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

这个项目解决了兴奋性氨基是否 酸(EaS)，如谷氨酸或天冬氨酸，参与了 女性促性腺激素分泌的神经内分泌调节 老鼠。虽然在这个问题上已经在雄性身上做了大量的工作， 令人惊讶的是，在雌性中进行的工作很少。获得了一个 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很重要，因为它 可能会导致调节生殖的新方法，以及 治疗不孕不育。 拟议的研究将确定EaAS调节GnRH的能力， 雌性大鼠促性腺激素和催乳素的分泌 体外和体内的方法。体外研究将检验这种能力 多种天然(内源性)和合成的EAA调节GnRH 雌激素性卵巢切除(OVX)的下丘脑释放成人 大鼠体外灌流。介导每种EAA效应的特定受体 也将被确定为每个EAA的重复 刺激促性腺激素释放激素释放。EaaS也将在体内注射到 验证在体外观察到的效果是真实的，可以 在自然活体环境中观察。目标2将考察 EAA效应受性腺类固醇背景的影响。OVX。大鼠有 如果没有雌二醇或雌二醇加黄体酮的替代 用于这一目的。促性腺激素释放激素的体外释放和体内的促黄体生成素、卵泡刺激素和 EAA给药后PRL的释放将在这些动物身上进行评估。 在目标3中，特定的NMDA和非NMDA受体拮抗剂将 受雇于OVX。雌激素-黄体酮处理的动物，在 不同的周期天数来确定EAAS的生理作用 在负反馈和正反馈调节中。此外，中国的作用是 内源性促性腺激素释放激素在雌性体内的搏动性释放也会 接受检查。目标4将确定EaAs对GnRH、Lh、 促卵泡刺激素和催乳素的释放是通过影响其他 神经递质系统(儿茶酚胺、乙酰胆碱和神经肽Y)已知 调节这些激素的释放，释放荷尔蒙。特定的 将使用上述每个相应系统的拮抗剂 在体外和体内回答这个问题。另外，有可能 这些神经递质系统可以使用EaaS来调节它们的 将检测对促性腺激素释放激素、促性腺激素或催乳素释放的影响。目标5 将研究类固醇是否可以调节EAA受体密度和 使用OVX在神经内分泌组织(如下丘脑)中的亲和力。 使用和不使用类固醇替代的大鼠，以及骑自行车的大鼠 在这个周期的每一天。这些研究将提供重要的新的 关于EaaS在调节GnRH中的确切作用的信息， 女性促性腺激素和催乳素的分泌。

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.