A fundamental issue in the neurobiology of adaptation disorders is how the hormones of the hypothalamic-pituitary-adrenal (HPA) axis protect the brain from such disorders, and how in a different context these very same stress hormones may enhance vulnerability. This contribution focuses on the corticosteroids which exert through two distinct nuclear receptor types control over gene networks underlying stress system activity in brain. The mineralocorticoid receptor mediates the pro-active mode of corticosteroid action involved in maintenance of basal stress system activity. The glucocorticoid receptor mediates the reactive feedback mode aimed to facilitate recovery from stress-induced disturbance. The balance between these pro-active and reactive modes of control is thought to be of critical importance for homeostasis, and thus for control of hormone-responsive genes which enhance vulnerability to stress-related affective and neurodegenerative disorders.
