REGULATION OF LH RECEPTORS AND PROGESTERONE SECRETION

LH 受体和孕酮分泌的调节

• 批准号: 3311612
• 负责人: TORRANCE M NETT
• 金额: $ 1.39万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3311612
• 关键词: adenylate cyclase; binding proteins; cell cell interaction; chorionic gonadotropin; corpus luteum; estrus; graafian follicles; guanine nucleotide binding protein; guanosine triphosphate; hormone receptor; hormone regulation /control mechanism; luteinizing hormone; monoclonal antibody; pregnancy; progesterone; prostaglandin E; prostaglandin F; sheep

Progesterone secretion by the corpus luteum is essential for normal pregnancy. Thus, methods to interrupt secretion of this hormone have potential contraceptive applications. In addition, biological anomolies in this system cause infertility in some couples. The first step in stimulation of progesterone secretion by luteinizing hormone (LH) is the interaction of the hormone with its receptor. Therefore, experiments are proposed to characterize further this interaction. First, differences in the biological response of luteal cells to human chorionic gonadotropin (hCG) and luteinizing hormone (LH), which interact with the same receptor, will be studied. The effects of pulses of the two hormones on progesterone secretion by slices of luteal tissue in a perifusion system will be examined to determine if hCG induces a prolonged steroidogenic response, as seen in other tissues. Since it is known that hCG-LH receptor complexes remain on the surface of luteal cells 50 times longer than LH-LH receptor complexes we will also compare the lateral mobility of hCG-LH receptor complexes and LH-LH receptor complexes in luteal cell membranes using a laser photobleach recovery technique. Second, recent identification and characterization of two types of steroidogenic luteal cells lead to experiments designed to: 1) identify the luteal cell types which originate from follicular granulosal and thecal cells; 2) characterize the cell type(s) which bind LH, and PGF(2 alpha) in vivo; and 3) define the nature of the cell-to-cell interactions which results in luteal regression during the reproductive cycle or maintenance of the corpus luteum during pregnancy. In vivo and in vitro procedures will be used in these studies. Third, since secretion of progesterone by the corpus luteum appears to be more dependent upon the number of receptors present for LH than on the levels of this hormone in blood, the mechanisms involved in loss and renewal of receptors for LH will be studied using monoclonal antibodies against the LH receptor and/or methods which allow LH or hCG to be covalently linked to the receptor. Finally, the role of the GTP-binding protein in hormonal activation of adenylate cyclase will be studied using photoaffinity analogs of GTP. The results of these studies will provide new information regarding the complex biological mechanisms which regulate progesterone secretion from the corpus luteum.

黄体的孕酮分泌对于正常的 怀孕 因此，中断这种激素分泌的方法有 潜在的避孕应用。 此外，生物学上的反常现象， 这个系统会导致一些夫妇不孕。 的第一步 促黄体生成素（LH）刺激孕酮分泌是 激素与其受体的相互作用。 因此，实验 建议进一步描述这种相互作用。 第一，差异 黄体细胞对人绒毛膜促性腺激素的生物学反应 (hCG)和促黄体生成激素（LH），它们与相同的受体相互作用， 将被研究。 两种激素脉冲对孕酮的影响 在灌流系统中，黄体组织切片的分泌将被 检查以确定hCG是否诱导延长的类固醇生成反应， 在其他组织中看到。 由于已知hCG-LH受体复合物 在黄体细胞表面停留的时间是LH-LH受体的50倍 复合物，我们还将比较hCG LH受体的横向流动性 复合物和LH-LH受体复合物在黄体细胞膜上的表达 激光光漂白恢复技术 第二，最近的鉴定和 两种类型的类固醇黄体细胞的特征导致 实验设计为：1）鉴定起源于卵巢的黄体细胞类型， 从卵泡颗粒细胞和卵泡膜细胞; 2）表征细胞 在体内结合LH和PGF（2 α）的类型;和3）定义性质 细胞与细胞的相互作用导致黄体退化， 生殖周期或期间黄体的维持 怀孕 这些研究将使用体内和体外程序。 第三，由于黄体分泌孕酮似乎是 更多地依赖于LH受体的数量，而不是 这种激素在血液中的水平，涉及损失的机制， 将使用单克隆抗体研究LH受体的更新 和/或允许LH或hCG与LH受体结合的方法。 与受体共价连接。 最后，GTP结合的作用 蛋白质的激素激活腺苷酸环化酶将研究使用 GTP的光亲和类似物。 这些研究的结果将提供 新的信息，关于复杂的生物机制， 黄体分泌孕酮。