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变化 在发情前期黄体生成素激增的模式中，最后完全消失 周期黄体生成素激增。增龄过程中黄体生成素分泌模式的增龄变化 雌性被认为最终是由于LHRH被改变释放到 脑下垂体门脉系统。目前很少有信息显示 然而，关于LHRH在老年雌性大鼠中的释放。这个 这里提出的一系列实验将表征LHRH神经分泌 在衰老的雌性大鼠身上，他们将确定1)在 LHRH的释放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LHRH内的改变 神经元本身导致了生育能力的丧失。在实验1中， 将使用推挽式灌注来表征LHRH的模式 中青年女性发情前期或发情期分泌物的变化 在卵巢切除和类固醇注射之后。如果更改了 LHRH释放的脉动模式的幅度或频率为 在老化的动物身上观察到，将试图逆转这些 服用肾上腺素能激动剂后的变化。在实验2中，LHRH 正中隆起的孤立神经末梢的神经分泌将 非特异性(K+)和特异性(PGE2，NE)后的体外检测 刺激。这种方法将允许检查可能与年龄有关的 下丘脑LHRH储备物与其他药物的释放性变化 年龄相关的变化，例如，在传入输入中，这也可能起到 在体内改变LHRH的释放。在实验3中，LHRH的反应 以下是中青年女性的制度 电刺激内侧视前区(100-60秒)。 实验3的结果将决定LHRH系统是否在 衰老的雌性大鼠保持对刺激引起的反应的能力 对合成和释放的需求增加。最后，免疫细胞化学 在实验4中将使用一些技术来研究 儿茶酚胺能系统和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 酪氨酸羟基酶和多巴胺β羟基酶将用于检测 LHRH系统的传入输入可能与年龄相关的变化。

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.