GONADOTROPIN RECEPTORS OF THE PRIMATE CORPUS LUTEUM

灵长类黄体的促性腺激素受体

• 批准号: 3319318
• 负责人: RICHARD L STOUFFER
• 金额: $ 15.71万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3319318
• 关键词: G protein; Macaca mulatta; SDS polyacrylamide gel electrophoresis; adenosine diphosphate; adenosine triphosphate; adenylate cyclase; blood chemistry; chemical structure function; chorionic gonadotropin; corpus luteum; crosslink; cyclic AMP; diacylglycerols; eicosanoid metabolism; gel electrophoresis; gel filtration chromatography; gonadotropins; hormone receptor; hormone regulation /control mechanism; laboratory rat; luteinizing hormone; menstrual cycle; nucleotide analog; pregnancy; progesterone; prostaglandins; radioimmunoassay; radiotracer; receptor coupling; second messengers; steroid biosynthesis

The proposed research is designed to test the hypothesis that modulation of gonadotropin receptors, their intracellular messenger systems (e.g., adenylate cyclase) or the coupling of these membrane components is an important mechanism regulating the primate corpus luteum during the menstrual cycle and early pregnancy. Based on progress in this laboratory, the metabolism of arachidonic acid in the corpus luteum will be modified: (1) to identify products (e.g., prostaglandins) , which have local luteotropic or luteolytic actions during the menstrual cycle, and (2) to examine the effects of these paracrine factors on the gonadotropin receptor-adenylate cyclase system in luteal tissue. Studies are also planned in a novel model of early pregnancy: (3) to investigate the mechanisms resulting in homologous desensitization of adenylate cyclase in the primate corpus luteum during CG exposure, and (4) to define the relationship between changes in the gonadotropin receptor-adenylate cyclase system and the steroidogenic and peptidergic funtions of the corpus luteum. The adult, female rhesus monkey continues as the animal of choice for this project. Arachidonate metabolism will be modulated and monitored by drug infusions directly into the corpus luteum and blood collection from the utero-ovarian vein (and aorta), respectively. Levels of progesterone, LH and prostaglandins in the blood will be measured by radioimmunoassay. A regimen of human CG which invokes pregnancy-like patterns of circulating gonadotropin will be employed to simulate the rescue of the corpus luteum in early pregnancy. Adenylate cyclase activity will be assessed by the conversion of (alpha 32P)ATP to (32P) cyclic AMP. Available and occupied receptors will be characterized via specific 125I-hCG binding and radioimmunoassay of eluted CG, respectively. Crosslinked (125I)hCG-receptors will be solubilized and subjected to column chromatography and SDS-gel electrophoresis. Luteal cells from simulated early pregnancy will be incubated in vitro to discern their response to gonadotropins, prostaglandins and analogs of intracellular messengers (e.g., dibutryl cyclic AMP, a Ca+2 ionophore A23178 and oleoylacetylglycerol). These studies will (a) broaden our understanding of the gonadotropin receptor-second messenger systems in primate species, and (b) help elucidate the endocrine and paracrine processes regulating luteal function during the menstrual cycle and early pregnancy, with direct application to controlling fertility and infertility in women.

拟议的研究旨在检验以下假设 促性腺激素受体的调节，其细胞内信使 系统（例如腺苷酸环化酶）或这些膜的偶联 组件是调节灵长类动物语料库的重要机制 在月经周期和早期怀孕期间的叶片。 基于 在这个实验室的进展，蛛网膜酸在 Luteum将被修改：（1）识别产品（例如， 前列腺素），具有局部黄质或黄体溶液 月经周期期间的作用，（2）检查效果 在促性腺激素受体 - 腺苷的这些旁分泌因子中 黄体组织中的环化酶系统。 还计划了 早期怀孕的新型模型：（3）研究机制 导致腺苷酸环化酶在 在CG暴露期间，灵长类动物曲目，（4）定义 促性腺激素受体 - 腺苷酸的变化之间的关系 环化酶系统以及类固醇生成和替代性功能 Luteum。 成年雌性恒河猴继续作为选择的动物 对于这个项目。 蛛形代谢将受到调节，并且 通过药物输注直接监测到Luteum和 子宫卵巢静脉（和主动脉）的血液收集， 分别。 孕酮，LH和前列腺素的水平 血液将通过放射免疫测定法测量。 人类CG方案 引用循环促性腺激素的妊娠样模式 将被用来模拟Luteum的营救 在怀孕初期。 将评估腺苷酸环化酶活性 通过（Alpha 32p）ATP转换为（32p）循环AMP。 可用的 并通过特定的125i-HCG表征被占用的受体 洗脱CG的结合和放射免疫测定法。 交联（125i）HCG受体将被溶解并进行 到柱色谱和SDS-凝胶电泳。 黄体细胞 从模拟的早期怀孕将在体外孵育至 辨别他们对促性腺激素，前列腺素和类似物的反应 细胞内信使（例如，二核素循环AMP，a ca+2 离子载体A23178和油酰乙酰甘油）。 这些研究将（a）扩大我们对 灵长类动物中的促性腺激素受体 - 元素系统， （b）帮助阐明内分泌和旁分泌过程 在月经周期和早期调节黄体功能 怀孕，直接应用于控制生育能力和 女性不孕。