Regulation of hypoxia-induced release of corticotropin-releasing factor in the rat hypothalamus by norepinephrine

Regul Pept. 2004 Jul 15;119(3):221-8. doi: 10.1016/j.regpep.2004.02.005.


Corticotropin-releasing factor (CRF) peptide release was activated by hypoxia in the rat hypothalamus. The mechanisms, however, of the hypoxia-induced CRF release remains unclear. In this study, we demonstrated that the norepinephrine (NE) and its receptors in the paraventricular nucleus (PVN) mediated the CRF release in a simulated altitude hypoxia. When rats were exposed to 5 or 7 km altitude of hypoxia for a short or long term: (1) NE levels in the PVN and the CeA, using the HPLC analysis, were intensity and time course dependently increased, but the increase in the PVN were potential than in the CeA. Restraint-induced NE increase was much higher in both the PVN and the CeA, compared with hypoxia-induced response. (2) Hypoxia and restraint significantly enhanced CRF release in the ME and the PVN but not in the CeA, through RIA assay, which result in stimulating corticosterone secretion. (3) Hypoxia-induced CRF release was reversed by an injection of prazosin (i.c.v.), an alpha-1 adrenoceptor antagonist, while administration of yohimbine (i.c.v.), an alpha-2 receptor antagonist, facilitated further CRF release. These data suggested that hypoxia induced NE activation centrally, via alpha-1 and -2 receptors, leading to improving hypothalamic CRF release, which in turn stimulated pituitary and adrenal cortex. Restraint presented much potential action on NE activation than hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / administration & dosage
  • Amygdala / physiopathology*
  • Animals
  • Corticotropin-Releasing Hormone / metabolism*
  • Hypoxia, Brain / physiopathology*
  • Male
  • Norepinephrine / metabolism*
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Paraventricular Hypothalamic Nucleus / physiopathology*
  • Prazosin / administration & dosage
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic / metabolism*
  • Restraint, Physical


  • Adrenergic alpha-Antagonists
  • Receptors, Adrenergic
  • Corticotropin-Releasing Hormone
  • Norepinephrine
  • Prazosin