Impaired adaptation to repeated restraint and decreased response to cold in urocortin 1 knockout mice

Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E259-63. doi: 10.1152/ajpendo.00616.2006. Epub 2007 Apr 24.


Urocortin 1 (UCN1) is a corticotropin-releasing factor (CRF)-like peptide whose role in stress is not well characterized. To study the physiological role of UCN1 in the response of the hypothalamic-pituitary-adrenal (HPA) axis to stress, we generated UCN1-knockout (KO) mice and examined their adaptation to repeated restraint and to cold environment. Wild-type (WT) and UCN1-KO animals were restrained hourly for 15 min from 9 AM to 2 PM, and blood samples were obtained for corticosterone measurement. WT animals adapted to repeated restraint with a decreased corticosterone response; the restraint-stimulated corticosterone levels fell from 215 +/- 31 ng/ml in naïve animals to 142 +/- 50 ng/ml in mice subjected to repeated restraint (P < 0.01) and from 552 +/- 98 to 314 +/- 58 ng/ml (P < 0.001) in males and females, respectively. Male UCN1-KO mice did not show any adaptation to repeated restraint; instead, restraint-stimulated corticosterone levels were increased from 274 +/- 80 ng/ml in naïve animals to 480 +/- 75 ng/ml in mice subjected to repeated restraint (P < 0.001). Female UCN1-KO mice showed only a partial adaptation to repeated restraint, with a decrease in the restraint-stimulated corticosterone response from 631 +/- 102 ng/ml in naïve animals to 467 +/- 78 ng/ml in mice subjected to repeated restraint (P < 0.01). In addition, UCN1-KO mice showed no corticosterone response to 2-h cold environment. These data demonstrate an important role for UCN1 in the HPA axis adaptation to repeated restraint and in the corticosterone response to a cold environment.

Publication types

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

MeSH terms

  • Adaptation, Physiological / genetics*
  • Animals
  • Cold Temperature*
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / genetics*
  • Female
  • Immobilization*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Restraint, Physical
  • Sex Characteristics
  • Stress, Psychological / blood
  • Stress, Psychological / genetics
  • Urocortins


  • Urocortins
  • Corticotropin-Releasing Hormone
  • Corticosterone