Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología y Biología Molecular y Celular, Universidad de Buenos Aires, Argentina.
Neuroendocrinology. 2011;94(1):12-20. doi: 10.1159/000328226. Epub 2011 May 13.
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.
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）方面发挥着关键作用。CRH 也广泛分布于下丘脑外回路中，作为一种神经调节剂，整合应激的复杂神经内分泌、自主和行为适应性反应。过度活跃和/或失调的 CRH 回路与神经内分泌紊乱和应激相关的情绪障碍有关，如焦虑和抑郁。这篇综述描述了 CRH 网络的主要生理特征，并总结了最近关于使用细胞和野生型和转基因小鼠系进行信号转导研究获得的 CRH 作用的分子机制的相关信息。特别关注的是 CRH 通过 CRH 受体 1 触发的 MAPK 信号通路，该通路在垂体促皮质素细胞和特定脑结构中 CRH 作用中发挥着重要作用。最近的发现支持了特定 CRH 信号通路仅限于特定解剖区域的概念。在分子水平上理解 CRH 的作用不仅将提供对 CRH 确切作用机制的深入了解，而且对于确定神经内分泌组织和与 CRH 相关疾病相关的特定脑区的药理学干预的新靶标也将具有重要意义。
