but fail to occur in defeminized animals, of both sexes. The fourth specific aim is to investigate whether defeminization by neonatal exposure to E2 affects the development of the inhibitory EOP and GABAergic controls over the release of adrenergic transmitters and LHRH, and whether neonatal exposure to E2 with respect to ovarian hormone positive feedback mechanisms.

这项研究项目的总体目标是调查 卵巢激素、雌二醇(E_2)和 黄体酮(P)，发挥其反馈控制的分泌 促黄体生成素(黄体生成素)来自垂体前叶，总体上 在调查中的假说是刺激和抑制效应 卵巢激素对促黄体生成素分泌的影响是通过 调节单胺和多肽能系统的活动， 直接或间接的促黄体生成素释放激素(LHRH)神经分泌 从中间隆起。此续订申请侧重于 肾上腺素能神经递质与去甲肾上腺素(NE)的相互作用 和肾上腺素，以及神经肽，包括内源性阿片和 神经肽Y在卵巢激素正反馈中的中介作用 对成年雌性大鼠促性腺激素释放激素和促黄体生成素分泌的影响 在新生儿早期性腺激素施加的影响 这些神经递质和神经肽系统对 成年期的卵巢激素。这项提议的具体目的是 首先，为了进一步研究肾上腺素能神经元之间的相互作用 神经递质与神经肽Y及其与促性腺激素释放激素的关系 荷尔蒙正反馈。这些实验将检验这种牵连 肾上腺素能系统和神经肽Y系统在诱导LHRH变化中的作用 卵巢激素之前的正中隆起的浓度- 促黄体生成素释放峰及P对LHRH的刺激作用 体外释放。其他研究将调查阿片类药物的作用 和GABA系统调节NPY和肾上腺素能传递控制 LHRH的释放，并将进一步表征其机制和 NPY易化LHRH诱导的促黄体生成素的生理意义 从脑垂体前叶细胞释放。第二个具体目标是 检查卵巢激素、肾上腺素能、阿片和/或GABA 不同系统对内侧基底区NPY前体mRNA水平的影响 下丘脑。第三组研究将更全面地描述 肾上腺素能-肽能调控LHRH神经分泌的变化 早期暴露于雌二醇组的大鼠，特别是通过测试 黄体生成素诱发正常女性黄体生成素峰的神经化学先兆 卵巢激素或阿片或GABA受体拮抗剂(即， LHRH和NPY积聚，NE/EPI周转激活) 雌性化的动物，但不会出现在去雌化的动物中，无论性别。 第四个具体目标是调查去女性化是否通过 新生儿暴露于E2影响抑制性EOP的发展和 GABA能控制肾上腺素能递质和LHRH的释放， 以及新生儿暴露于雌二醇是否与卵巢激素有关 正反馈机制。