The hypothalamic-pituitary-adrenal axis is frequently used as an example of a model system involving a negative-feedback control loop. In this model, a perceived decreased circulating or cellular concentration of glucocorticoids at the level of the hypothalamus or pituitary is followed by a release of corticotropin-releasing factor (CRF) and/or adrenocorticotropic hormone (ACTH) with subsequent stimulation of adrenal cortisol secretion. Conversely, elevated adrenal glucocorticoid secretion or exogenous glucocorticoid administration will decrease and subsequently suppress CRF and ACTH release. The site of glucocorticoid-induced CRF-ACTH suppression has not been definitively identified but is believed to involve loci in the cerebral cortex, hippocampus, amygdala, and other sites in the limbic system, as well as the hypothalamus and pituitary.1
See also p 2276.
A separate stress-sensitive pathway that stimulates ACTH and cortisol release is believed to bypass the classic negative-feedback loop, although the anatomic sites have not been delineated.2 Under certain conditions of severe