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

LHRH 作用：CA2、磷脂和花生的作用

• 批准号: 3313104
• 负责人: GARY D SNYDER
• 金额: $ 7.52万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-08-01 至 1988-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3313104
• 关键词: arachidonate; autoradiography; calcium metabolism; cell population study; centrifugation; cyclic AMP; cyclic GMP; cyclic nucleoside monophosphate; diacylglycerols; follicle stimulating hormone; hormone regulation /control mechanism; lipid metabolism; luteinizing hormone; membrane activity; phospholipids; radiotracer; scintillation spectrometry; thin layer chromatography

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.

LHRH刺激LH和FSH分泌是一种复杂的 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已经被证明 刺激一系列的生化反应， 磷脂酰肌醇（PI）循环。 此外，最近有 这些报告表明，LHRH刺激的LH分泌需要 花生四烯酸（AA）的氧化代谢物的形成。 这个项目 专门研究LHRH诱导的生化 以及刺激PI周期和AA的生理后果 新陈代谢. 此外，本提案所述的研究将 考虑PI循环及其代谢产物的相互关系。 机管局及其 代谢物和其他LHRH相关的细胞内事件，如Ca 2 + 动员和蛋白质磷酸化。 所有这些生物化学和 生理事件导致促性腺激素分泌LH。 这些 研究应该提供深入了解激素分泌的控制， 为生理学研究开辟了新的方向， 代谢和类二十烷酸。 这项研究建议使用生物化学和 和生理学方法来实现其主要目标， 生理反应（LH）的生化机制 分泌）至LHRH刺激LH和FSH分泌。 垂体前叶 细胞将在短细胞培养物（1至4天）中进行研究。 期间 培养期间，将细胞用于研究LHRH对PI的影响 代谢、AA代谢、Ca 2+稳态和蛋白质磷酸化。 PI循环的两种初级代谢产物，从初步的 实验中，研究的关键是：1）甘油二酯（DAG）和2）AA。 的 将研究DAG在以下方面的参与：1）PI 循环; 2）蛋白激酶C活化和3）作为AA的来源。 将研究花生四烯酸代谢，以确定其 LHRH诱导的环氧化产物及其在Ca ~（2+）稳态和细胞内环境中的作用 LH分泌。 特别是，新的AA衍生化合物， 仅在促性腺激素释放激素刺激过程中产生， 结构鉴定和确定其生理重要性。 在 发明内容本发明的建议涉及对哺乳动物和哺乳动物的激素分泌的研究， 生理和生化水平，目的是增加信息， LHRH刺激LH分泌机制的已有知识。