Brain corticotropin releasing hormone and stress reactivity

The hypothalamic-pituitary-adrenocortical axis is one of the main components of stress adaptation. Corticotropin-releasing hormone (CRH) coming from the nucleus paraventricularis hypothalami (PVN) is the canonical central regulator of the axis. This CRH acts on the CRH-R1 receptors of the pituitary, and, through adrenocorticotropin, stimulates glucocorticoid release from the adrenal cortex. However, it may be synthetized in other parts of the brain as well, and may act both on CRH-R1 and CRH-R2 receptors. These areas form the central CRH network. Many of them are also stress reactive and participate in physical and psychological stress response. The central nucleus of the amygdala and bed nucleus of stria terminalis are two areas best known for their role in emotions, while hippocampus is mostly involved in glucocorticoid feedback as well as memory formation, all heavily connected to stress adaptation. Among others, the brainstem raphe nuclei get dense CRHergic innervation that, through CRH-R1 receptors, may influence the serotoninergic tone of the brain. Both stress and serotonin are strongly implicated in depression, therefore, it is not surprising that CRH-R1 antagonists were developed as therapeutic tools that extensively act on the brain CRH system. Our review suggests a general role of brain CRH network in stress adaptation which is not restricted to PVN.