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: 3877014
• 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/3877014
• 关键词: hormone regulation /control mechanism; hypothalamus; indomethacin; intestines; laboratory rat; median eminence; neurons; neuropeptides; phentolamine; portal vein; prazosin; preoptic areas; prostaglandin E

Galanin is a peptide originally isolated from porcine intestine and shown to be vastly distributed in the central nervous system. The recent availability of the synthetic rat molecule allowed us to generate a specific antiserum against rat galanin. In initial studies from our lab, we observed that a subset of rat galanin-immunoreactive neurons in the preoptic area of the hypothalamus presented a morphology and location similar to that of LHRH-immunoreactive neurons. In fact, these GAL-immunoreactive neurons also expressed LHRH immunoreactivity. This observation suggested to us that GAL could be an important factor in regulating gonadal functions. Using an incubation system [arcuate nucleus-- median eminence (AN-ME) fragments] developed and characterized in our lab, we observed that, indeed, rat galanin was able to potently stimulate LHRH release from AN-ME terminals in vitro. This stimulatory action was linked to PGE2 release since the blockade of PG synthesis using indomethacin, a cyclooxygenase inhibitor, abolished rGAL-induced LHRH release. Moreover, rGAL-induced LHRH release requires a functional noradrenergic system to be expressed since an a adrenergic antagonist, phentolamine, as well as a specific alpha1-adrenergic antagonist, prazosin, were able to block rGAL-induced LHRH release. These anatomical and functional correlates, indicated to us that GAL and LHRH could be also co-secreted. Indeed, when we analyzed rGAL and LHRH release into the hypophyseal portal circulation it was observed that rGAL is released into the portal circulation in higher concentrations than those observed in peripheral blood. Furthermore, rGAL secretion into the portal blood occurred in a pulsatile fashion, depicting secretory events that coincided with those of LHRH. However, it must be noted that practically all rGAL secretory episodes preceded those of LHRH, suggesting that in the generation of a LHRH pulse GAL may be the trigger. These observations provide the basis for considering GAL as a hypothalamic factor participating in the regulation of LHRH release and, thereby, the control of gonadal functions.

甘丙肽是最初从猪肠分离的肽， 广泛分布在中枢神经系统中。近期 合成老鼠分子的可用性使我们能够产生一种 抗大鼠甘丙肽特异性抗血清。在我们实验室的初步研究中，我们 观察到，大鼠脑内甘丙肽免疫反应神经元的一个子集， 下丘脑视前区的形态和位置 类似于LHRH免疫反应神经元。其实这些 GAL免疫反应神经元也表达LHRH免疫反应性。这 观察表明，GAL可能是一个重要因素， 调节性腺功能使用一个孵化系统[弓状核-- 正中隆起（AN-ME）碎片]在我们的实验室开发和表征， 我们观察到，大鼠甘丙肽确实能够有效地刺激LHRH， 体外从AN-ME末端释放。这种刺激作用与 由于使用吲哚美辛阻断PG合成， 环氧合酶抑制剂，废除rGAL诱导的LHRH释放。此外，委员会认为， rGAL诱导的LHRH释放需要功能性去甲肾上腺素能系统， 由于肾上腺素能拮抗剂酚妥拉明以及 特异性α 1-肾上腺素能拮抗剂哌唑嗪能够阻断 rGAL诱导的LHRH释放。这些解剖学和功能的相关性， 提示GAL和LHRH也可以共分泌。其实，当 我们分析了rGAL和LHRH释放到垂体门静脉循环中， 观察到rGAL在较高的肝细胞中释放到门静脉循环中， 浓度高于外周血中观察到的浓度。此外，rGAL 以脉动方式分泌到门静脉血中， 与LHRH的分泌事件一致。但必须 注意到几乎所有的rGAL分泌期都先于LHRH的分泌期， 这表明在LHRH脉冲的产生中GAL可能是触发器。 这些观察结果提供了考虑GAL作为下丘脑的基础。 参与调节LHRH释放的因子，从而， 控制性腺功能。