Circadian rhythms of melatonin, cortisol, and clock gene expression during simulated night shift work

Study Objectives: The synchronization of peripheral circadian oscillators in humans living on atypical sleep/wake schedules is largely unknown. In this night shift work simulation, we evaluate clock gene expression in peripheral blood mononuclear cells (PBMCs) relative to reliable markers of the central circadian pacemaker. Design: Participants were placed on a 10-hr delayed sleep/wake schedule simulating nighttime work followed by a daytime sleep episode. Setting: Baseline, intermediate and final circadian evaluations were performed in the temporal isolation laboratory. Participants: Five healthy candidates, 18-30 years. Interventions: Polychromatic white light of (mean +/- SEM) 6,036 +/- 326 lux (similar to 17,685 +/- 955 W/m(2)) during night shifts; dim light exposure after each night shift; an 8-hr sleep/darkness episode beginning 2 hrs after the end of each night shift. Measurements: Melatonin and cortisol in plasma-, clock genes HPER1, HPER2 and HBMAL1 RNA in PBMCs. Results: Following 9 days on the night schedule, hormonal rhythms were adapted to the shifted schedule. HPER1 and HPER2 expression in PBMCs displayed significant circadian rhythmicity, which was in a conventional relationship with the shifted sleep/wake schedule. Changes in the pattern of clock gene expression were apparent as of 3 days on the shifted sleep/wake schedule. Conclusions: This preliminary study is the first documentation of the effects of a shifted sleep/wake schedule on the circadian expression of both peripheral circadian oscillators in PBMCs and centrally-driven hormonal rhythms. In light of evidence associating clock gene expression with tissue function, the study of peripheral circadian oscillators has important implications for understanding medical disorders affecting night shift workers.