Hormonal Regulation of Human Corticotropin-Releasing Hormone Gene Expression: Implications for the Stress Response and Immune/Inflammatory Reaction

EXPERIMENTAL support for the hypothesis that ACTH secretion is controlled by hypothalamic factors (1) was obtained in 1955 (2, 3). In 1981, a 41-amino acid C-terminal amidated peptide from ovine hypothalami stimulating pituitary ACTH release was identified in vitro and characterized (4). The biologically active form of this peptide, designated corticotropin-releasing hormone (CRH), and also frequently referred to as corticotropin-releasing factor (CRF), was synthesized and found to have potent ACTH-releasing actions in vivo (5). CRH is the only known permissive factor for the anterior pituitary release of ACTH in man (5, 6). It acts in synergy with arginine vasopressin (AVP) and, perhaps, other factors to regulate pituitary ACTH secretion and ultimately the activity of the pituitary-adrenal axis (7–9). Since its discovery, it has become evident that the role of CRH is much wider than initially thought. Coordination of the behavioral and physical components of the stress response and regulation of the immune/inflammatory reaction were shown to be major roles of this neuropeptide (10, 11).