Glucocorticoid feedback resistance

Glucocorticoid feedback resistance can be inherited or locally acquired. The implications of these two forms of resistance for disease are strikingly different. The inherited form is characterized by enhanced adrenocortical function and hypercorticism to compensate for a generalized deficit in the glucocorticoid receptor gene, but these individuals lack symptoms of Cushing's syndrome. By contrast, resistance acquired at the level of the hypothalamic corticotropin-releasing hormone (CRH) neurons is linked to hypercorticism, which is not compensatory but overexposes the rest of the body and the brain to glucocorticoids. This cell-specific glucocorticoid resistance can be acquired by genetically predisposed individuals failing to cope with (early) life events and causes enhanced vulnerability to disease-specific actions of glucocorticoids. (C) 1997, Elsevier Science Inc.