Transcriptional and posttranscriptional mechanisms of glucocorticoid- mediated repression of phosphoenolpyruvate carboxykinase gene expression in adipocytes

Sylvie Franckhauser-Vogel, Jocelyne Antras-Ferry, Danielle Robin, Pierre Robin, Claude Forest*

*Autor corresponent d’aquest treball

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Resum

Glucocorticoids exert pleiotropic effects, among which negative regulation of transcription has been recognized as of crucial importance. While glucocorticoids induce phosphoenolpyruvate carboxykinase (PEPCK) gene expression in liver cells, it represses gene activity in adipose cells. We used the 3T3-F442A adipocytes to analyze the underlying mechanisms. In these cells, the synthetic glucocorticoid dexamethasone exerts a dominant repression either on basal or on β-agonist stimulation of PEPCK gene expression. To determine whether glucocorticoid action required protein synthesis, we employed cycloheximide, anisomycin, and puromycin, three different translation inhibitors. None of these affected induction by isoprenaline or repression by dexamethasone of isoprenaline stimulation. In contrast, dexamethasone inhibitory action on basal PEPCK mRNA was totally prevented by the three translation inhibitors. Time courses of glucocorticoid action on basal and on induction by β-agonist were similar. Half-maximal effect of dexamethasone on isoprenaline-induced PEPCK mRNA was obtained at about 10 nM, a tenfold higher concentration than that observed for the reduction of basal mRNA. Using the transcription inhibitor DRB, we showed that dexamethasone did not alter mRNA half-life, while isoprenaline strongly stabilized mRNA. In a 3T3-F442A stable transfectant bearing -2,100 base pairs of the PEPCK promoter fused to the chloramphenicol acetyltransferase (CAT) gene, isoprenaline stimulated CAT activity, whereas dexamethasone reduced basal and isoprenaline-induced CAT expression. Hence, β-agonists exert both transcriptional and posttranscriptional regulation, while glucocorticoid action is purely transcriptional. However, mechanisms of glucocorticoid repression of basal and of β-agonist stimulation appear different.
Idioma originalAnglès
Pàgines (de-a)386-393
Nombre de pàgines8
RevistaJournal of Cellular Biochemistry
Volum66
Número3
DOIs
Estat de la publicacióPublicada - 1 de set. 1997

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