Stress stimulates release of corticotropin-releasing factor (CRF) from the hypothalamus. CRF binds to receptors on the anterior pituitary gland, stimulating the release of adrenocorticotropic hormone (ACTH). ACTH then binds to receptors in the adrenal cortex to stimulate adrenal release of cortisol. This release of cortisol occurs several hours after the initial exposure to the stressor. One the blood concentration of cortisol reaches a certain level, cortisol exerts negative feedback on the hypothalamic release of CRF and pituitary release of ACTH, returning the body to homeostasis. However, as we age, this negative feedback mechanism becomes less effective, causing higher levels of cortisol secretion into the blood.