Glucocorticoid receptor function in hepatocytes is essential to promote postnatal body growth.
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.
Tronche
François
F
Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany.
Opherk
Christian
C
Moriggl
Richard
R
Kellendonk
Christoph
C
Reimann
Andreas
A
Schwake
Lukas
L
Reichardt
Holger M
HM
Stangl
Katharina
K
Gau
Daniel
D
Hoeflich
Andreas
A
Beug
Hartmut
H
Schmid
Wolfgang
W
Schütz
Günther
G
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
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D013006:Growth Hormone