Glucocorticoid receptor function in hepatocytes is essential to promote postnatal body growth
- François Tronche1,2,6,
- Christian Opherk1,6,
- Richard Moriggl3,6,
- Christoph Kellendonk1,
- Andreas Reimann4,
- Lukas Schwake1,
- Holger M. Reichardt1,
- Katharina Stangl3,
- Daniel Gau1,
- Andreas Hoeflich5,
- Hartmut Beug3,
- Wolfgang Schmid1, and
- Günther Schütz1,7
- 1Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany; 2Molecular Genetics and Neurophysiology, Collège de France, 75231 Paris Cedex 05, France; 3Institute of Molecular Pathology, A-1030 Vienna, Austria; 4Unité Expression génétique et Maladies, Département de Biologie du Développement, Institut Pasteur, 75724 Paris cedex 15, France; 5Lehrstuhl für Molekulare Tierzucht und Haustiergenetik, Genzentrum, 81377 Muenchen, Germany
Abstract
Mice carrying a hepatocyte-specific inactivation of the glucorticoid receptor (GR) gene show a dramatic reduction in body size. Growth hormone signaling mediated by the Stat5 transcription factors is impaired. We show that Stat5 proteins physically interact with GR and GR is present in vivo on Stat5-dependent IGF-I and ALS regulatory regions. Interestingly, mice with a DNA-binding-deficient GR but an unaltered ability to interact with STAT5 (GRdim/dim) have a normal body size and normal levels of Stat5-dependent mRNAs. These findings strongly support the model in which GR acts as a coactivator for Stat5-dependent transcription upon GH stimulation and reveal an essential role of hepatic GR in the control of body growth.
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Footnotes
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.284704.
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↵6 These authors contributed equally to this work.
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↵7 Corresponding author.
↵7 E-MAIL g.schuetz{at}dkfz.de; FAX 49-6221-42-3470.
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- Accepted January 27, 2004.
- Received September 8, 2003.
- Cold Spring Harbor Laboratory Press
