THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS RESPONSE TO STRESS

The hypothalamic-pituitary-adrenal (HPA) axis is a central neuroendocrine system involved in the physiological response to stress and the maintenance of homeostasis. Exposure to physical or psychological stressors activates corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) secretion from the hypothalamic paraventricular nucleus, followed by adrenocorticotropic hormone (ACTH) release from the anterior pituitary and cortisol synthesis in the adrenal cortex. Cortisol supports short-term adaptation by mobilizing energy substrates, modifying immune activity, and maintaining cardiovascular responsiveness. The activity of the HPA axis is normally constrained by glucocorticoid- and mineralocorticoid-receptor-mediated negative feedback at the hippocampus, hypothalamus, and pituitary gland. When stress becomes prolonged, persistent activation of this system may impair feedback regulation and contribute to allostatic load. Chronic HPA-axis dysregulation has been associated with metabolic, cardiovascular, immune, and psychiatric disturbances. This review summarizes the structural organization and activation of the HPA axis, the major physiological actions of cortisol, mechanisms of negative feedback, and the pathophysiological consequences of chronic stress.