Catecholaminergic Modulation of Corticotropin-Releasing Factor and Adrenocorticotropin Secretion

THE STABILITY of the “milieu interieur” was first recognized by Claude Bernard (1), and this concept was extended by Walter Cannon (2), who coined the term homeostasis to denote the condition of relative constancy of the internal environment. The hypothalamic-pituitary-adrenal axis (HPA) and the autonomic nervous system are recognized as primary effector systems which serve to minimize excursions from the homeostatic state and to restore a relative equilibrium in response to disturbances (3, 4). Many of the physiological adjustments accompanying sympathetic activation complement those brought about by glucocorticoid secretion. Indeed, the responsiveness and physiological consequences of activation of these two systems are so inter-twined as to have generated the hypothesis that activation of the HPA is evoked by sympathoadrenomedullary activation (5, 6). Thus an organism's response to an actual or perceived challenge (stressor) usually involves activation of both the HPA and the sympathetic-adrenomedullary system (7–9). Interest in the central neurochemical regulation of the HPA and autonomic nervous system focused upon the catecholamines with the demonstration that norepinephrine (NE) was present within neurons of the brain (10). The possibility that central catecholamines might modulate HPA function (11–15) received morphological support after the mapping of central catecholaminergic projections (16–21).