Short term activation of the stress-response system, a major element of which is the hypothalamic–pituitary–adrenal (HPA) axis, is essential for survival. In response to acute stress, hypothalamic corticotropin releasing hormone (CRH) stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary which in turn stimulates the release of the glucocorticoid hormone cortisol from the adrenal cortex. Cortisol binding to the glucorticoid receptor (GR) and the translocation of the GR from the cytoplasm into the nucleus in order to facilitate transcription of stress-response genes is moderated by a large molecular complex that includes FKBP5, a co-chaperone of hsp90 (Binder, 2009). The availability of CRH is regulated in part by a high-affinity binding protein (CRHBP) that is widely distributed throughout the body (Westphal and Seasholtz, 2006). A large proportion of total CRH is complexed with CRHBP and is therefore unavailable for receptor (CRHR1, CRHR2) activation (Behan et al., 1997).
