adrenocorticotropic hormone (ədrēˈnōkôrˌtəkōtrŏpˈĭk) [key], polypeptide hormone secreted by the anterior pituitary gland. Its chief function is to stimulate the cortex of the adrenal gland to secrete adrenocortical steroids, chief among them cortisone. The release of adrenocorticotropic hormone (ACTH), also known as corticotropin, is stimulated by corticotropin-releasing factor (CRF), a secretion of the hypothalamus. ACTH secretion is an excellent example of the regulation of a biological system by a negative-feedback mechanism; high levels of adrenocortical steroids in the blood tend to decrease ACTH release, whereas low steroid levels have the opposite effect. ACTH has the same pharmacologic and clinical effects as cortisone when given intravenously or intramuscularly; however, it has no value when applied externally and cannot be taken orally since it is deactivated by digestive enzymes. The action of ACTH is contingent upon normally functioning adrenal glands and is therefore useless in disorders caused by adrenal insufficiency, e.g., as replacement therapy where both adrenal glands have been removed.