ROLE OF GALANIN IN THE REGULATION OF GONADAL FUNCTIONS

甘丙肽在性腺功能调节中的作用

• 批准号: 3856001
• 负责人: F J LOPEZ
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3856001
• 关键词: hormone regulation /control mechanism; hypothalamus; luteinizing hormone; neurons; neuropeptides; neurotransmitters; portal vein

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.

我们早期的研究已经确定甘丙肽（GAL）是一种重要的 参与性腺功能调节的神经调质。 的 GAL的行动在不同层面上发挥作用 下丘脑垂体性腺轴 GAL刺激LHRH分泌， 弓状核-正中隆起（AN-ME）片段在体外孵育， 需要功能性去甲肾上腺素能系统。它还能刺激 LH分泌和增强LHRH诱导的LH释放直接作用于 垂体前叶水平。 由于GAL被分泌到 垂体门脉循环浓度高于观察到的浓度 在外周血中，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 对下丘脑GAL分泌的调节。 我们已经证明 内源性GAL参与了导致起源的机制， 排卵前LH和PRL的激增。 此外，我们还开发了一个 孵育方案使我们能够测量GAL从AN-ME中的释放， 并评估几种经典的神经递质对 GAL释放 在最初的研究中， 方案中，我们观察到GAL从AN-ME释放，而不是从ME释放 碎片，提出了一个释放时间过程组成的指数 增加阶段之后是平台释放期。 这表明 GAL在培养介质中的积累可以阻止 肽。 与Merchenthaler博士和Liposits博士合作，我们 启动了一系列旨在评估GAL神经元 在AN内，可以在它们之间连接，以调节它们自己的 释放率 因此，我们证明了存在一个泛函 位于AN中的甘丙肽能网络，其可以调节自身的放电 通过一个负的超短循环反馈机制。 所以我们的 研究表明，GAL，一种首先在肠道中发现的肽， 构成下丘脑促垂体激素，其具有 在生殖功能调节中的生理作用。