LHRH AND THE LOSS OF FERTILITY IN AGING FEMALES

雌性大鼠的生殖能力下降首先表现为 在发情前期LH激增的模式中， 周期性LH激增 衰老中LH分泌模式的年龄相关变化 据推测，女性最终是由于LHRH的释放改变， 垂体门脉系统 目前信息很少 然而，关于LHRH释放在老龄雌性大鼠。 的 本文提出的一系列实验将表征LHRH神经分泌 在老化的雌性大鼠中，他们将确定1） LHRH释放的模式可以完全归因于年龄相关的变化， LHRH神经元的传入输入或2）LHRH内的改变 神经元本身也会导致生育能力的丧失。 在实验1中， 推拉灌注将用于表征LHRH的模式 中年和年轻女性在发情前期或 卵巢切除术和类固醇治疗后 如果更改 LHRH释放的脉动模式的幅度或频率是 在老化动物中观察到的，将尝试逆转这些 肾上腺素能激动剂给药引起的变化。 在实验2中， 来自正中隆起中的孤立神经末梢的神经分泌物将被 在非特异性（K+）和特异性（PGE 2，NE） 刺激. 这种方法将允许检查可能与年龄有关的 下丘脑储存的LHRH的释放能力的变化，除了其他 年龄相关的变化，例如，传入输入，这也可能起作用， 改变体内LHRH释放。 在实验3中，LHRH的反应 中年和年轻女性的系统将被观察如下： 电化学刺激（100 μ A/60秒）内侧视前区。 实验3的结果将确定LHRH系统是否在 衰老的雌性大鼠保持对刺激做出反应的能力， 对合成和释放的需求增加。 最后，免疫细胞化学 技术将在实验4中使用，以研究解剖 儿茶酚胺能和LHRH系统之间相互作用的基础。 LHRH与儿茶酚胺合成酶的共定位 酪氨酸羟化酶和多巴胺β羟化酶将用于检查 LHRH系统的传入输入可能与年龄有关。

Reproductive decline in female rats is characterized first by alterations in the pattern of the LH surge on proestrus and finally by complete absence of cyclic LH surges. Age related changes in LH secretory patterns in aging females are presumed to result ultimately from altered release of LHRH into the pituitary portal system. Very little information is currently available, however, regarding LHRH release in aging female rats. The series of experiments proposed here will characterize LHRH neurosecretion in aging female rats and they will determine whether 1) alterations in the patterns of LHRH release can be attributed solely to age related changes in the afferent input to the LHRH neurons or 2) alterations within the LHRH neurons themselves contribute to the loss of fertility. In experiment 1, push-pull perfusion will be utilized to characterize the pattern of LHRH secretion in middle-aged and young females on the day of proestrus or following ovariectomy and steroid administration. If alterations in amplitude or frequency of the pulsatile pattern of LHRH release are observed in the aging animals, attempts will be made to reverse these changes by administration of adrenergic agonists. In experiment 2, LHRH neurosecretion from isolated nerve terminals in the median eminence will be examined in vitro following non-specific (K+) and specific (PGE2, NE) stimulation. This approach will allow examination of possible age related changes in releasability of hypothalamic stores of LHRH apart from other age related changes, for example, in afferent input, that might also act to alter LHRH release in vivo. In experiment 3, the response of the LHRH system of middle-aged and young females will be observed following electrochemical stimulation (100MuA/60 sec) of the medial preoptic area. The results of experiment 3 will determine whether the LHRH system in the aging female rat maintains the capacity to respond to a stimulus causing increased demand for synthesis and release. Finally, immunocytochemical techniques will be employed in experiment 4 to investigate the anatomical basis for interaction between the catecholaminergic and LHRH systems. Co-localization of LHRH with the catecholamine synthesizing enzymes tyrosine hydroxylase and dopamine beta hydroxylase will be used to examine possible age related changes in afferent inputs tothe LHRH system.