Region-specific roles of the corticotropin-releasing factor-urocortin system in stress

Nat Rev Neurosci. 2016 Oct;17(10):636-51. doi: 10.1038/nrn.2016.94. Epub 2016 Sep 2.


Dysregulation of the corticotropin-releasing factor (CRF)-urocortin (UCN) system has been implicated in stress-related psychopathologies such as depression and anxiety. It has been proposed that CRF-CRF receptor type 1 (CRFR1) signalling promotes the stress response and anxiety-like behaviour, whereas UCNs and CRFR2 activation mediate stress recovery and the restoration of homeostasis. Recent findings, however, provide clear evidence that this view is overly simplistic. Instead, a more complex picture has emerged that suggests that there are brain region- and cell type-specific effects of CRFR signalling that are influenced by the individual's prior experience and that shape molecular, cellular and ultimately behavioural responses to stressful challenges.

Publication types

  • Review

MeSH terms

  • Animals
  • Anxiety / physiopathology*
  • Corticotropin-Releasing Hormone / physiology*
  • Depression / physiopathology*
  • Humans
  • Models, Neurological
  • Receptors, Corticotropin-Releasing Hormone / physiology*
  • Stress, Psychological / physiopathology*
  • Urocortins / physiology*


  • Receptors, Corticotropin-Releasing Hormone
  • Urocortins
  • Corticotropin-Releasing Hormone