title: CRH Receptor Signalling: Potential Roles in Pathophysiology.
abstract: To maintain homeostatic equilibrium, living organisms have evolved complex adaptation systems that control an array of behavioural, autonomic, neuroendocrine and immune responses. One of the important switches of this system is the hypothalamic hormone corticotropin-releasing hormone (CRH), which together with a family of related peptides (urocortins, UCNs) orchestrate stress-coping responses that reinstate homeostasis. Persistent disturbances in the homeostatic equilibrium either due to inadequate or persistently uncontrolled responses have been associated with pathogenic mechanisms of disease. CRH and UCNs exert their actions by activating two receptors of the Class B1 GPCRs, CRH-R1 and CRH-R2. Their signalling versatility allows activation of multiple and diverse signalling pathways characterized by 'cell-specific agonist-dependent signalling' responses. Alternative mRNA splicing, interactions with intracellular protein partners and mechanisms that allow selective regulation of signalling potency and termination, provide additional levels of regulation to fine-tune cellular responses. Although understanding of CRH-R signalling is still incomplete, recent important advances in decoding CRH-R structure and signalling properties uncovered key important functions and roles in physiology and pathobiology.
authors.affiliation: Division of Translational and Systems Medicine, Warwick Medical School, Clinical Sciences Research Institute, University Hospital Coventry and Warwickshire, Clifford Bridge Road, Coventry, P.O. Box: CV2 2DX. United Kingdom.
authors.forename: Dimitris K
authors.initials: DK
authors.lastname: Grammatopoulos
authors.affiliation: Division of Translational and Systems Medicine, Warwick Medical School, Clinical Sciences Research Institute, University Hospital Coventry and Warwickshire, Clifford Bridge Road, Coventry, P.O. Box: CV2 2DX. United Kingdom.
authors.forename: Styliani
authors.initials: S
authors.lastname: Ourailidou
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D060066:Protein Interaction Maps; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction
chemical_list: D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP
keywords: CRH; ERK1/2; GPCRs; Stress; cAMP; immune responses; intracellular
  protein; mRNA splicing; neuroendocrine; urocortins