Corticotropin-releasing factor triggers neurite outgrowth of a catecholaminergic immortalized neuron via cAMP and MAP kinase signalling pathways

Eur J Neurosci. 2001 Apr;13(7):1339-48. doi: 10.1046/j.0953-816x.2001.01510.x.


Corticotropin-releasing factor (CRF), a neuropeptide of 41 amino acids, acts as the major physiological regulator of the basal and stress-induced release of corticotropin (ACTH), beta-endorphin and other proopiomelanocortin-derived peptides from the anterior pituitary gland. In addition to its endocrine activity, CRF displays extrahypophysiotropic effects, mainly as a regulator of stress responses. We show here that CRF may additionally function as a differentiating factor in immortalized noradrenergic neuronal CATH.a cells that express CRF receptor type I and resemble locus coeruleus-derived neurons. CRF triggers morphological changes in CATH.a cells including the appearance of extended long, slender neurites with prominent growth cones. CRF-treated CATH.a cells exhibit a morphology similar to locus coeruleus neurons in primary culture. CRF-induced neurite outgrowth of CATH.a cells was blocked by addition of inhibitors for cAMP-dependent protein kinase or extracellular signal-regulated protein kinase (ERK), a subtype of the mitogen-activated protein kinases. The participation of ERK within the CRF signalling cascade was further confirmed by Western blot experiments, with antibodies directed against the phosphorylated form of ERK, and also with transcription-based assays. We conclude that CRF functions as a differentiating factor of CATH.a cells via the cAMP and the MAP kinase signalling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Line, Transformed
  • Corticotropin-Releasing Hormone / pharmacology*
  • Cyclic AMP / metabolism*
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • DNA-Binding Proteins / genetics
  • Early Growth Response Protein 1
  • Female
  • Fetus / cytology
  • Fungal Proteins / genetics
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Immediate-Early Proteins*
  • Locus Coeruleus / cytology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • Neurites / drug effects*
  • Neurites / physiology
  • Neurons / enzymology*
  • Neurons / ultrastructure
  • Norepinephrine / genetics*
  • Norepinephrine / metabolism
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Pregnancy
  • Promoter Regions, Genetic / physiology
  • Proto-Oncogene Proteins*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Transcription Factors / genetics
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / physiology
  • ets-Domain Protein Elk-1


  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Fungal Proteins
  • GAL4 protein, S cerevisiae
  • Immediate-Early Proteins
  • Potassium Channels
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • Corticotropin-Releasing Hormone
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Norepinephrine