Stress update Adaptation of the hypothalamic-pituitary-adrenal axis to chronic stress.

The hypothalamic-pituitary-adrenal (HPA) axis exhibits a circadian rhythm, activation by stress, and inhibition by corticosteroids. Activity in the HPA axis is very sensitive to inhibition by corticosteroids when they are administered exogenously. When stress-induced corticosteroid secretion occurs, however, normal activity in the HPA is not inhibited and may even be augmented. Experiments in rats have shown that stress also induces facilitation of subsequent activity in the HPA axis that appears to balance the inhibitory effects of corticosterone and thus maintains responsiveness to new, acute stresses in chronically stressed rats. Stress-induced facilitation of HPA axis activity may be mediated by a parallel stress-induced (CRH-dependent) increase in the capacity of brain noradrenergic cell groups to respond to acute stress. A continually responsive HPA axis, even under conditions of chronic stress, appears to be important for survival. Stress-induced increases in glucocorticoid secretion to levels sufficient to occupy glucocorticoid receptors enable appropriate thermoregulatory and cardiovascular responses to acute stress. There is, however, an overall metabolic cost to the animal of maintaining continued activity in the HPA axis during chronic stress.