title: Glucocorticoid receptor function in hepatocytes is essential to promote postnatal body growth.
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.
authors.affiliation: Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany.
authors.forename: François
authors.initials: F
authors.lastname: Tronche
authors.forename: Christian
authors.initials: C
authors.lastname: Opherk
authors.forename: Richard
authors.initials: R
authors.lastname: Moriggl
authors.forename: Christoph
authors.initials: C
authors.lastname: Kellendonk
authors.forename: Andreas
authors.initials: A
authors.lastname: Reimann
authors.forename: Lukas
authors.initials: L
authors.lastname: Schwake
authors.forename: Holger M
authors.initials: HM
authors.lastname: Reichardt
authors.forename: Katharina
authors.initials: K
authors.lastname: Stangl
authors.forename: Daniel
authors.initials: D
authors.lastname: Gau
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeflich
authors.forename: Hartmut
authors.initials: H
authors.lastname: Beug
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schmid
authors.forename: Günther
authors.initials: G
authors.lastname: Schütz
mesh_terms: D000818:Animals; D001824:Body Constitution; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006128:Growth; D013006:Growth Hormone / Q000097:blood / Q000502:physiology; D022781:Hepatocytes / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008894:Milk Proteins; D009928:Organ Specificity; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D008894:Milk Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D013006:Growth Hormone