Tronche François, 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
Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany.
Genes Dev. 2004 Mar 1;18(5):492-7. doi: 10.1101/gad.284704.
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.
携带糖皮质激素受体（GR）基因肝细胞特异性失活的小鼠体型显著减小。由Stat5转录因子介导的生长激素信号传导受损。我们发现Stat5蛋白与GR发生物理相互作用，并且GR在体内存在于Stat5依赖性IGF-I和ALS调控区域。有趣的是，具有DNA结合缺陷型GR但与STAT5相互作用能力未改变的小鼠（GR(dim/dim)）具有正常体型和正常水平的Stat5依赖性mRNA。这些发现有力地支持了GR在生长激素刺激下作为Stat5依赖性转录的共激活因子发挥作用的模型，并揭示了肝脏GR在控制身体生长中的重要作用。
