Regulation of mouse beta 3-adrenergic receptor gene expression and mRNA splice variants in adipocytes.
This study examined the regulation of murine beta 3-receptor mRNA and determined whether the recently described mRNA splice variants are differentially regulated by agents that alter total beta 3-receptor mRNA levels. In vivo treatment of mice with the beta 3-receptor agonist BRL-26830 reduced total beta 3-transcripts by 64% in white adipose tissue but did not alter the mRNA splicing pattern. Further analysis in cultured 3T3-F442A adipocytes showed that isoproterenol, dexamethasone, or phorbol 12-myristate 13-acetate also greatly reduced beta 3-receptor mRNA levels without selectively altering poly-U-containing transcripts. Blockade of transcription with actinomycin D produced a rapid loss of beta 3-receptor mRNA, which was prevented by blockade of mRNA translation with cycloheximide. However, neither actinomycin D nor cycloheximide altered the splicing pattern of beta 3-receptor mRNA. Analysis of transcription rate by nuclear run-off assay indicated that 8-bromoadenosine 3',5'-cyclic monophosphate and phorbol 12-myristate 13-acetate reduce beta 3-receptor gene transcription and that suppression of transcription is sufficient to account for the reduction in beta 3-receptor mRNA levels by these agents.
Granneman
J G
JG
Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Lahners
K N
KN
D016475:3T3 Cells; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D005786:Gene Expression Regulation; D014644:Genetic Variation; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D011494:Protein Kinases / Q000502:physiology; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D015290:Second Messenger Systems; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D003907:Dexamethasone; D003513:Cycloheximide; D011494:Protein Kinases; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate