Circadian and Glucocorticoid Regulation of Rev-erbα Expression in Liver 1

作者：Inès Pineda‐Torra, Vladimir P. Tsibulsky, Franck Delaunay, Régis Saladin, Vincent Laudet, Jean‐Charles Fruchart, V. P. Kosykh, Bart Staels · 发表于：Endocrinology · 年份：2000 · DOI：10.1210/endo.141.10.7708 · 被引用次数：167 · 研究领域：Estrogen and related hormone effects、Growth Hormone and Insulin-like Growth Factors、Adipose Tissue and Metabolism

Rev-erbalpha [NR1D1], a member of the nuclear receptor superfamily, is an orphan receptor that constitutively represses gene transcription. Rev-erbalpha has been shown to play a role in myocyte differentiation and to be induced during adipogenesis. Furthermore, Rev-erbalpha is a regulator of lipoprotein metabolism. It was recently shown that Rev-erbalpha messenger RNA (mRNA) levels oscillate diurnally in rat liver. Here, we report that the circadian rhythm of Rev-erbalpha 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-erbalpha expression is also regulated by glucocorticoids. Treatment of rats with dexamethasone resulted in a decrease of Rev-erbalpha mRNA levels by 70% after 6 h. Furthermore, dexamethasone decreased Rev-erbalpha expression in rat primary hepatocytes in a dose-dependent fashion. This effect was mediated by the glucocorticoid receptor because simultaneous addition of the glucocorticoid antagonist RU486 prevented the decrease in Rev-erbalpha mRNA levels by dexamethasone. Protein synthesis inhibition with cycloheximide markedly induced Rev-erbalpha mRNA levels; however, this induction was reduced by dexamethasone supplementation in both rat and human primary hepatocytes. Treatment with actinomycin D blocked the repression of Rev-erbalpha expression by dexamethasone in rat hepatocytes, suggesting ...