CORTICOTROPIN RELEASING HORMONE BINDING PROTEIN

描述(改编自申请人的摘要)：根据 CRH-BP体外拮抗CRH生物活性的研究 假设CRH-BP调节CRH在脑内的作用。 脑下垂体和中枢神经系统。这一假设得到了以下几个方面的检验 本提案中提出了独立的方法。第一，就地 杂交组织化学、免疫细胞化学和核糖核酸酶保护 实验将被用来表征CRH-BP的体内调节 在发育过程中HPA轴内的表达以及对 糖皮质激素和应激，CRH表达和应激的两个重要调节因子 HPA活动。此外，还将研究CRH-BP的表达和调控 在CRH缺陷小鼠中。第二，增加的生理后果 将通过转基因技术评估垂体前叶中CRH-BP的水平 小鼠垂体前叶CRH-BP过度表达模型。第三， CRH-BP水平下降的生理后果将在#年确定 靶基因突变所致CRH-BP缺乏症的哺乳动物模型 胚胎干细胞中的CRH-BP基因。总而言之，这些研究应该允许 研究人员试图阐明CRH-BP在心脏疾病中的生理作用 脑下垂体和大脑。最后，对其进行了分子表征研究。 CRH-BP基因调控将启动多个CRH-BP的表达 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.