NEURAL CONTROL OF LUTEINIZING HORMONE SECRETION IN AGING

衰老过程中黄体生成素分泌的神经控制

• 批准号: 2732589
• 负责人: SANDRA J. LEGAN
• 金额: $ 20.41万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-16 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2732589
• 关键词: aging; alpha antiadrenergic agent; circadian rhythms; estradiol; estrus; female; gonadotropin releasing factor; hormone regulation /control mechanism; hypothalamic pituitary axis; hypothalamus; juvenile animal; laboratory rat; luteinizing hormone; mature animal; microdialysis; neural transmission; neuroregulation; neurotransmitter transport; norepinephrine; ovariectomy; prazosin; radioimmunoassay; secretion

The long-term goal of this proposal is to elucidate the role of changing hypothalamic function in age-related reproductive dysfunction in females. In young rats, norepinephrine (NE) mediates the positive and negative feedback actions of estradiol that govern hypothalamic luteinizing hormone releasing hormone (LHRH), and thereby pituitary luteinizing hormone (LH) secretion. In those middle-aged rats that are still exhibiting regular estrous cycles, the responses to both the positive and negative feedback actions of estradiol are diminished, and circadian rhythms are disrupted, leading to changes in basal LH secretion and LH surges. It remains to be determined whether these age-related changes in LH secretion, that may be harbingers of reproductive dysfunction and senescence, are caused by alterations in NE release in the vicinity of the LHRH neurons. Therefore this proposal will focus on the role of NE in the age-related decrease in the negative and positive feedback actions of estradiol on LH secretion. The FIRST SPECIFIC AIM will test the hypothesis that the basal NE release in the diagonal band of estradiol-treated ovariectomized (OVX+E) rats increases with age and that the early and late increases in release associated with the LH surge in young rats are attenuated or abolished in middle-aged rats. The SECOND SPECIFIC AIM will test the hypothesis that replacement with a pattern of NE release typical of young rats into the diagonal band of middle-aged rats restores the timing and magnitude of the LH surge to those of young rats. The THIRD SPECIFIC AIM will test the hypothesis that the early increase in NE release in the diagonal band of young OVX+E rats is the priming and/or timing signal for the LH surge. The FOURTH SPECIFIC AIM will test the hypothesis that the late increase in NE release in the diagonal band of young OVX+E rats, which occurs at the peak of the LH surge, controls the magnitude of the LH surge. The proposed studies will determine NE release in the region of the LHRH cells bodies in conscious, freely-moving animals by in vivo microdialysis with high pressure liquid chromatography. These studies are critical to our understanding of central nervous system mechanisms that mediate reproductive senescence because they will determine the role of NE in the feedback actions of estradiol on LH secretion and will determine the role of these mechanisms in reproductive aging.

这项提案的长期目标是阐明改变 下丘脑功能与女性年龄相关性生殖功能障碍 在年轻大鼠中，去甲肾上腺素（NE）介导了正性和负性的 雌二醇对下丘脑促黄体激素的反馈作用 释放激素（LHRH），从而垂体促黄体生成激素（LH） 分泌物 在那些仍然表现出规律性的中年大鼠中， 发情周期，对积极和消极反馈的反应 雌二醇的作用减弱，昼夜节律被打乱， 导致基础LH分泌和LH激增的变化。 还有待 确定是否这些年龄相关的LH分泌的变化，这可能是 生殖功能障碍和衰老的先兆，是由 LHRH神经元附近NE释放的改变。 因此 这项建议将集中在NE在年龄相关的减少中的作用， 雌二醇对LH分泌的负反馈和正反馈作用。 第一个特定目标将检验基础NE释放 雌二醇处理的卵巢切除（OVX+E）大鼠的斜角带 随着年龄的增长，早期和晚期的释放增加， 与年轻大鼠LH激增相关的免疫抑制作用减弱或消失， 中年老鼠 第二个具体目标将检验以下假设： 替换为NE释放的模式，典型的年轻大鼠进入 中年大鼠的斜角带恢复的时间和幅度的 LH激增到年轻大鼠的水平。 第三个具体目标将测试 假设早期增加NE释放的对角线带， 年轻OVX+E大鼠是LH峰的启动和/或定时信号。的 第四个具体目标将检验NE的晚期增加 在年轻OVX+E大鼠的斜角带中释放， 控制LH峰的大小。 拟议 研究将确定NE在LHRH细胞体区域的释放 在有意识的，自由移动的动物体内微透析与高 高压液相色谱法 这些研究对我们的 了解中枢神经系统的机制， 生殖衰老，因为它们将决定NE的作用， 雌二醇对LH分泌的反馈作用，并将决定作用 这些机制在生殖衰老中的作用。