The Corticotropin-Releasing Hormone Network and the Hypothalamic-Pituitary-Adrenal Axis: Molecular and Cellular Mechanisms Involved
The Corticotropin-Releasing Hormone Network and the Hypothalamic-Pituitary-Adrenal Axis: Molecular and Cellular Mechanisms Involved
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DOI：
10.1159/000328226
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发表时间：
2011-01-01
影响因子：
4.1
通讯作者：
Silberstein, Susana
中科院分区：
文献类型：
--
作者：
Jose Bonfiglio, Juan;Inda, Carolina;Silberstein, Susana
促肾上腺皮质激素释放激素（CRH）在调节基础和应激激活的下丘脑-垂体-肾上腺轴（HPA）中起关键作用。CRH也广泛分布于下丘脑外回路，作为神经调节剂整合复杂的神经内分泌、自主神经和行为适应应激反应。过度活跃和/或失调的CRH回路与神经内分泌紊乱和压力相关的情绪障碍（如焦虑和抑郁）有关。本文综述了CRH网络的主要生理特征，并对近年来利用细胞、野生型和转基因小鼠进行信号转导研究获得的CRH作用分子机制的相关信息进行了综述。特别关注CRH通过CRH受体1触发的MAPK信号通路，CRH受体1在垂体促肾上腺皮质激素和特定脑结构中的CRH作用中起重要作用。最近的研究结果支持了特定crh信号通路局限于特定解剖区域的概念。在分子水平上理解CRH的作用不仅可以提供CRH作用的确切机制，而且还将有助于确定参与CRH相关疾病的神经内分泌组织和特定脑区域的药物干预的新靶点。巴塞尔S. Karger股份有限公司版权所有
Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive response to stress. Hyperactive and/or dysregulated CRH circuits are involved in neuroendocrinological disturbances and stress-related mood disorders such as anxiety and depression. This review describes the main physiological features of the CRH network and summarizes recent relevant information concerning the molecular mechanism of CRH action obtained from signal transduction studies using cells and wild-type and transgenic mice lines. Special focus is placed on the MAPK signaling pathways triggered by CRH through the CRH receptor 1 that plays an essential role in CRH action in pituitary corticotrophs and in specific brain structures. Recent findings underpin the concept of specific CRH-signaling pathways restricted to specific anatomical areas. Understanding CRH action at molecular levels will not only provide insight into the precise CRH mechanism of action, but will also be instrumental in identifying novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. Copyright (C) 2011 S. Karger AG, Basel