Opposing effects of glucocorticoids on beta(3)-adrenergic receptor expression in HIB-1B brown adipocytes.
Glucocorticoids (GC) have been reported to promptly repress beta(3)-adrenergic receptor (beta(3)-AR) gene transcription in a white adipose tissue cell line. However, the effect of these hormones on beta(3)-AR expression in brown adipose tissue in vivo suggests a more complex mechanism of action. To avoid potential in vivo confounding variables, we investigated the effect of GC on the beta(3)-AR of HIB-1B brown adipocytes. While beta(3)-AR mRNA had same rapid turnover as in white fat cells, 1.5-2 h, the time course of its descent following dexamethasone was complex. A rapid initial descent beta(3)-AR mRNA with t(1/2) approximately 1.6 h was consistent with a prompt, complete inhibition of transcription. Such rapid initial phase was followed approximately 2 h later by a plateau or even an increase of beta(3)-AR mRNA, to descend thereafter following a slower single exponential (t(1/2) approximately 10 h). The change in the time course was abrogated by cycloheximide, and was not due to dexamethasone degradation or stabilization of beta(3)-AR mRNA at later times after dexamethasone. In vivo, a sufficiently large dose of dexamethasone was associated with a transient approximately 70% reduction of brown adipose tissue beta(3)-AR mRNA by 4 h and full recovery by 24 h. These findings suggest that GC have two opposing effects on beta(3)-AR gene expression: they rapidly and directly inhibit transcription but also induce a rapidly turned-over protein (C/EBPbeta?) that stimulates gene transcription. The relative magnitude of these two effects may vary explaining apparently discrepant observations.
Bakopanos
Evangelos
E
Division of Endocrinology and Metabolism, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Room E-162, 3755 Chemin de la Côte-Ste-Catherine, Montreal, Quebec, Canada H3T 1E2.
Silva
J Enrique
JE
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009687:Nuclear Proteins / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020871:RNA Stability; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D005938:Glucocorticoids; D009687:Nuclear Proteins; D011500:Protein Synthesis Inhibitors; D022702:Receptors, Adrenergic, beta-3; D014157:Transcription Factors; D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide