LHRH ACTION: ROLES OF CA2+, PHOSPHOLIPIDS, AND ARACHIDO

促黄体生成素和卵泡刺激素的分泌是一种复合体的结果。 一系列的生化反应。其中一些是已知的，但 这些事件的整合是不完整的。最近，LHRH被展示出来 刺激一系列的生化反应被指定为 磷脂酰肌醇(PI)循环。此外，最近还出现了 有报道表明促性腺激素释放激素刺激的促黄体生成素分泌需要 花生四烯酸(AA)含氧代谢产物的形成。这个项目 旨在专门研究LHRH诱导的生物化学 以及刺激PI循环和AA的生理后果 新陈代谢。此外，本提案中描述的研究将 考虑PI循环及其代谢物之间的相互关系。机管局及其智能交通系统 代谢物和其他与LHRH相关的细胞内事件，如钙离子 动员和蛋白质磷酸化。所有这些生化和 生理事件导致促性腺激素分泌黄体生成素。这些 研究应该提供对激素分泌控制的洞察力 为生理学和生理学的研究开辟了新的方向 新陈代谢和二十烷类化合物。这项研究既使用了生物化学，也使用了生物化学 和生理学方法论来实现它的主要目标 参与生理反应的生化机制(黄体生成素 分泌)对LHRH刺激促黄体生成素和卵泡刺激素分泌的作用。垂体前叶 细胞将在短期细胞培养(1-4天)中进行研究。在.期间 培养期间细胞将用于研究LHRH对猪的影响 代谢、AA代谢、钙动态平衡和蛋白质磷酸化。 PI循环的两种主要代谢物，从初步看来 实验：1)甘油二酯(DAG)和2)AA。这个 将根据DAG在1)PI中的角色来研究其参与 循环；2)蛋白激酶C的激活；3)作为AA的来源。 将对花生四烯酸代谢进行研究，以确定其 促性腺激素释放激素诱导的环氧化产物及其在钙动态平衡和细胞周期中的作用 促黄体生成素分泌。特别是，新的AA衍生化合物显然是 仅在促性腺激素释放激素刺激期间产生 在结构上进行了鉴定，并确定了它们的生理重要性。在……里面 摘要这一建议接近于对两种动物的激素分泌的研究 生理和生化水平，目标是增加信息 对促黄体生成素刺激促黄体生成素分泌的机制已有了解。

The stimulation of LH and FSH secretion by LHRH is the result of a complex series of biochemical reactions. Some of these are known, but the integration of these events is incomplete. Recently, LHRH has been shown to stimulate the series of biochemical reactions designated as the phosphatidylinositol (PI) cycle. Moreover, recently there have been reports that are suggestive that LHRH-stimulated LH secretion requires the formation of oxygenated metabolites of arachidonic acid (AA). This project has been designed to investigate specifically the LHRH-induced biochemstry and physiological consequences of the stimulation of the PI cycle and AA metabolism. In addition, the studies described in this proposal will consider the interrelation of the PI cycle and its metabolites. AA and its metabolites and other LHRH-related intracellular events such as Ca2+ mobilization and protein phosphorylation. All of these biochemical and physiological events lead to secretion of LH from the gonadotroph. These studies should provide insight into the control of hormone secretion in general as well as open new directions for research into the physiology and metabolism and the eicosanoids. The study proposed uses both biochemical and physiological methodologies to accomplish its primary goal of relating the biochemical mechanisms involved in the physiological response (LH secretion) to LHRH stimulation of LH and FSH secretion. Anterior pituitary cells are to be studied in a short cell culture (1 to 4 days). During the culture period the cells will be used to study the effects of LHRH on PI metabolism, AA metabolism, Ca2+ homeostasis and protein phosphorylation. Two primary metabolites of the PI cycle, appear from preliminary experiments, to be key for study: 1) diacylglycerol (DAG) and 2) AA. The involvement of DAG will be sutdied with respect to its roles in 1) the PI cycle; 2) protein kinase C activation and 3) as a source of AA. Arachidonic acid metabolism will be investigated to ascertain its LHRH-induced epoxygenation products and their roles in Ca2+ homeostasis and LH secretion. In particular, new AA-derived compounds which are apparently produced only during LHRH-stimulation of the gonadotroph will be structurally identified and their physiological importance ascertained. In summary this proposal approaches the study of hormone secretion of both the physiological and biochemical levels with a goal of adding information to pre-existing knowledge of the mechanism of LHRH-stimulated LH secretion.