Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice

J Clin Invest. 1997 Jun 15;99(12):2923-9. doi: 10.1172/JCI119487.


The normal pattern of daily glucocorticoid production in mammals requires circadian modulation of hypothalamicpituitary-adrenal axis activity. To assess both the factors responsible for imparting this diurnal profile and its physiologic importance, we have exploited corticotropin-releasing hormone (CRH)-deficient mice generated by homologous recombination in embryonic stem cells. CRH-deficient mice have lost normal circadian variations in plasma ACTH and glucocorticoid while maintaining normal circadian locomotor activity. Constant peripheral infusion of CRH produced marked diurnal excursions of plasma glucocorticoid, indicating that CRH acts in part as a permissive factor for other circadian modulators of adrenocortical activity. The presence of atrophic adrenals in CRH-deficient mice without an overt deficit in basal plasma ACTH concentration suggests that the diurnal increase in ACTH is essential to maintain normal adrenal function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Cortex / physiology
  • Adrenocorticotropic Hormone / blood
  • Animals
  • Blood Glucose / metabolism
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology*
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / deficiency*
  • Corticotropin-Releasing Hormone / pharmacology*
  • Female
  • Glucocorticoids / blood
  • Insulin / blood
  • Light
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / physiology
  • Photoperiod


  • Blood Glucose
  • Glucocorticoids
  • Insulin
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Corticosterone