STRUCTURAL STUDIES OF RECEPTORS FOR LACTOGENIC HORMONES

催乳激素受体的结构研究

• 批准号: 3325358
• 负责人: Luis S Haro
• 金额: $ 8.08万
• 依托单位: WHITTIER INSTITUTE FOR DIABETES & ENDOC
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3325358
• 关键词: antiserum; crosslink; gel electrophoresis; gestational age; growth /development; high performance liquid chromatography; hormone receptor; hormone regulation /control mechanism; immunochemistry; laboratory mouse; laboratory rabbit; mammalian embryology; mammary gland; membrane proteins; prolactin; protein sequence; proteolysis; radiotracer; somatomammotropin; tissue /cell culture

During pregnancy, the lactogenic hormones prolactin and placental lactogen participate in the regulation of processes such as mammary gland differentiation, steroidogenesis, somatic growth and intermediary metabolism in a variety of animals. Regulation of these processes is achieved through fluctuations in the levels of the lactogenic hormones. We know that lactogenic hormones are structurally similar and possess overlapping biological activities, but very little is known about their receptors. It is not known whether these hormones send a biochemical signal through a receptor unique to each hormone or, alternatively, whether they function through a common receptor. Since the lactogenic hormones influence a variety of biological processes, it is important to have knowledge about receptors for each specific lactogen over the course of pregnancy. The mouse will be used as a biological model to study lactogenic receptors over the course of gestation. A prolactin receptor will be isolated from mouse mammary glands. The purified receptor will be structurally analyzed by peptide mapping, amino acid analysis, N-terminal analysis, and other biochemical means. An antiserum will be generated with purified prolactin receptor and employed as an immunochemical probe. After crosslinking radiolabelled lactogens to receptors from organs removed on different days of gestation, hormone- receptor complexes will be analyzed by two-dimensional polyacrylamide gel electrophoresis, immunoblotting and autoradiography for determination of the multiplicity of lactogenic receptors. Electroimmunochemical techniques will be used to ascertain structural similarities that exist among prolactin receptors of different target organs. Ontogeny of lactogenic receptors during pregnancy in both the mother and fetus will be monitored by electrophoresis and immunostaining of receptors from several tissues. The potency and specificity of the interaction of glycosylated prolactin with receptors will be examined using radioreceptorassays, crosslinking and immunochemical methodologies. These studies should provide information that will improve our understanding about receptors for lactogenic hormones in the mouse, and perhaps will lead to an understanding about receptors for human lactogenic hormones.

在怀孕期间，催乳激素和 胎盘催乳素参与调节过程， 如乳腺分化、类固醇生成、体细胞 生长和中间代谢在各种动物。 这些过程的调节是通过 催乳激素的水平 我们知道催乳素 激素在结构上相似， 生物活性，但很少有人知道他们的 受体。 目前尚不清楚这些激素是否会 生物化学信号通过每种激素特有的受体， 或者，它们是否通过共同的受体发挥作用。 由于催乳激素影响多种生物学特性， 过程中，重要的是要了解受体， 在怀孕过程中每种特定的催乳素。 鼠标 将被用作研究催乳素受体的生物模型 在妊娠过程中。 从小鼠乳腺中分离出一种催乳素受体， 腺体 纯化的受体将进行结构分析， 肽图谱，氨基酸分析，N-末端分析，和 其他生化手段。 将用以下物质生成抗血清： 纯化的催乳素受体并用作免疫化学 探针 将放射性标记的催乳素与受体交联后 在不同的妊娠期取出的器官，激素- 受体复合物将通过二维分析 聚丙烯酰胺凝胶电泳，免疫印迹和 放射自显影法测定多重性 催乳素受体 电免疫化学技术将是 用于确定存在于 不同靶器官的催乳素受体。 的个体发育 催乳素受体在怀孕期间在母亲和 将通过电泳和免疫染色监测胎儿， 几种组织的受体。 的效力和特异性， 糖基化催乳素与受体的相互作用将是 使用放射性受体测定、交联和 免疫化学方法。 这些研究应该提供的信息，将改善我们的 了解催乳激素的受体， 也许会让我们对感受器有更深的了解 人类催乳激素的研究