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Volume 272, Number 39, Issue of September 26, 1997 pp. 24514-24521
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential Regulation by Tumor Necrosis Factor-alpha of beta 1-, beta 2-, and beta 3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

(Received for publication, April 7, 1997, and in revised form, June 27, 1997)

Khadija El Hadri , Annie Courtalon , Xavier Gauthereau , Anne-Marie Chambaut-Guérin , Jacques Pairault and Bruno Fève

From INSERM Unité 282, Hôpital Henri Mondor, 94010 Créteil, France

Modulation of beta -adrenoreceptor expression by tumor necrosis factor-alpha (TNF-alpha ) was investigated in murine 3T3-F442A adipocytes. TNF-alpha treatment of mature adipocytes decreased beta 3-adrenoreceptor mRNA content in a time- and concentration-dependent manner, with a 8.5-fold decrease observed after a 6-h exposure to 300 pM TNF-alpha . beta 1-Adrenoreceptor mRNA abundance was slightly decreased by TNF-alpha treatment, while beta 2-adrenoreceptor mRNA levels were potently induced (6-fold increase at 6 h). (-)-[125I]Iodocyanopindolol saturation and competition binding experiments indicated that TNF-alpha induced a 2-fold decrease in beta 3-adrenoreceptor number, a nonsignificant reduction in beta 1-subtype population, and a ~4.5-fold increase in beta 2-adrenoreceptor density. This correlated with a lower EC50 value measured for epinephrine in stimulating adenylyl cyclase, whereas the EC50 value for norepinephrine increased. Nuclear run-on assays on isolated nuclei and mRNA stability measurements showed that TNF-alpha increased both beta 2-adrenoreceptor gene transcription and beta 2-adrenoreceptor mRNA half-life, while beta 1- and beta 3-adrenoreceptor gene expression was modulated only at the transcriptional level by the cytokine. These findings demonstrate a differential modulation by TNF-alpha of the three beta -adrenoreceptor subtypes in adipocytes, which may contribute to metabolic disorders induced by the cytokine in the adipocyte.


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