Corticotrophin releasing hormone (CRH), a 41-amino acid peptide, is the main regulator of pituitary adrenocorticotrophic hormone (ACTH). Its secretion in humans plays a major role in the physiologic response to stress. CRH Type 1 and 2 receptors are widely distributed throughout the CNS and to a lesser extent in peripheral tissues. The CRH neurones modulate autonomic (locus ceruleus) and limbic system function. Furthermore, the presence of CRH receptors in inflammatory tissue and the placenta suggests that this neuropeptide is involved in modulation of the immune response and parturition. Hypersecretion of CRH is thought to play a pivotal role in the pathophysiology of major depression, anxiety and drug withdrawal. Therefore, antagonising CRH action has become a major therapeutic strategy for these disorders. Data from transgenic mice lacking or overexpressing CRH and preclinical studies with CRH antagonists have supported this theory. The development of a soluble, highly lipophilic and selective non-peptide CRH receptor (Type 1) antagonist remains a challenge. Elucidation of the role of the CRH Type 2 receptor will provide further insight into the specific role of this peptide in the periphery and selected areas of the CNS.
- Corticotrophin releasing hormone
ASJC Scopus subject areas
- Medicine (miscellaneous)