CONTROL OF RELAXIN SECRETION FROM SINGLE LUTEAL CELLS

卵巢分泌类固醇激素和一系列蛋白质 激素对控制 生殖功能 然而，目前对这一点知之甚少。 调节卵巢释放的细胞和分子途径 蛋白质荷尔蒙 在这些拟议的研究中，一个更完整的 了解一种这样的激素，蛋白质激素松弛素， 将试图通过表征促分泌素， 有助于分泌功能的细胞内信号通路， 以及结构-功能关系的分析。 这些目标将通过使用反向溶血斑块来实现 比色法 该测定基于抗体导向的补体- 介导邻近激素分泌物的红细胞溶解，因此 使得能够在显微镜下观察 培养的单个黄体细胞。 的主要目标 建议的研究是：（a）评估的相对重要性， 和不同的反应，刺激性（异黄酮）， 松弛素抑制性（LH，自身抑制）促分泌素 释放;（B）表征影响、相互作用和 第二个问题的相对重要性和不同的反应 信使途径，如环核苷酸，钙 动员、蛋白激酶C激活和花生四烯酸 代谢物，并确定黄体细胞是否作为兴奋性 细胞;和（c）确定黄体的分泌特征 含有松弛素但不释放松弛素（“沉默”）的细胞 细胞”）。 为了实现这些目标， 将对单个分泌型乳腺癌患者进行监测， （在适当的情况下）与免疫细胞化学技术。 是 预计将获得有意义的信息， 细胞和分子的身份、重要性和相互作用 促进卵巢激素释放的机制。 此外，新 对非释放性分泌细胞之谜的深入了解， 获得。 这些知识最终不仅可以用来识别 卵巢病理的原因（和开发治疗方法）， 同时也是为了确定调节人类卵巢功能的新策略， 功能

The ovary secretes both steroid hormones and a spectrum of protein hormones that are of great importance to the control of reproductive function. However, little is presently known of the cellular and molecular pathways that regulate release of ovarian protein hormones. In these proposed studies, a more complete understanding of one such hormone, the protein hormone relaxin, will be attempted by characterizing the secretagogues and intracellular signalling pathways that subserve secretory function, together with an analysis of structure-function relationships. These objectives will be met by use of a reverse hemolytic plaque assay. This assay is based on antibody-directed, complement- mediated lysis of erythrocytes adjacent to hormone secretors, thus enabling the microscopic visualization of hormone release from individual luteal cells in culture. The primary objectives of the proposed studies are: (a) to evaluate the relative importance of, and differential response to, stimulatory (prostaglandins) and inhibitory (LH, auto-suppression) secretagogues for relaxin release; (b) to characterize the influence, interactions and relative importance of, and differential response to, second messenger pathways such as cyclic nucleotides, calcium mobilization, protein kinase C activation and arachidonic acid metabolites, and to determine if luteal cells function as excitable cells; and (c) to determine the secretory characteristics of luteal cells that contain relaxin but do not release relaxin ("silent" cells"). To accomplish these goals, the secretory characteristics of single hormone-secretors will be monitored, in combination (where appropriate) with immunocytochemical techniques. It is anticipated that meaningful information will be derived concerning the identity, importance and interactions of cellular and molecular mechanisms that subserve ovarian hormone release. Moreover, new insights into the enigma of non-releasing secretory cells will be gained. This knowledge can eventually be used not only to identify the causes of (and developing treatments for) ovarian pathologies, but also to identify new strategies for regulating human ovarian function.