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: 3777583
• 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/3777583
• 关键词: 3 methoxy 4 hydroxyphenylethyleneglycol; 3,4 dihydroxyphenylacetate; brain metabolism; catecholamines; dopamine; estrus; female; follicle stimulating hormone; hormone regulation /control mechanism; hydroxyindoleacetate; hypothalamic pituitary axis; hypothalamus; laboratory rat; median eminence; neuropeptides; neuropharmacology; neutralizing antibody; norepinephrine; oogenesis; paracrine; passive immunization; prolactin; secretion; serotonin

Endogenous galanin (GAL) has emerged as a physiological regulator of the preovulatory surge of LH and prolactin. Early studies from our group have uncovered several sites where the peptide acts to control the secretion of some pituitary hormones. First, GAL acts at the hypothalamic level and, more specifically on LHRH neurons, to increase the release of the neuropeptide LHRH. In addition, GALergic neuronal systems, including LHRH, release GAL into the hypophyseal portal circulation so that, after reaching the anterior pituitary gland. it can modulate basal or stimulated release of adenohypophyseal hormones. Intrapituitary-synthesized GAL can participate in local modulation by paracrine mechanism. Since classical neurotransmitters, such as catecholamines and serotonin, are involved in the mechanisms involved in the genesis of the preovulatory release of gonadotropins and prolactin, we hypothesized that the effects of endogenous GAL previously observed on the proestrous surge of LH and PRL could be mediated, at least in part, by alterations in brain catecholamine and serotonin turnover rates. In initial studies, we have evaluated catecholamine and serotonin, as well as their primary metabolite levels in the median eminence (ME) in a passive immunization paradigm against GAL during proestrus. Using this model, we observed that blockade of endogenous GAL blunts the preovulatory surges of LH and PRL without altering the FSH surge. Under these conditions, norepinephrine (NE) and dopamine (DA) levels in the ME did not change at 1600 and 1900 h regardless of the treatment. In contrast, serotonin (5HT) levels were elevated in GAL antiserum (GAL-AS)- treated rats. Treatment with GAL-AS did not alter 3-methoxy-4- hydroxyphenylethyleneglycol (MHPG; the primary metabolite of NE) levels in the ME. The levels of 3,4-dihydroxyphenyl-acetic acid (DOPAC; the primary metabolite of DA) were reduced at 1900 h in control animals when compared to 1600 h. In contrast, GAL-AS administration reduced significantly (DOPAC) at 1600 h. This effect was also observed in 5- hydroxyindol-3-acetic acid levels (5HIAA; the primary metabolite of 5HT). The evaluation of amine metabolism ratio between metabolite and amine levels) revealed that GAL-AS administration reduced between DA and 5HT metabolism at 1600 h without altering the rate in NE. In summary. these data indicate that endogenous GAL controls the preovulatory surge of LH and PRL with a concomitant alteration in the metabolism of DA and 5HT.

内源性甘丙肽（GAL）已经作为一种生理调节剂出现， 排卵前LH和催乳素激增。 我们小组的早期研究 已经发现了几个位点，在这些位点上肽可以控制 一些垂体激素的分泌。 首先，GAL在 下丘脑水平，更具体地对LHRH神经元，以增加 神经肽LHRH的释放。 此外，GAL能神经元 系统，包括LHRH，将GAL释放到垂体门静脉 循环，以便在到达脑垂体前叶后。它可以 调节腺垂体激素的基础或刺激释放。 垂体内合成的GAL可以通过以下方式参与局部调节： 旁分泌机制 因为经典的神经递质，如 儿茶酚胺和血清素参与了 排卵前促性腺激素和催乳素释放的发生， 我们假设先前观察到的内源性GAL的作用 对LH和PRL的动情前期峰的影响至少在 部分是通过改变脑中的儿茶酚胺和5-羟色胺的周转率。 在最初的研究中，我们评估了儿茶酚胺和血清素， 以及它们在正中隆起（ME）中的初级代谢物水平， 在发情前期针对GAL的被动免疫模式。 使用此 模型中，我们观察到内源性GAL的阻断会钝化 排卵前LH和PRL激增而不改变FSH激增。 下 这些条件下，ME中的去甲肾上腺素（NE）和多巴胺（DA）水平 在1600和1900 h，无论处理如何，均未发生变化。 在 相反，血清素（5 HT）水平在GAL抗血清（GAL-AS）中升高。 治疗的老鼠 用GAL-AS处理不改变3-甲氧基-4-甲氧基-N-甲基-N-（3-甲氧基-4-甲氧基苯基）-N-（3-甲氧基苯基）-N 羟苯基乙二醇（MHPG; NE的主要代谢产物）水平 3，4-二羟基苯乙酸（DOPAC; DA的主要代谢产物）在1900 h时在对照动物中减少， 与1600小时相比。 相比之下，GAL-AS给药降低了 在1600 h时显著（DOPAC）。 在5- 10天内也观察到这种效应。 羟基吲哚-3-乙酸水平（5 HIAA; 5 HT的主要代谢产物）。 代谢产物与胺代谢比值的评价 水平）显示，GAL-AS给药降低了DA和5 HT之间的 在1600 h时代谢无变化。 总之。这些 数据表明内源性GAL控制排卵前LH峰 和催乳素，并伴随着DA和5-HT代谢的改变。