NEURAL INFLUENCE ON HYPOPHYSEAL-GONADAL FUNCTION

神经对垂体-性腺功能的影响

• 批准号: 3313792
• 负责人: HAROLD G SPIES
• 金额: $ 25.55万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-01 至 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3313792
• 关键词: antiadrenergic agents; blood chemistry; brain mapping; catecholamines; cerebral dominance; cholecystokinin; corticotropin releasing factor; dialysis; drug administration routes; eating; endorphins; estradiol; estrus; follicle stimulating hormone; gonadotropin releasing factor; gonadotropins; hormone inhibitor; hormone receptor; hormone regulation /control mechanism; hypophysectomy; hypothalamic pituitary axis; hypothalamus; inhibin; laboratory rabbit; luteinizing hormone; menstrual cycle; naloxone; neural information processing; neuroendocrine system; neuropeptide Y; neuropeptide receptor; neuropeptides; norepinephrine; ovariectomy; passive immunization; perfusion; phentolamine; pituitary gonadal axis; progesterone; prolactin; prolactin releasing /inhibiting factor; radioimmunoassay; radiotracer; secretion; sex behavior; stereotaxic techniques; substance P

Rhythmic bursts of gonadotropin-releasing hormone (GnRH) from hypothalamic neurons are essential for initiation and maintenance of secretion of the gonadotropins. The frequency and amplitude of these neural and pituitary events are regulated, in turn, by circulating levels of estradiol-17 beta (E2) and progesterone (P). One of these ovarian steroids, E2, inhibits luteinizing hormone (LH) release, whereas it enhances GnRH release; the second steroid (P) slows pulsatile LH release, in part, by increasing central opioid inhibition of GnRH secretion. The identify of other neuropeptides and catecholamines and their mode of actions and interactions of GnRH secretion in the ovulatory process and the normal menstrual cycle remain unclear. We propose to measure the patterns of GnRH in push-pull perfusion (PPP) samples from the hypothalamus and to compare these GnRH patterns with those of peripheral gonadotropins, E2, and P during the menstrual cycle in rhesus macaques and in the periovulatory period in rabbits. We will examine the roles of selected neuropeptides (neuropeptide Y, endorphins, corticotropin-releasing factor, and substance P) and that of norepinephrine in control of GnRH release by one or more of three methods: ( 1) measure their endogenous release rates in PPP samples, (2) infuse the test compound intrahypothalamically and measure changes in GnRH release, and (3) give specific antagonists or antibodies to a peptide and record these effects on endocrine and post-coital behavioral parameters. We will then study the influence of E2, P, and cortisol on the release of selected peptides and catecholamines in PPP samples and relate these findings to those on GnRH release. We propose also to measure GnRH release after intrahypothalamic infusion of pituitary hormones and inhibin and after unilateral ovariectomy for direct evidence on shortloop feedback and on hypothalamic laterality in feedback signaling. To explore these hypothalamo- hypophyseal interactions, we will use specific radioimmunoassays for peptides and steroids and a radioenzymatic assay for the catecholamines. Blood and/or PPP samples will be collected during superfusion of hypothalamic tissues (in vitro) and hypothalamic PPP in freely-moving females (in vivo). These findings will provide insight into how the hypothalamus influences the normal reproductive process, and hence may be useful in treating certain causes of infertility, anorexia nervosa, and obesity.

人促性腺激素释放激素(GnRH)的节律性爆发 下丘脑神经元对于启动和维持是必不可少的。 促性腺激素的分泌。频率和幅度 这些神经和垂体事件中的一部分，反过来又由 血清雌二醇-17β(E_2)和孕酮(P)水平。 其中一种卵巢类固醇，E2，抑制黄体生成素 (Lh)释放，而它促进促性腺激素释放激素释放；第二 类固醇(P)减缓黄体生成素的脉动性释放，部分是通过增加 中枢阿片类药物对促性腺激素释放激素分泌的抑制。其他人身份识别 神经肽和儿茶酚胺及其作用方式和 促性腺激素释放激素在排卵过程中的相互作用 正常月经周期尚不清楚。我们建议测量 推拉灌流(PPP)标本中促性腺激素释放激素(GnRH)的变化 并将这些GnRH模式与那些 月经周期外周促性腺激素、E_2和P的变化 在恒河猴和兔的排卵期。我们 将研究选定的神经肽(神经肽Y、 内啡肽、促肾上腺皮质激素释放因子和P物质)和 去甲肾上腺素对一种或多种促性腺激素释放的控制 三种方法之一：(1)测定其内源释放率 PPP样品，(2)下丘脑内注入试验化合物 和测量GnRH释放的变化，以及(3)给出具体的 多肽的拮抗剂或抗体，并记录这些影响 内分泌和性交后行为参数。到时候我们会的 雌二醇、孕酮和皮质醇对大鼠肾皮质激素释放的影响 PPP样品中选择的多肽和儿茶酚胺及其相关 这些发现对那些GnRH发布的人来说。我们还提议 下丘脑注射促性腺激素释放激素的测定 单侧卵巢切除后垂体激素和抑制素的变化 关于短路反馈和下丘脑的直接证据 反馈信号的片面性。去探索这些下丘脑- 垂体腺的相互作用，我们将使用特异性放射免疫分析 对于多肽和类固醇，以及对 儿茶酚胺。将采集血液和/或PPP样本 在下丘脑组织灌流期间(体外)和 自由活动女性的下丘脑PPP(活体)。这些 这些发现将为深入了解下丘脑如何影响 正常的生殖过程，因此在 治疗某些原因的不孕不育、神经性厌食症和 肥胖。