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

在过去5年中取得的重大进展确立了 兴奋性氨基酸递质(EaAs)在中枢神经系统中发挥重要作用。 促性腺激素释放激素神经分泌的控制。续签提案的重点是澄清 EaaS调节GnRH分泌的机制，以及进一步 描述神经内分泌信号的序列/相互作用 诱导排卵前促黄体生成素高峰。目标1将决定 一氧化氮(NO)作为EAA效应的下游介导物 下丘脑控制促性腺激素释放激素和黄体生成素的分泌。EaaS对企业的影响 将评估下丘脑NO的产生，以及基本问题 一氧化氮的产生是否受到类固醇的调节，并在 发情前期黄体生成素高峰时间。目标2将确定阿片类神经元 调节抑制下丘脑谷氨酸和/或NO神经元的功能 纳洛酮对下丘脑谷氨酸和一氧化氮释放的影响 制作。目标3号将确定精确的第二信使系统 谷氨酸和一氧化氮用来调节促性腺激素释放激素和黄体生成素的释放。下丘脑 第二信使鸟苷环化酶和环氧合酶的表达， 将在周期和排卵前促黄体生成素高峰期间确定，以及 在给予谷氨酸和/或不使用任何药剂之后。酶抑制剂 还将用于确定这些系统的功能重要性。 目标4将确定谷氨酸神经信号传导的缺陷是否 通过确定EAA受体、EAA是否参与生殖衰老 下丘脑的释放率和NO的产生减弱。 发情前期下午的中年大鼠。目标5将确定是否 在大脑中合成一氧化碳的血红素加氧酶具有 在黄体生成素峰的产生中起生理作用，并受 谷氨酸和/或类固醇。目标6将确定类固醇激素是否 控制下丘脑谷氨酸转运体表达是其作用机制之一 调节突触处的谷氨酸水平。这些研究将加强我们的 对GnRH和GnRH的复杂神经内分泌机制的认识 雌性黄体生成素的分泌。

Significant progress within the last 5 years has established that excitatory amino acid transmitters (EAAs) play a central role in the control of GnRH neurosecretion. The renewal proposal focuses on elucidating the mechanisms utilized by EAAs to regulate GnRH secretion, and further delineating the sequence/interaction of neuroendocrine signals in the induction of the preovulatory LH surge. Aim 1 will determine the role of nitric oxide (NO) as a downstream mediator of EAA effects in the hypothalamus to control GnRH and LH secretion. The effect of EAAs on hypothalamic NO production will be evaluated as will the essential question of whether NO production is regulated by steroids and is elevated at the time of the proestrus LH surge. Aim 2 will determine whether opioid neurons function to tonically inhibit hypothalamic glutamate and/or NO neurons by examining the effect of naloxone on hypothalamic glutamate release and NO production. Aim 3 will determine the precise second messenger systems utilized by glutamate and NO to regulate GnRH and LH release. Hypothalamic expression of the second messenger, guanylate cyclase and cyclooxygenase, will be determined during the cycle and the preovulatory LH surge, and following administration of glutamate and/or NO agents. Enzyme inhibitors will also be used to determine functional significance of these systems. Aim 4 will determine whether a defect in glutamate neurosignaling is involved in reproductive aging by determining whether EAA receptors, EAA release rates and NO production are attenuated in the hypothalamus of the middle-aged rat on proestrus afternoon. Aim 5 will establish whether the enzyme heme oxygenase, which synthesizes carbon monoxide in the brain, has a physiological role in production of the LH surge and is regulated by glutamate and/or steroids. Aim 6 will establish whether steroid hormones control hypothalamic glutamate transporter expression as a mechanism of regulating glutamate levels at the synapse. These studies will enhance our understanding of the complex neuroendocrine mechanisms controlling GnRH and LH secretion in the female.