CORTICOTROPIN RELEASING HORMONE BINDING PROTEIN

描述（改编自申请人的摘要）：鉴于 CRH-BP体外拮抗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。 这一假设得到了几个人的检验。 本提案中提出的独立方法。 第一，在原地 杂交组织化学、免疫细胞化学和RNA酶保护 将使用测定来表征CRH-BP的体内调节 在HPA轴内的表达在发展过程中，并在响应 糖皮质激素和应激，CRH表达的两个重要调节剂， HPA活性。 CRH-BP的表达和调节也将被检查 在CRH缺陷小鼠中。 二是生理后果加重 将在转基因小鼠中评估垂体前叶中CRH-BP的水平。 垂体前叶CRH-BP过表达的小鼠模型。 三是 CRH-BP水平降低的生理后果将在 CRH-BP缺陷的哺乳动物模型通过CRH-BP基因的靶向突变产生， CRH-BP基因在胚胎干细胞中的表达 总之，这些研究应该允许 研究人员阐明CRH-BP的生理作用， 垂体和大脑。 最后，研究了 CRH-BP基因调控将在一些CRH-BP表达的细胞中启动， 细胞系

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.