LHRH AND THE LOSS OF FERTILITY IN AGING FEMALE RATS

下丘脑-垂体-卵巢轴的改变是 明显存在于雌性哺乳动物生命的早期。在实验室里 大鼠，正常的发情周期在8-12个月龄时停止，但 该物种的平均寿命约为24个月。这个 导致生殖衰老的缺陷的原发部位 在雌性大鼠身上似乎是下丘脑。很多人对此很感兴趣 尤其是黄体生成素的变化 释放激素(LHRH)神经分泌。了解 导致下丘脑改变的本质 从两个方面来看，该物种的生殖衰退是重要的 透视。首先，因为生殖衰退发生得太早了 在人的一生中，导致衰老的特定事件 可以在不考虑间接影响的情况下进行研究 其他系统中与年龄相关的变化的影响。第二, 因为LHRH神经分泌受损被认为是 许多人在生殖功能的丧失中扮演着重要角色， 模型变得特别有趣。许多问题都围绕着 促性腺激素释放激素分泌的神经调节与老年女性 RAT在系统内表现出扰动。因此， 下丘脑发生的改变的特征 中年(MA)女性将提供关于 幼龄骑行动物LHRH神经分泌的调节。 而卵巢似乎是营养不良的主要部位。 人类更年期，下丘脑水平的改变 肯定会导致卵巢功能丧失。这个 本提案中的一系列实验将检验 LHRH系统、LHRH神经分泌模式和特异性 与LHRH控制有关的神经化学因素 老年女性的神经分泌。第一个实验将 结合活体(推拉灌流和脉搏波测量 促黄体生成素释放)和体外(灌流)方法直接和 间接评估老年女性的LHRH神经分泌。 在第二个实验中将采用脑室内输液 在试图改变已知影响LHRH的特定系统中 释放，以确定这些兴奋性或 抑制作用可能与生殖衰老有关。 将在第三个月采用免疫细胞化学方法 做实验。LHRH系统和其他几个系统 与LHRH释放的神经调节有关的是 在发情前期的下午进行检查，以确定 在MA和年轻女性中存在的差异，并可能 导致与年龄相关的黄体生成素分泌的改变。

Alterations in the hypothalamic-pituitary-ovarian axis are apparent early in the lifespan of female mammals. In laboratory rats, regular estrous cycles cease at 8-12 months of age, yet the average lifespan of the species is approximately 24 months. The primary site of the deficitis that lead to reproductive senescence in female rats appears to be the hypothalamus. Much interest has centered, in particular, on alterations in luteinizing hormone releasing hormone (LHRH) neurosecretion. Understanding the nature of the hypothalamic changes that contribute to reproductive decline in the species is important from two perspectives. First, because reproductive decline occurs so early in the lifespan, the specific events that contribute to senescence of a system can be studied without major concern for indirect influences from age-related alterations in other systems. Second, because impairment of LHRH neurosecretion is considered by many to play a major role in the loss of reproductive function, the model becomes particularly interesting. Many questions surround the neural modulation of LHRH secretion, and the aging female rat exhibits perturbations within the system. Therefore, characterization of the hypothalamic alterations that occur in middle aged (MA) females will yield important information about the modulation of LHRH neurosecretion in young cycling animals. Whereas the ovary appears to be the primary site of deficit in human menopausae, alterations at the hypothalamic level certainly could contribute to the loss of ovarian function. The series of experiments in the present proposal will examine the LHRH system, patterns of LHRH neurosecretion, and specific neurochemical factors implicated in the control of LHRH neurosecretion in aging females. The first experiment will combine in vivo (push pull perfusion and measurement of pulsatile LH release) and in vitro (superfusion) methods to both directly and indirectly assess LHRH neurosecretion in aging females. Intraventricular infusions will be employed in the 2nd experiment in an attempt to alter specific systems known to influence LHRH release in order to determine which of these excitatory or inhibitory influences might contribute to reproductive senescence. An immunocytochemical approach will be taken in a 3rd experiment. The LHRH system and several other sytems implicated in the neural modulation of LHRH release will be examined on the afternoon of proestrus in order to identify differences that exist in MA and young females and could contribute to the age-related alterations in LH secretion.