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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- of
1-, 2-, and
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 -adrenoreceptor expression by
tumor necrosis factor- (TNF- ) was investigated in murine
3T3-F442A adipocytes. TNF- treatment of mature adipocytes decreased
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- . 1-Adrenoreceptor mRNA abundance was slightly
decreased by TNF- treatment, while 2-adrenoreceptor
mRNA levels were potently induced (6-fold increase at 6 h).
( )-[125I]Iodocyanopindolol saturation and competition
binding experiments indicated that TNF- induced a 2-fold decrease in
3-adrenoreceptor number, a nonsignificant reduction in
1-subtype population, and a ~4.5-fold increase in
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- increased both
2-adrenoreceptor gene transcription and
2-adrenoreceptor mRNA half-life, while
1- and 3-adrenoreceptor gene expression
was modulated only at the transcriptional level by the cytokine. These
findings demonstrate a differential modulation by TNF- of the three
-adrenoreceptor subtypes in adipocytes, which may contribute to
metabolic disorders induced by the cytokine in the adipocyte.

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Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.
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