CORTICOTROPIN RELEASING HORMONE BINDING PROTEIN

促肾上腺皮质激素释放激素结合蛋白

• 批准号: 6340146
• 负责人: AUDREY F. SEASHOLTZ
• 金额: $ 8.65万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-12-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6340146
• 关键词: DNA binding protein; DNA footprinting; animal tissue; cell type; corticosteroid receptors; corticotropin releasing factor; cyclic AMP; dexamethasone; fusion gene; gel electrophoresis; gene expression; genetic library; genetic mapping; genetic regulation; genetic regulatory element; genetic transcription; glucocorticoids; hormone regulation /control mechanism; human tissue; laboratory rat; neoplastic cell culture for noncancer research; nucleic acid sequence; protein purification; reporter genes; site directed mutagenesis; tissue /cell culture; transcription factor; transfection

DESCRIPTION (Adapted from the applicant's abstract): In light of the ability of CRH-BP to antagonize the biological activity of CRH in vitro, it is hypothesized that the CRH-BP modulates the actions of CRH in the pituitary and central nervous system. This hypothesis is tested by several independent approaches presented in this proposal. First, in situ hybridization histochemistry, immunocytochemistry, and RNase protection assays will be utilized to characterize the in vivo regulation of CRH-BP expression within the HPA axis during development and in response to glucocorticoids and stress, two important modulators of CRH expression and HPA activity. The expression and regulation of CRH-BP will also be examined in CRH-deficient mice. Second, the physiological consequences of increased level of CRH-BP in the anterior pituitary will be assessed in a transgenic mouse model of anterior pituitary CRH-BP overexpression. Third, the physiological consequences of decreased CRH-BP levels will be determined in a mammalian model of CRH-BP deficiency created by targeted mutation of the CRH-BP gene in embryonic stem cells. Together, these studies should allow the investigators to elucidate the physiological role of the CRH-BP in pituitary and brain. Finally, studies on the molecular characterization of CRH-BP gene regulation will be initiated in a number of CRH-BP expressing cell lines.

描述（改编自申请人的摘要）：鉴于 CRH-BP在体外具有拮抗CRH生物活性的能力， 假设 CRH-BP 调节 CRH 的作用 垂体和中枢神经系统。 这个假设被几个人验证 本提案中提出了独立的方法。 一、现场 杂交组织化学、免疫细胞化学和 RNase 保护 测定将用于表征 CRH-BP 的体内调节 发育过程中 HPA 轴内的表达以及响应 糖皮质激素和应激是 CRH 表达的两个重要调节因子 HPA 活性。 CRH-BP的表达和调节也将被检查 在 CRH 缺陷小鼠中。 二、增加的生理后果 垂体前叶的 CRH-BP 水平将在转基因中进行评估 垂体前叶CRH-BP过度表达的小鼠模型。 第三， CRH-BP 水平降低的生理后果将在 通过定向突变创建的 CRH-BP 缺陷哺乳动物模型 胚胎干细胞中的CRH-BP基因。 总之，这些研究应该允许 研究人员阐明了 CRH-BP 在 垂体和大脑。 最后，分子表征研究 CRH-BP基因调控将在许多CRH-BP表达中启动 细胞系。