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PMID: 15037546 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Glucocorticoid receptor function in hepatocytes is essential to promote postnatal body growth.

Genes & development ·Vol. 18 ·No. 5 ·2004-03-01 ·Pages 492-7

Tronche F, Opherk C, Moriggl R, Kellendonk C, Reimann A, Schwake L, Reichardt HM, Stangl K, Gau D, Hoeflich A, Beug H, Schmid W, Schütz G

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 (GR(dim/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.

MeSH Terms
Animals Body Constitution DNA-Binding Proteins/genetics,metabolism Female Growth Growth Hormone/blood,physiology Hepatocytes/metabolism,physiology Male Mice Mice, Mutant Strains Milk Proteins Organ Specificity Protein Binding RNA, Messenger/analysis Receptors, Glucocorticoid/genetics,metabolism,physiology STAT5 Transcription Factor Signal Transduction Trans-Activators/genetics,metabolism Transcription, Genetic
Chemicals
DNA-Binding Proteins Milk Proteins RNA, Messenger Receptors, Glucocorticoid STAT5 Transcription Factor Trans-Activators Growth Hormone
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Tronche François
Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany.
Opherk Christian
Moriggl Richard
Kellendonk Christoph
Reimann Andreas
Schwake Lukas
Reichardt Holger M
Stangl Katharina
Gau Daniel
Hoeflich Andreas
Beug Hartmut
Schmid Wolfgang
Schütz Günther
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.284704
Published
2004-03-01
Pages
492-7
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC374231
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.284704 PMC Full Text View journal details
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