Functional characteristics of CRH receptors and potential clinical applications of CRH-receptor antagonists.

Corticotropin-releasing hormone (CRH) plays a major role in coordinating the behavioral, endocrine, autonomic and immune responses to stress. CRH and CRH-related peptides and their receptors are present in the central nervous system and in a wide variety of peripheral tissues, including the immune, cardiovascular and reproductive systems, and have been associated with the pathophysiology of many disease states. These observations have led to the development of several CRH receptor type-selective antagonists, which have been used experimentally to elucidate the role of CRH and related peptides in physiological and disease processes, such as anxiety and depression, sleep disorders, addictive behavior, inflammatory and allergic disorders, neurological diseases and pre-term labor. Because of the complex network of multiple CRH receptor subtypes and their tissue- and agonist-specific signaling diversity, antagonists need to be developed that can target specific CRH receptor isoform-driven signaling pathways.