Fig. 1.

Physiology of the HPA axis. Cortisol secretion is rigorously controlled by the HPA axis, which works with a tethering mechanism of negative feedback at all levels. Stress stimulates the hypothalamus to increase the secretion of CRH, a hormone that stimulates specialized cells of the anterior pituitary gland to release ACTH. ACTH reaches the adrenal cortex and stimulates the production of steroids, such as cortisol. Cortisol contributes to the restoration and maintenance of haemostasis during stress, counteracts many steps of the inflammatory response, stimulates gluconeogenesis and glycogenolysis, and maintains vascular tone and endothelial integrity. ACTH, adrenocorticotrophic hormone; CRH, corticotropin-releasing hormone; HPA, hypothalamic-pituitary-adrenal.