Modulation of Corticotropin Releasing Hormone Action

促肾上腺皮质激素释放激素作用的调节

• 批准号: 8718242
• 负责人: Gwen Childs
• 金额: $ 8万
• 依托单位: University of Texas Medical Branch at Galveston
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-15 至 1990-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8718242&HistoricalAwards=false
• 关键词: Modulation; Corticotropin; Releasing; Hormone; Action

This study will investigate basic mechanisms underlying cellular and subcellular responses of pituitary cells to corticotropin releasing hormone (CRH) and specific modulators of CRH action. It is focused on anterior lobe corticotropes and will study CRH binding and internalization (with quantitative electron microscopic cytochemical analyses) and hormone storage (with immunocytochemistry). The study will determine if inhibitors (glucocorticoids) or potentiators (vasopressin) of ACTH release alter the rate or route of CRH processing by corticotropes. The reserve cell population that is activated to bind CRH in the presence of the potentiator, vasopressin, will be identified. The study will test the hypothesis that potentiation of CRH action is dependent upon the activation of unique vasopressin sensitive cells that have the potential to produce ACTH. Another hypothesis that will be tested is that glucocorticoid inhibition of CRH action, in its early stages, includes either a block in the transport of CRH receptors to the plasma membrane or a rerouting of CRH-receptor complexes to lysosomes for rapid degradation. Changes in CRH binding will be identified with a biotinylated CRH ligand and labelled avidin stains. All cytochemical stains will be analyzed with the Bioquant System IV and image analysis system. The results of this research will enhance the understanding of basic mechanisms regulating the release of hormone by one type of pituitary cell, the corticotrope.

本研究将探讨基本的机制， 垂体细胞的细胞和亚细胞反应 促肾上腺皮质激素释放激素（CRH）和特异性调节剂 CRH行动。 它的重点是前叶促皮质激素， 将研究CRH结合和内化（定量 电子显微镜细胞化学分析）和激素储存 (with免疫细胞化学）。 该研究将确定， 抑制剂（糖皮质激素）或增效剂（加压素） 促肾上腺皮质激素释放改变CRH处理的速率或途径， 促皮质激素 储备细胞群被激活， 结合CRH的增效剂，加压素的存在下，将是 鉴定 这项研究将检验以下假设： CRH作用的增强依赖于 独特的加压素敏感细胞，有潜力， 产生ACTH。 另一个将被检验的假设是， 糖皮质激素抑制CRH作用，在其早期阶段， 包括阻断CRH受体转运至 质膜或CRH受体复合物的改道， 溶酶体的快速降解。 CRH绑定的变化将 用生物素化CRH配体和标记的抗生物素蛋白鉴定 渍. 所有细胞化学染色将使用 Bioquant System IV和图像分析系统。 这项研究的结果将增进对 调节激素释放的基本机制 脑垂体细胞，皮质激素。