CRH: The link between hormonal-, metabolic- and behavioral responses to stress

•Corticotropin-releasing hormone, CRH-41 has been discovered in 1981 by Wylie Wale and his colleagues.•Hypophyseotropic CRH has a pivotal role in initiating the neuroendocrine stress response.•Central CRH contributes to autonomic and behavioral stress response.•CRH gene is differentially regulated in the paraventricular nucleus and in the extended amygdala.

Two major and mutually interconnected brain systems are recruited during stress reaction. One is the hypothalamic paraventricular nucleus (PVH) and the second is the extended amygdala. PVH governs the neuroendocrine stress response while CeA regulates most of the autonomic and behavioral stress reactions. The common neurohormonal mediator of these responses is the corticotropin-releasing hormone, CRH, which is expressed in both centers. CRH belongs to a larger family of neuropeptides that also includes urocortins 1, 2, and 3 all have different affinity toward the two types of CRHR receptors and have been implicated in regulation of stress and HPA axis activity. One functionally relevant aspect of CRH systems is their differential regulation by glucocorticoids. While corticosterone inhibits CRH transcription in the PVH, stress-induced glucocorticoids stimulate CRH expression in the extended amygdala. This review summarizes past and recent findings related to CRH gene regulation and its involvement in the neuroendocrine, autonomic and behavioral stress reaction.