CRHBP's role in mediating HPA/HPG interactions

CRHBP 在介导 HPA/HPG 相互作用中的作用

• 批准号: 7022324
• 负责人: NICOLE J WESTPHAL
• 金额: $ 2.95万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7022324
• 关键词: SDS polyacrylamide gel electrophoresis; adrenocorticotropic hormone; binding proteins; biological signal transduction; corticotropin releasing factor; crosslink; genetic regulation; genetically modified animals; glycoproteins; gonadotropins; hormone receptor; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; hypothalamic pituitary axis; laboratory mouse; pituitary gonadal axis; polymerase chain reaction; predoctoral investigator; protein structure function; site directed mutagenesis; tissue /cell culture; western blottings

DESCRIPTION (provided by applicant): Physical and psychological stress are known to activate the hypothalamic-pituitary-adrenal (HPA) axis; however, stress has also been shown to negatively impact the HP-gonadal (HPG) axis. Studies have demonstrated that Corticotropin-Releasing Hormone (CRH), the key hypophysiotrophic effector molecule of the HPA axis, plays a significant role in stress-induced inhibition of reproduction. While CRH is known to act centrally, regulation may exist at the pituitary. CRH binds two receptors and a CRH binding protein (CRHBP), a 37kD glycoprotein thought to be an important modulator of CRH activity. Both CRH-receptors and CRHBP have recently been localized to murine gonadotrope, the primary pituitary cell type involved in reproductive signaling. This localization and the dramatic GnRH-induced increases in CRHBP expression in gonadotrope-like cells suggest that the gonadotrope should be reexamined as a potential site for HPA/HPG interactions and that CRHBP may play an important role in modulating these interactions. This proposal will examine GnRH regulation of endogenous CRHBP expression, molecular mechanisms mediating GnRH induced CRHBP gene regulation, and CRHBP modulation of CRH/HPG interactions in gonadotrope. An understanding of how reproductive hormones regulate CRHBP expression and how CRHBP modulates CRH activity will be important for our understanding of diseases involving CRH dysregulation, including deoression anorexia, anxiety and reproductive disorders.

描述(申请人提供)：众所周知，生理和心理压力会激活下丘脑-垂体-肾上腺(HPA)轴；然而，压力也被证明对HP-性腺(HPG)轴有负面影响。研究表明，促肾上腺皮质激素释放激素(CRH)是HPA轴的关键促垂体素效应分子，在应激诱导的生殖抑制中发挥重要作用。虽然已知CRH起中枢作用，但调节可能存在于脑下垂体。CRH结合两个受体和一个CRH结合蛋白(CRHBP)，CRHBP是一种37kD的糖蛋白，被认为是CRH活性的重要调节因子。CRH受体和CRHBP最近都被定位于小鼠促性腺激素，促性腺激素是参与生殖信号的主要垂体细胞类型。这种定位和GnRH诱导的CRHBP在促性腺激素样细胞中的表达显著增加，表明促性腺激素应该被重新研究为HPA/HPG相互作用的潜在部位，CRHBP可能在调节这些相互作用中发挥重要作用。该方案将研究GnRH对内源性CRHBP表达的调节，GnRH诱导CRHBP基因调节的分子机制，以及CRHBP对促性腺激素CRH/HPG相互作用的调节。了解生殖激素如何调节CRHBP的表达，以及CRHBP如何调节CRH的活性，对于我们理解与CRH失调相关的疾病，包括退行性厌食、焦虑和生殖障碍，将是非常重要的。