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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

基本信息

批准号：
6168800
负责人：
SANDRA J. LEGAN
金额：
$ 22.06万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-07-16 至 2003-06-30
项目状态：
已结题

项目摘要

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.

这项提议的长期目标是阐明变化的作用女性年龄相关性生殖功能障碍患者的下丘脑功能。在幼年大鼠，去甲肾上腺素(NE)介导阳性和阴性雌二醇对下丘脑黄体生成素的反馈作用促黄体生成素(LHRH)，从而促黄体生成素(LH) 分泌物。在那些仍然表现出常规行为的中年大鼠中发情周期，对正反馈和负反馈的反应雌二醇的作用减弱，昼夜节律被打乱，导致基础促黄体生成素分泌和促黄体生成素激增的变化。它还有待于确定这些与年龄相关的促黄体生成素分泌变化，可能是生殖功能障碍和衰老的先兆，是由 LHRH神经元附近NE释放的变化。因此这项建议将侧重于NE在与年龄相关的减少中的作用雌二醇对黄体生成素分泌的负反馈和正反馈作用。第一个特定的AIM将检验基础NE释放的假设去卵巢(OVX+E)大鼠斜角带内随着年龄的增长而增加，早期和晚期释放增加与幼年大鼠的促黄体生成素激增相关的激素被减弱或取消中年大鼠。第二个特定的目标将检验以下假设以幼鼠体内典型的去甲肾上腺素释放模式替代中年大鼠对角带恢复运动的时间和幅度促黄体生成素水平与幼年大鼠相当。第三个特定的AIM将测试假设去甲肾上腺素在对角带的早期释放增加年轻的OVX+E大鼠是促黄体生成素激增的启动和/或定时信号。这个第四个特定的AIM将检验NE晚期增加的假设幼年OVX+E大鼠斜角带释放高峰控制左旋波突波的大小。建议数研究将确定LHRH细胞体区域的去甲肾上腺素释放在清醒、自由活动的动物体内进行高密度微透析加压液相色谱。这些研究对我们的对中枢神经系统调节机制的理解生殖衰老，因为它们将决定去甲肾上腺素在雌二醇对黄体生成素分泌的反馈作用及其作用生殖衰老中的这些机制。