GCs are produced by the adrenal cortex in response to adrenocorticotropic hormone (ACTH) from the anterior pituitary. Corticotropin-releasing hormone (CRH), produced by cells in the hypothalamus, is the main stimulus of ACTH production. Hypothalamic CRH, in turn, is regulated by neurocircuits conveying day/night information (i.e., diurnal rhythm of the HPA system) and the state of the internal and external milieu (Herman and Cullinan, 1997; Herman et al., 2005; Herman et al., 2002). Stressors (actual or perceived threats) initiate a cascade beginning with hypothalamic CRH release, increased pituitary ACTH secretion, and adrenal production of GCs.
