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: 3841180
• 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/3841180
• 关键词: autocrine; hormone regulation /control mechanism; hypothalamic pituitary axis; hypothalamus; luteinizing hormone; neuroendocrine system; neuropeptides; paracrine; pituitary gonadal axis; secretion; tissue /cell culture

Studies from our laboratory have provided the basis for considering galanin (GAL) as a neuroendocrine modulator and/or regulator, which participates in the control of gonadal functions. The actions of GAL on the reproductive axis are exerted by endocrine, autocrine and paracrine mechanisms. During the last year, we have provided compelling evidence for most of these mechanisms as well as established a physiological role for the peptide in the control of reproductive events such as the hormonal surges associated with ovulation. Examples for endocrine, autocrine and paracrine regulation by GAL are: the active secretion of the peptide into the hypophyseal portal circulation, the ability of GAL to regulate its own secretion rate from the arcuate nucleus GALergic network, and the actions of GAL secreted from certain pituitary cells for modulating the secretion of others, respectively. Galanin is able to regulate LHRH secretion from arcuate nucleus-median eminence fragments in vitro and requires intact noradrenergic and prostaglandin systems for expressing its effects. Although this constitutes an important observation, the characteristics of the experimental approach do not allow one to distinguish whether the actions of GAL are exhibited directly on the LHRH neuron or are mediated through an interneuronal system. Recently, we have undertaken this question by evaluating the effects of GAL on LHRH secretion from an immortalized LHRH neuronal line. The preliminary results indicate that the peptide has a direct action on RH neurons to enhance their secretory activity. Since GAL is secreted into the portal vasculature, it could act at the level of the gonadotrophs to both stimulate basal secretion and enhance LHRH-induced LH release. However, recent studies have indicated that GAL synthesized within the pituitary contributes to the final gonadotropin output from the pituitary. Using an anti-GAL serum developed in our laboratory, we have been able to show that the blockade of GAL actions in dispersed pituitary cells reduces basal LH secretion. Therefore, GAL is a hypothalamic-hypophysiotropic hormone which regulates, under physiological conditions, LH secretion by acting at the level of the LHRH neuronal system and the pituitary gland as either an endocrine (GAL in portal circulation) or paracrine (intrapituitary GAL) regulator.

我们实验室的研究为考虑甘丙肽提供了基础 (GAL)作为神经内分泌调节剂和/或调节剂，其参与 性腺功能的控制。 GAL对生殖系统的作用 轴是由内分泌，自分泌和旁分泌机制。 期间 去年，我们为其中大多数提供了令人信服的证据， 机制，以及建立了生理作用的肽， 控制生殖活动，如与生殖相关的激素激增， 排卵期。 内分泌、自分泌和旁分泌调节的实例 通过GAL是：主动分泌肽到垂体 门脉循环，GAL调节自身分泌速率的能力 从弓状核GAL能网络，和GAL分泌的行动， 从某些脑垂体细胞中提取来调节其他细胞的分泌， 分别 甘丙肽能够调节弓形虫LHRH的分泌 核-正中隆起碎片在体外，需要完整的 去甲肾上腺素能和前列腺素系统表达其作用。 虽然这是一个重要的观察结果， 实验方法不允许区分是否 GAL的作用直接表现在LHRH神经元上或通过 通过神经元间系统。 最近，我们已着手 通过评估GAL对LHRH分泌的影响， 永生化LHRH神经元系。 初步结果表明， 肽对RH神经元具有直接作用，以增强其分泌 活动 由于GAL被分泌到门静脉血管系统中，它可以起作用， 在促性腺激素细胞水平刺激基础分泌， 增强LHRH诱导的LH释放。 然而，最近的研究表明， 脑垂体内合成的GAL有助于最终的 垂体分泌的促性腺激素 使用一种抗GAL血清 在我们的实验室里，我们已经能够证明，GAL的封锁， 分散的垂体细胞的作用减少了基础LH分泌。 因此，GAL是一种下丘脑促垂体激素， 在生理条件下，LH分泌通过作用于 LHRH神经系统和脑垂体作为内分泌（GAL在 门静脉循环）或旁分泌（垂体内GAL）调节剂。