Glucocorticoids entrain molecular clock components in human peripheral cells.

🎖️ Top 10% JournalDec 16, 2014FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Glucocorticoids set the timing of molecular clocks in human body cells

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Abstract

Oral administration of 20 mg Cortef acutely increased PER1 expression in peripheral blood mononuclear cells (PBMCs).

Glucocorticoids may synchronize human peripheral clocks, as indicated by changes in gene expression.
After 6 days of Cortef administration, the phases of certain markers in PBMCs shifted by approximately 9.5-11.5 hours.
The central clock markers remained unaffected by glucocorticoid treatment during the study period.
These findings suggest that interventions combining synchronizing agents could benefit shift workers and travelers dealing with jet lag.

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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.

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