ROLE OF GALANIN IN THE REGULATION OF GONADAL FUNCTIONS

我们早期的研究已经证实甘丙素(GAL)是一种重要的 神经调节剂，参与性腺功能的调节。这个 GAL的作用在不同的水平上施加在 下丘脑-垂体-性腺轴。半乳糖刺激LHRH的分泌 弓状核-正中隆起(AN-ME)片段体外孵育， 需要一个功能正常的去甲肾上腺素系统。它还能够刺激 促黄体生成素分泌和促进促黄体生成素释放 脑下垂体前叶的水平。因为GAL被分泌到 垂体门静脉循环的浓度高于观察到的浓度 在外周血液中，该肽应被认为是 下丘脑激素家族。在过去的一年里，我们探索了 内源性GAL是否调节生理事件以及 下丘脑GAL分泌的调节。我们已经证明了 内源性GAL参与了导致胚胎发生的机制。 促黄体生成素和催乳素的排卵前峰值。此外，我们还开发了一种 孵化方案使我们能够测量AN-ME中GAL的释放 并评价几种经典神经递质在血管紧张素系统中的作用。 Gal Release。在旨在建立这种孵化的初步研究中 协议，我们观察到GAL从AN-ME释放，但没有从ME释放 碎片，呈现出一个由指数组成的释放时间进程 先是增长期，然后是平台期。这表明 在孵育液中积累的Gal可能会阻止 多肽。在与Merchenthaler博士和Liposits博士的合作下，我们 启动了一系列实验，旨在评估GAL神经元 在AN内可以在它们之间连接以调节它们自己的 放行速度。因此，我们已经证明了泛函 位于内侧核的甘氨酸能网络，可以调节自身的放电 通过负的超短路反馈机制进行活动。因此，我们的 研究表明，半乳糖，一种最先在肠道中发现的多肽， 构成一种下丘脑促垂体激素，它具有 在生殖功能调节中的生理作用。

Our earlier studies have established that galanin (GAL) is an important neuromodulator involved in the regulation of gonadal functions. The actions of GAL are exerted at different levels in the hypothalamic-pituitary-gonadal axis. GAL stimulates LHRH secretion from arcuate nucleus-median eminence (AN-ME) fragments incubated in vitro, requiring a functional noradrenergic.system. It is also able to stimulate LH secretion and enhance LHRH-induced LH release by acting directly at the level of the anterior pituitary gland. Since GAL is secreted into the hypophyseal portal circulation in higher concentrations than those observed in peripheral blood, the peptide should be considered as a member of the hypothalamic hormone family. During the past year, we have explored whether endogenous GAL regulates physiological events as well as aspects of the regulation of hypothalamic secretion of GAL. We have demonstrated that endogenous GAL is involved in the mechanisms which lead to the origination of the preovulatory surges of LH and PRL. In addition, we developed an incubation protocol which enables us to measure GAL release from AN-ME in vitro and to evaluate the role of several classical neurotransmitters on GAL release. In initial studies aimed to establish this incubation protocol, we observed that GAL release from AN-ME, but not from ME fragments, presented a release time-course consisting of an exponential increasing phase followed by a plateau releasing period. This indicated that GAL accumulating in the incubation medium could stop the release of the peptide. In collaboration with Drs. Merchenthaler and Liposits, we initiated a series of experiments designed to evaluate whether GAL neurons within the AN could be connected between them for regulating their own release rate. As a result, we have shown the existence of a functional galaninergic network located in the AN, which can regulate its own firing activity via a negative ultrashortloop feedback mechanism. Therefore, our studies have shown that GAL, a peptide first discovered in the gut, constitutes a hypothalamic hypophysiotropic hormone which has a physiological role in the regulation of reproductive functions.