Glucocorticoids entrain molecular clock components in human peripheral cells

FASEB J. 2015 Apr;29(4):1360-70. doi: 10.1096/fj.14-265686. Epub 2014 Dec 12.


In humans, shift work induces a desynchronization between the circadian system and the outside world, which contributes to shift work-associated medical disorders. Using a simulated night shift experiment, we previously showed that 3 d of bright light at night fully synchronize the central clock to the inverted sleep schedule, whereas the peripheral clocks located in peripheral blood mononuclear cells (PBMCs) took longer to reset. This underlines the need for testing the effects of synchronizers on both the central and peripheral clocks. Glucocorticoids display circadian rhythms controlled by the central clock and are thought to act as synchronizers of rodent peripheral clocks. In the present study, we tested whether the human central and peripheral clocks were sensitive to exogenous glucocorticoids (Cortef) administered in the late afternoon. We showed that 20 mg Cortef taken orally acutely increased PER1 expression in PBMC peripheral clocks. After 6 d of Cortef administration, the phases of central markers were not affected, whereas those of PER2-3 and BMAL1 expression in PBMCs were shifted by ∼ 9.5-11.5 h. These results demonstrate, for the first time, that human peripheral clocks are entrained by glucocorticoids. Importantly, they suggest innovative interventions for shift workers and jet-lag travelers, combining synchronizing agents for the central and peripheral clocks.

Keywords: circadian; clock genes; cortisol; melatonin; shift work.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / blood
  • ARNTL Transcription Factors / genetics
  • Adult
  • Circadian Rhythm / drug effects*
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology
  • Double-Blind Method
  • Drug Administration Schedule
  • Gene Expression / drug effects
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / blood
  • Glucocorticoids / physiology
  • Humans
  • Hydrocortisone / administration & dosage*
  • Hydrocortisone / blood
  • Hydrocortisone / physiology
  • Jet Lag Syndrome / drug therapy
  • Jet Lag Syndrome / physiopathology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Melatonin / blood
  • Period Circadian Proteins / blood
  • Period Circadian Proteins / genetics
  • Sleep Disorders, Circadian Rhythm / drug therapy
  • Sleep Disorders, Circadian Rhythm / physiopathology
  • Young Adult


  • ARNTL Transcription Factors
  • ARNTL protein, human
  • Glucocorticoids
  • PER1 protein, human
  • PER2 protein, human
  • PER3 protein, human
  • Period Circadian Proteins
  • Melatonin
  • Hydrocortisone