Insights into mechanisms of corticotropin-releasing hormone receptor signal transduction

Br J Pharmacol. 2012 May;166(1):85-97. doi: 10.1111/j.1476-5381.2011.01631.x.


During evolution, mammals have developed remarkably similar molecular mechanisms to respond to external challenges and maintain survival. Critical regulators of these mechanisms are the family of 'stress'-peptides that consists of the corticotropin-releasing hormone (CRH) and urocortins (Ucns). These neuropeptides 'fine-tune' integration of an intricate series of physiological responses involving the autonomic, endocrine, immune, cardiovascular and reproductive systems, which induce a spectrum of behavioural and homeostatic changes. CRH and Ucns exert their actions by activating two types of CRH receptors (CRH-R), CRH-R1 and CRH-R2, which belong to the class-B1 family of GPCRs. The CRH-Rs exhibit signalling promiscuity facilitated by their ability to couple to multiple G-proteins and regulate diverse intracellular networks that involve intracellular effectors such as cAMP and an array of PKs in an agonist and tissue-specific manner, a property that allows them to exert unique roles in the integration of homeostatic mechanisms. We only now begin to unravel the plethora of CRH-R biological actions and the transcriptional and post-translational mechanisms such as alternative mRNA splicing or phosphorylation-mediated desensitization developed to tightly control CRH-Rs biological activity and regulate their physiological actions. This review summarizes the current understanding of CRH-R signalling complexity and regulatory mechanisms that underpin cellular responses to CRH and Ucns.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing
  • Animals
  • Corticotropin-Releasing Hormone / metabolism*
  • Cyclic AMP / metabolism
  • Humans
  • Phosphorylation
  • RNA, Messenger / metabolism
  • Receptors, Corticotropin-Releasing Hormone / metabolism*
  • Signal Transduction / physiology
  • Urocortins / metabolism*


  • CRF receptor type 2
  • RNA, Messenger
  • Receptors, Corticotropin-Releasing Hormone
  • Urocortins
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone
  • Cyclic AMP