Time-dependent glucocorticoid administration differently affects peripheral circadian rhythm in rats

Abstract

There is a growing recognition that glucocorticoid (GC) acts as an internal timing signal for peripheral circadian oscillators. However, the transcription process of GC-related clock gene in the peripheral tissues is not fully understood. The present study was designed to explore the potential role of clock genes in the GC-induced peripheral circadian gene expression invivo. Real-time RT-PCR analysis indicated that the transcript levels of Per1 and Dec1 were rapidly up-regulated within 0.5 and 1 h in the heart and kidney respectively after stimulation with dexamethasone (Dex). These results suggest that Per1 and Dec1 serve as the primary and secondary responsers respectively in initiating the GC-induced peripheral circadian gene expression. By comparing the effects of the different GC administration schedules on the circadian rhythm of clock genes in peripheral tissues in rats, we found that the circadian phases of Bmal1 and Per1 were shifted more in the ZT0 (endogenous valley time) Dex stimulation group than in the ZT12 (endogenous peak time) Dex stimulation group in heart and kidney under the normal LD cycle. Under the jet lag condition, the circadian phases of Bmal1 and Per1 were also shifted more in the ZT0 Dex stimulation group than in the ZT12 Dex stimulation group. Therefore, the GC stimulation in the endogenous valley time caused circadian disorder in the normal LD cycle, but it might benefit the circadian resetting of peripheral clocks under the LD reversal condition.

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