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

Abstract

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.

Keywords: ADX; BAT; Bed nucleus of stria terminalis; CNS; CREB; CRH; Central amygdala; Corticosterone; Corticotropin-releasing hormone; DAG; GR; LC; LTP; PVH; Paraventricular nucleus; SNS; TORC; adrenalectomy; brown adipose tissue; cAMP; cAMP response element binding protein; cAMP-response element; central nervous system; corticotropin-releasing hormone; cyclic AMP; diacylglycerol; dorsal parvocellular subdivision of PVH; dp; glucocorticoid receptor; icv; intracerebroventricular (injection); lateral parvocellular subdivision of PVH; locus coeruleus; long term potentiation; lp; medial parvocellular dorsal subdivision of PVH; medial parvocellular ventral subdivision of PVH; mpd; mpv; paraventricular nucleus of the hypothalamus; sympathetic nervous system; transducer of regulated CREB activity.