ROLE OF GALANIN IN THE REGULATION OF GONADAL FUNCTIONS

甘丙肽是一种最初从猪肠中分离出来的多肽 广泛分布于中枢神经系统。最近的 合成老鼠分子的可用性使我们能够产生一种 大鼠甘丙素特异性抗血清。在我们实验室的初步研究中，我们 观察到大鼠大脑中的甘丙素免疫反应神经元的一个亚群 下丘脑视前区的形态和位置 与LHRH免疫反应神经元相似。事实上，这些 GAL免疫反应阳性神经元也表达LHRH免疫反应。这 观察表明，GAL可能是一个重要的因素 调节性腺功能。使用孵化系统[弓形核-- 正中隆起(AN-ME)片段]在我们实验室开发和表征， 我们观察到，事实上，大鼠甘丙素能够有效地刺激LHRH 从AN-ME终端体外释放。这种刺激作用是相关联的 自吲哚美辛阻止PG合成以来PGE2的释放，a 环氧合酶抑制剂，可阻断rGAL诱导的LHRH释放。此外， RGAL诱导的LHRH释放需要一个功能正常的去甲肾上腺素系统 自肾上腺素能拮抗剂酚妥拉明和 特异性α1-肾上腺素能拮抗剂，哌唑嗪，能够阻断 RGAL诱导LHRH释放。这些解剖和功能上的关联， 提示GAL和LHRH也可以共分泌。事实上，当 我们分析了rGAL和LHRH释放到垂体门循环的情况。 观察到rGAL释放到门脉循环中。 浓度高于在外周血液中观察到的浓度。此外，rGAL 门脉血液的分泌物以脉动的方式发生，描绘了 与LHRH同时发生的分泌事件。然而，它必须是 注意到几乎所有的rGAL分泌期都在LHRH之前， 提示在LHRH脉冲的产生过程中，GAL可能是触发因素。 这些观察结果为将GAL视为下丘脑提供了依据 参与调节LHRH释放的因子，从而 性腺功能的控制。

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.