ROLE OF HORMONES IN THE PROCESSING OF NEURONAL PEPTIDES

这项研究计划的目的是阐明这种机制。 下丘脑神经元潜在的LHRH释放及其调节 类固醇激素。我们的工作假说(由我们的 在上一次赠款支持期间进行的研究)是 铜从撞击LHRH神经元的神经元中释放出来，被 LHRH神经元与分泌颗粒相互作用，这种相互作用 导致多肽的释放。类固醇通过以下途径调节LHRH的释放 修饰铜对LHRH神经元的作用和/或从其他神经元释放铜 神经元。我们的第一个目标是阐明生物化学机制。 铜刺激释放LHRH的过程 作为一种模式系统的中间隆起。为了实现这一目标，我们将 描述时间进程、剂量反应和以下要求 能量、Na+和颗粒态-SH。第二个目标是澄清 类固醇调节大鼠LHRH神经元释放LHRH的机制 雌性和雄性大鼠。为了达到这一目标，我们将研究 类固醇在铜刺激的LHRH释放过程中的作用。检视 类固醇的这种作用的特异性，我们将平行检查， 类固醇对K+刺激的LHRH释放的影响 与铜的刺激作用不同。第三个目标是定义 脑内铜稳态的生化机制。至 实现这一目标，使用K+刺激的脑片释放作为一种 模型，我们将表征铜的释放过程及其区域 在大脑中的分布。此外，我们还将调查 新摄取的[Cu64]的亚细胞分布和释放。一旦这些 定义了生化参数，我们将利用它们来实现 我们第四个目标的目标--阐明 类固醇(性腺和肾上腺)调节大脑中铜的稳态。 了解类固醇调节LHRH释放的机制， 通过调节铜刺激LHRH和LHRH的释放过程 铜释放本身，将提供对一体化监管的洞察 大脑中的过程，因此，进入发育和荷尔蒙 调节大脑功能。

The goal of this research proposal is to elucidate the mechanisms underlying LHRH release from hypothalamic neurons and its regulation by steroid hormones. Our working hypothesis (conceived as a result of our studies conducted during the period of previous grant support) is that copper, released from neurons impinging on LHRH neurons, is taken up by the LHRH neuron, interacts with the secretory granules and this interaction leads to release of the peptide. Steroids regulate LHRH release by modifying copper action on LHRH neuron and/or copper release from other neurons. Our first objective is to elucidate the biochemical mechanism of the process of copper-stimulated release of LHRH, using explants of the median eminence as a model system. To achieve this goal, we will characterize the time course, dose response and the requirements for energy, Na+, and granule -SH. The second objective is to elucidate the mechanisms by which steroids regulate LHRH release from LHRH neurons of female and male rats. To achieve this goal, we will study the effects of steroids on the process of copper-stimulated release of LHRH. To examine the specificity of this effect of steroids, we will examine in parallel, the effects of steroids on K+-stimulated release of LHRH; a process distinct from that stimulated by copper. The third objective is to define the biochemical mechanisms underlying copper homeostasis in the brain. To achieve this goal, using K+-stimulated release from brain slices as a model, we will characterize the process of copper release and its regional distribution in the brain. In addition, we will investigate the uptake, subcellular distribution and release of newly taken up [Cu64]. Once these biochemical parameters are defined, we will utilize them to achieve the goals of our fourth objective - to elucidate the mechanism by which steroids (gonadal and adrenal) regulate copper homeostasis in the brain. An understanding of the mechanisms by which steroids regulate LHRH release, through regulation of the process of copper-stimulated release of LHRH and of copper release per se, will provide insight into integrative regulatory processes in the brain and hence, into developmental and hormonally regulated brain functions.