LHRH AND THE LOSS OF FERTILITY IN AGING FEMALE RATS

雌性哺乳动物在其发育的早期就停止了生殖周期 寿命 与年龄相关的发情期丧失相关的事件 在实验室大鼠中已经很好地表征了周期性。 而 下丘脑-垂体-卵巢轴所有水平的改变 导致生育能力的丧失，下丘脑似乎是 这一物种的主要缺陷。 与选举有关的变动 下丘脑水平导致LHRH神经分泌的改变， 随后排卵前LH峰消失。 由于发病早， 生殖衰退，老龄雌性大鼠提供了一个重要的模型 用于研究神经内分泌轴中与年龄相关的改变， 严重关切与年龄有关的变化的间接影响， 其他系统。 此外，查明造成这一问题的赤字， 对于老年女性LHRH神经分泌的改变将提供重要的 关于正常生殖周期调节的信息， 目前，还没有得到充分的理解。 而卵巢似乎 作为人类更年期的主要缺陷部位， 有证据表明神经系统也参与其中。 此外， 下丘脑信号可能有助于加速消耗 围月经期的卵泡。 的功能 中年女性的LHRH神经元是建议的重点 问题研究 Fos的免疫细胞化学定位将用于检测 在LH激增期间激活较少LHRH神经元的假设 在老化的动物（实验1）。 原位杂交将用于 检验LHRH基因表达增加的假设 在年轻的动物结合LH激增是显着的 在衰老的动物中减少。 （实验2）。数据比较 这些研究中的年轻和年老的动物应该能够 识别LHRH神经元的特定亚群， 对LH激增至关重要，并在衰老过程中发挥次最大作用 动物 第二系列研究将利用实验性的 操作，以确定赤字的相对贡献， 兴奋性刺激（实验3）或抑制性增强 影响（实验3）与年龄相关的缺陷，在调节 LH分泌。 了解LHRH紊乱的性质 衰老雌性大鼠的神经分泌可能为 不孕症的治疗

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.