Circadian and Glucocorticoid Regulation of Rev-erbα Expression in Liver1

Rev-erbα [NR1D1], a member of the nuclear receptor superfamily, is an orphan receptor that constitutively represses gene transcription. Rev-erbα has been shown to play a role in myocyte differentiation and to be induced during adipogenesis. Furthermore, Rev-erbα is a regulator of lipoprotein metabolism. It was recently shown that Rev-erbα messenger RNA (mRNA) levels oscillate diurnally in rat liver. Here, we report that the circadian rhythm of Rev-erbα in liver is maintained in primary cultures of rat hepatocytes. Because glucocorticoids have been shown to regulate other transcription factors with circadian expression, it was furthermore examined whether hepatic Rev-erbα expression is also regulated by glucocorticoids. Treatment of rats with dexamethasone resulted in a decrease of Rev-erbα mRNA levels by 70% after 6 h. Furthermore, dexamethasone decreased Rev-erbα expression in rat primary hepatocytes in a dose-dependent fashion. This effect was mediated by the glucocorticoid receptor because simultaneous...