CENTRAL NERVOUS SYSTEM REGULATION OF REPRODUCTION

中枢神经系统对生殖的调节

• 批准号: 3310149
• 负责人: CHARLES A BARRACLOUGH
• 金额: $ 16.21万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3310149
• 关键词: brain mapping; catecholamines; electrostimulus; estrogens; follicle stimulating hormone; high performance liquid chromatography; hormone regulation /control mechanism; hypothalamus; luteinizing hormone; neural information processing; neuroendocrine system; ovariectomy; ovulation; pituitary gonadal axis; progesterone; prolactin; radioimmunoassay

the object of the proposed research is to continue our studies on the sites and mechanisms within the central nervous system in which estrogen and progesterone act to affect the preovulatory release of luteinizing hormone and prolactin. To this end we have proposed a series of studies to examine the interplay which exists between these sex steroids and changes in releasability of LHRH from median eminence axon terminals (synaptosomes) using a variety of experimental paradigms. We also propose to examine the duration of occupancy and concentrations of estrogen nuclear and progestin cytosol receptors required to elicit spontaneous LH and PRL surges in long and short term ovariectomized (OVX) rats and the effects of such receptor occupancy on releasability of synaptomsomal LHRH. Coupled with these studies will be an extensive investigation of the critical role that the catechol and indolamine systems exert on the LHRH system to trigger gonadotropin surges. To this end we will examine (a) the input of noradrenergic axons to specific preoptic and hypothalamic regions using electrical activation of the mid and hindbrain noradrenergic cell bodies and/or tegmental tracts; (b) effects of 5-HT on release of LHRH and how 5-HT turnover rates (T/R) change during proestrus and whether they affect norepinephrine (NE) T/R; (c) the effects of estrogen on mid and hindbrain function to activate or inhibit NE T/R in the hypothalamus. Using both estradiol and anti-estrogens we will microimplant these into POA, mid or hindbrain of OVX rats to learn if the LHRH vs NE systems can be independently affected so that LHRH synthesis or NE T/R can be selectively activated or inhibited. Finally, we will study whether puromycin (protein synthesis inhibitor) changes LHRH releasability or NE T/R after E2 treatment. This drug will be discretely placed in preoptic versus brain stem regions. Thus, the studies described in this proposal will examine the importance of the catechol and indol amine systems in triggering LH and PRL release, some of the neuronal and steroid nuclear events involved in this action and how estrogen and progesterone modify the function of both the LHRH and monoamine systems to activate or inhibit LH secretion.

拟议研究的目的是继续我们对这些遗址的研究 以及中枢神经系统内的机制，其中雌激素和 孕酮影响排卵前促黄体激素的释放 和催乳素。 为此，我们提出了一系列研究， 这些性类固醇和性激素变化之间的相互作用 LHRH从正中隆起轴突终末（突触体）的释放能力 使用各种各样的实验范例。 我们亦建议研究 占用时间和雌激素核和孕激素浓度 细胞质受体需要引发自发LH和PRL激增， 和短期卵巢切除（OVX）大鼠的作用和这种受体的影响 占据对突触体LHRH释放能力的影响。 再加上这些 研究将是一个广泛的调查的关键作用， 儿茶酚和吲哚胺系统对LHRH系统施加作用， 促性腺激素激增 为此，我们将检查（a）的输入 去甲肾上腺素能轴突到特定的视前区和下丘脑区域， 中脑和后脑去甲肾上腺素能细胞体的电激活 （B）5-HT对LHRH释放的影响以及如何影响LHRH的释放 5-HT周转率（T/R）在发情前期的变化，以及它们是否影响 去甲肾上腺素（NE）T/R;（c）雌激素对中脑和后脑的影响 在下丘脑中起激活或抑制NE T/R的作用。 同时使用 雌二醇和抗雌激素，我们将这些微植入POA，中期或 OVX大鼠的后脑，以了解LHRH与NE系统是否可以 因此，LHRH合成或NE T/R可以被选择性地 激活或抑制。 最后，我们将研究嘌呤霉素（蛋白质）是否 合成抑制剂）改变E2后LHRH释放能力或NE T/R 治疗 这种药物将被分散放置在视前区和脑内 茎区 因此，本提案中所述的研究将审查 儿茶酚和吲哚胺系统在触发LH和 PRL的释放，一些神经元和类固醇的核事件参与， 这种作用以及雌激素和孕激素如何改变两者的功能， LHRH和单胺系统激活或抑制LH分泌。