Circadian and Glucocorticoid Regulation of Rev-erbα Expression in Liver¹

Treatment with dexamethasone resulted in a 70% decrease in Rev-erbalpha mRNA levels after 6 hours in rats.

• Rev-erbalpha is a nuclear receptor that represses gene transcription and is involved in myocyte differentiation and lipoprotein metabolism.
• The circadian rhythm of Rev-erbalpha expression is maintained in primary cultures of rat liver cells.
• Glucocorticoids, such as dexamethasone, significantly reduce Rev-erbalpha expression in a dose-dependent manner.
• The reduction in Rev-erbalpha mRNA levels by dexamethasone is mediated by the glucocorticoid receptor, as shown by the prevention of this effect with the antagonist RU486.
• Inhibition of protein synthesis increased Rev-erbalpha mRNA levels, but this increase was diminished by dexamethasone in both rat and human liver cells.
• Glucocorticoids appear to regulate Rev-erbalpha expression at the transcriptional level, as indicated by the effects of actinomycin D on repression.

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