The Molecular Physiology of CRH Neurons

Front Neuroendocrinol. 2012 Jan;33(1):67-84. doi: 10.1016/j.yfrne.2011.08.002. Epub 2011 Aug 18.


Corticotropin releasing hormone (CRH) is essential for stress adaptation by mediating hypothalamic-pituitary-adrenal (HPA) axis, behavioral and autonomic responses to stress. Activation of CRH neurons depends on neural afferents from the brain stem and limbic system, leading to sequential CRH release and synthesis. CRH transcription is required to restore mRNA and peptide levels, but termination of the response is essential to prevent pathology associated with chronic elevations of CRH and HPA axis activity. Inhibitory feedback mediated by glucocorticoids and intracellular production of the repressor, Inducible Cyclic AMP Early Repressor (ICER), limit the magnitude and duration of CRH neuronal activation. Induction of CRH transcription is mediated by the cyclic AMP/protein kinase A/cyclic AMP responsive element binding protein (CREB)-dependent pathways, and requires cyclic AMP-dependent nuclear translocation of the CREB co-activator, Transducer of Regulated CREB activity (TORC). This article reviews current knowledge on the mechanisms regulating CRH neuron activity.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Base Sequence
  • Corticotropin-Releasing Hormone / biosynthesis
  • Corticotropin-Releasing Hormone / physiology*
  • Cyclic AMP / physiology
  • Cyclic AMP Response Element Modulator / physiology
  • Cyclic AMP Response Element-Binding Protein / physiology
  • Cyclic AMP-Dependent Protein Kinases / physiology
  • Epigenesis, Genetic
  • Feedback
  • Glucocorticoids / physiology
  • Humans
  • Mice
  • Molecular Sequence Data
  • Neurons / physiology*
  • Paraventricular Hypothalamic Nucleus / growth & development
  • Rats
  • Signal Transduction / physiology
  • Stress, Physiological / physiology
  • Transcription Factors / physiology
  • Vasopressins / biosynthesis


  • Crem protein, rat
  • Crtc1 protein, rat
  • Cyclic AMP Response Element-Binding Protein
  • Glucocorticoids
  • Transcription Factors
  • Vasopressins
  • Cyclic AMP Response Element Modulator
  • Corticotropin-Releasing Hormone
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases