EXCITATORY AMINO ACIDS--ROLE IN GNRH, LH & FSH SECRETION

兴奋性氨基酸——在 GNRH、LH 中的作用

• 批准号: 2201458
• 负责人: DARRELL W BRANN
• 金额: $ 9.36万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2201458
• 关键词: NMDA receptors; acetylcholine; dopamine; estradiol; excitatory aminoacid; female; follicle stimulating hormone; glutamate receptor; gonadotropin releasing factor; hormone regulation /control mechanism; hypothalamus; laboratory rat; luteinizing hormone; neuroendocrine system; neuropeptide Y; norepinephrine; ovariectomy; progesterone; prolactin; radioimmunoassay; receptor expression; secretion

This project addresses the fundamental issue of whether excitatory amino acids (EAAs), such as glutamic acid or aspartic acid, are involved in the neuroendocrine regulation of gonadotropin secretion in the female rat. While significant work has been done in the male on this question, surprisingly little work has been performed in the female. Gaining a better understanding of the neuroendocrine events and mechanisms which regulate the gonadotropin surge in the female is important, since it could lead to new ways to regulate reproduction and to new methods for treating infertility. The proposed study will determine the ability of EAAs to regulate GnRH, gonadotropin and prolactin secretion in the female rat using both in vitro and in vivo approaches. In vitro studies will examine the ability of a variety of natural (endogenous) and synthetic EAAs to regulate GnRH release from hypothalami of estrogen-primed ovariectomized (ovx.) adult rats perfused in vitro. The specific receptor mediating each EAA effect will also be determined as will the ability of each EAA to repetitively stimulate GnRH release. EAAs will also be administered in vivo to validate that the effects observed in vitro are real effects that can be observed in the natural in vivo environment. Aim 2 will examine whether EAA effect is influenced by gonadal steroid background. Ovx. rats with and without estradiol or estradiol plus progesterone replacement will be used in this aim. Both in vitro GnRH release and in vivo LH, FSH and PRL release after EAA administration will be assessed in these animals. In Aim 3, specific NMDA and non-NMDA receptor antagonists will be employed in ovx. estrogen-progesterone treated animals, and during the different days of the cycle to determine the physiological role of EAAs in negative and positive feedback regulation. Furthermore, the role of endogenous EAAs in pulsatile GnRH and LH release in the female will also be examined. Aim 4 will determine if the effect of EAAs on GnRH, LH, FSH and prolactin release is mediated through effects on other neurotransmitter systems (catecholamine, acetylcholine and NPY) known to regulate the release of these hormones and releasing hormones. Specific antagonists to each respective system mentioned above will be utilized in vitro and in vivo to answer this question. Also, the possibility that these neurotransmitter systems could use EAAs to mediate their effect on GnRH, gonadotropin or PRL release will be examined. Aim 5 will examine whether steroids can modulate EAA receptor density and affinity in neuroendocrine tissues such as the hypothalamus using ovx. rats with and without steroid replacement, as well as cycling rats on each day of the cycle. These studies will provide important new information on the precise role of EAAs in the regulation GnRH, gonadotropin and prolactin secretion in the female.

这个项目解决了兴奋性氨基是否 谷氨酸或天冬氨酸等酸性物质（EAA）参与其中 女性促性腺激素分泌的神经内分泌调节 大鼠 虽然在这个问题上已经在男性身上做了大量的工作， 令人惊讶的是，在女性中进行的工作很少。 获得了 更好地了解神经内分泌事件和机制， 调节女性的促性腺激素激增是重要的，因为它 可能会导致新的方式来调节生殖和新的方法， 治疗不孕症 拟议的研究将确定EAA调节GnRH的能力， 促性腺激素和催乳素分泌的雌性大鼠使用这两种在 体外和体内方法。 体外研究将检验 多种天然（内源性）和合成EAA调节GnRH 从雌激素引发的卵巢切除（ovx.）成人 体外灌流大鼠。 调节EAA作用的特异性受体 也将确定每个监管局的能力， 刺激GnRH释放。 EAA也将在体内给药， 验证体外观察到的效应是真实的效应， 在自然的体内环境中观察到。 目标2将审查是否 EAA的作用受性腺激素背景的影响。 卵细胞大鼠 如果没有雌二醇或雌二醇加孕酮替代， 用于此目的。 体外GnRH释放和体内LH、FSH和 将在这些动物中评估EAA给药后的PRL释放。 在目标3中，将研究特异性NMDA和非NMDA受体拮抗剂。 在OVX工作雌激素-孕酮治疗的动物，在 周期的不同天，以确定EAA的生理作用 负反馈和正反馈调节。 此外， 在女性中，脉冲式GnRH和LH释放中的内源性EAA也将 接受检查。 目的4将确定EAA对GnRH，LH， FSH和催乳素的释放是通过对其他 已知的神经递质系统（儿茶酚胺、乙酰胆碱和NPY）， 调节这些激素的释放和释放激素。 具体 将使用上述每种相应系统的拮抗剂 来回答这个问题。 另外， 这些神经递质系统可以使用EAA来介导它们的 将检查对GnRH、促性腺激素或PRL释放的影响。 目标5 将研究类固醇是否可以调节EAA受体密度， 在神经内分泌组织如下丘脑中使用OVX的亲和力。 有和没有类固醇替代的大鼠以及骑自行车的大鼠 循环的每一天。 这些研究将提供重要的新 关于EAA在调节GnRH中的确切作用的信息， 促性腺激素和催乳素的分泌。