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

Area of Science:

• Chronobiology
• Molecular Endocrinology

Background:

• Glucocorticoids (GCs) are recognized as internal timing signals for peripheral circadian oscillators.
• The precise transcription mechanisms of GC-related clock genes in peripheral tissues remain incompletely understood.

Purpose of the Study:

• To investigate the role of clock genes in GC-induced peripheral circadian gene expression in vivo.
• To explore how different GC administration schedules affect peripheral circadian rhythms.

Main Methods:

• Real-time RT-PCR was used to analyze transcript levels of clock genes (Per1, Dec1, Bmal1) in rat peripheral tissues (heart, kidney).
• Dexamethasone (Dex) was administered at different times (ZT0, ZT12) under normal light-dark (LD) and jet lag conditions.

Main Results:

• Per1 and Dec1 transcript levels were rapidly upregulated in the heart and kidney post-dexamethasone stimulation, suggesting they are primary and secondary responders.
• Circadian phases of Bmal1 and Per1 were significantly shifted by ZT0 Dex administration compared to ZT12, in both normal LD and jet lag conditions.
• ZT0 GC stimulation induced circadian disruption in normal LD cycles but may facilitate peripheral clock resetting under LD reversal.

Conclusions:

• Per1 and Dec1 are key early responders in GC-induced peripheral circadian gene expression.
• The timing of GC administration critically influences peripheral clock gene rhythms, with potential implications for circadian adaptation and disorder.