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ABSTRACT
Colonic function is controlled by an endogenous clock that allows the colon to optimize its function on the daytime basis. For the first time, this study provided evidence that the clock is synchronized by rhythmic hormonal signals. In rat colon, adrenalectomy decreased and repeated applications of dexamethasone selectively rescued circadian rhythm in the expression of the clock gene Per1. Dexamethasone entrained the colonic clock in explants from mPer2Luc mice in vitro. In contrast, pinealectomy had no effect on the rat colonic clock, and repeated melatonin injections were not able to rescue the clock in animals maintained in constant light. Additionally, melatonin did not entrain the clock in colonic explants from mPer2Luc mice in vitro. However, melatonin affected rhythmic regulation of Nr1d1 gene expression in vivo. The findings provide novel insight into possible beneficial effects of glucocorticoids in the treatment of digestive tract-related diseases, greatly exceeding their anti-inflammatory action.
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Acknowledgments
We thank Matus Sotak, PhD, Martin Vodicka, Pavlina Kvapilova, Eva Suchanova and Lucie Heppnerova for their excellent technical help.
Declaration of interest
The authors declare no conflict of interest.
Funding
The part of the study on the role of melatonin in the colonic clock was supported by the Czech Science Foundation (grant number 14-07711S, to Alena Sumová), and the study on the role of glucocorticoids was supported by the Czech Science Foundation (grant number 13-08304S, to Jiří Pácha). The study was also supported by Research Project RV0: 67985823.