GLUCOCORTICOID FEEDBACK RESISTANCE

Glucocorticoid feedback resistance can be inherited or locally acquire d. The implications of these two forms of resistance for disease are s trikingly different. The inherited form is characterized by enhanced a drenocortical function and hypercorticism to compensate for a generali zed 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 o verexposes the rest of the body and the brain to glucocorticoids. This cell-specific glucocorticoid resistance can be acquired by geneticall y predisposed individuals failing to cope with (early) life events and causes enhanced vulnerability to disease-specific actions of glucocor ticoids. (C) 1997, Elsevier Science Inc.