Schematic representation of the hypothalamic-pituitary-adrenal (HPA) axis. The initial changes in the axis in response to a stressful stimulus are shown in red. Stress increases CRH synthesis and release from neurons in the paraventricular nucleus (PVN) of the hypothalamus. CRH is carried to the anterior pituitary, where it binds to CRH receptors on corticotropes, resulting in increased synthesis of POMC and release of ACTH. ACTH, in turn, stimulates production of glucocorticoids from the adrenal cortex. Glucocorticoids signal for a variety of metabolic changes that allow the body to respond to the stressor. They also provide negative feedback (shown in red) at numerous levels in the HPA axis to terminate the stress response and maintain homeostasis.