LHRH AND THE LOSS OF FERTILITY IN AGING FEMALE RATS

雌性哺乳动物在早期就不再表现出生殖周期 寿命。发情中与年龄相关的丢失的相关事件 在实验室大鼠身上，循环性已经得到了很好的表征。鉴于 下丘脑-垂体-卵巢轴的所有水平的改变 导致生育能力丧失，下丘脑似乎是 这一物种的主要缺陷点。与年龄相关的变化 下丘脑水平导致LHRH神经分泌的改变 随后失去排卵前的促黄体生成素高峰。由于发病较早， 生殖功能减退，为老龄雌性大鼠提供了重要的模型 用于研究与年龄相关的神经内分泌轴的改变 严重关注与年龄相关的变化的间接影响 其他系统。此外，确定应负责任的赤字 对于老年女性LHRH神经分泌的改变将提供重要的 关于调节正常生殖周期的信息，在 目前，仍然没有得到充分的理解。而卵巢看起来 是人类更年期缺陷的主要部位，有几行 有证据表明，神经也参与其中。此外，更改 下丘脑信号可能参与了脑电活动的加速耗竭 围绝经期的卵泡。的功能 中年女性的LHRH神经元是建议的重点 学习。Fos的免疫细胞化学定位将用于检测 促黄体生成素释放激素神经元在促黄体生成素激动期被激活的假设 在老年动物中(实验1)。将使用原位杂交技术 检验LHRH基因表达增加观察到的假设 在幼年动物中，伴随着黄体生成素激增的是显著的 在衰老的动物中会减少。(实验2)。数据的比较来自 这些研究中的年轻和老年动物应该能够 LHRH神经元特定亚群的鉴定 对黄体生成素激增和衰老时功能低于最大值至关重要 动物。第二系列研究将利用实验 确定赤字相对贡献率的操作 兴奋性刺激(实验3)或增强抑制性 调节对年龄相关性缺陷的影响(实验3) 促黄体生成素的分泌。了解LHRH中扰动的性质 衰老雌性大鼠的神经分泌可能为 不孕不育的治疗。

Female mammals cease exhibiting reproductive cycles early in their lifespan. The events surrounding the aged-related loss in estrous cyclicity have been well characterized in laboratory rats. Whereas alterations at all levels of the hypothalamic-pituitary-ovarian axis contribute to the loss of fertility, the hypothalamus appears to be the major site of deficit in this species. Aged-related changes at the hypothalamic level result in alterations in LHRH neurosecretion and the subsequent loss of the preovulatory LH surge. Due to the early onset of reproductive decline, the aging female rat provides an important model for the study of age-related alteration in a neuroendocrine axis without serious concern about indirect effects from age related alterations in other systems. In addition, identification of the deficits responsible for altered LHRH neurosecretion in aging females will provide important information about the regulation of normal reproductive cycles which, at present, remains inadequately understood. Whereas the ovary appears to be the primary site of deficit in human menopause, several lines of evidence suggest neural involvement as well. Moreover, alteration in hypothalamic signals might contribute to the accelerated depletion of ovarian follicles during the perimenopausal period. The function of LHRH neurons in middle-aged females is the focus of the proposed studies. Immunocytochemical localization of Fos will be used to test the hypothesis that fewer LHRH neurons are activated during an LH surge in aging animals (Experiment 1). In situ hybridization will be used to test the hypothesis that the increase in LHRH gene expression observed in young animals in conjunction with the LH surge are significantly diminished in aging animals. (Experiment 2). Comparisons of data from the young and aging animals in these studies should enable identification of specific subgroups of LHRH neurons that are both essential for the LH surge and functioning submaximally in aging animals. A second series of studies will utilize experimental manipulations to determine the relative contributions of deficits in excitatory stimulation (Experiment 3) or enhancement of inhibitory influences (Experiment 3) to the age-related deficit in the regulation of LH secretion. Understanding the nature of the disturbance in LHRH neurosecretion in aging female rats may provide valuable insights for the treatment of infertility.