Stimulation of hepatic signal transducer and activator of transcription 5b by GH is not altered by 3-methylcholanthrene

Endocrinology. 2002 Sep;143(9):3284-94. doi: 10.1210/en.2002-220212.


We are investigating the mechanisms by which aromatic hydrocarbons, such as 3-methylcholanthrene (MC), suppress hepatic cytochrome P450 2C11 (CYP2C11) gene expression. CYP2C11 is an enzyme expressed in the liver of male rats and is regulated by a pulsatile pattern of GH secretion. We have previously shown that MC attenuates the stimulatory effect of GH on CYP2C11 expression in hypophysectomized male rats. In follow-up studies we evaluated the effect of MC on GH-stimulated signal transducer and activator of transcription 5b (STAT5b) phosphorylation, nuclear translocation, and DNA-binding activity. GH-stimulated increases in hepatic nuclear STAT5b and phospho-STAT5b levels were not different between groups of hypophysectomized rats receiving MC or vehicle. This observation was corroborated at the DNA-binding level by EMSA. We also measured GH-induced STAT5b activation in the H4IIE rat hepatoma cell line. STAT5b DNA-binding activity detected in GH-treated cells was not affected by MC. Immunocytochemistry experiments revealed no effect of MC on GH-stimulated STAT5b nuclear translocation in H4IIE cells. These in vivo and in vitro data suggest that interference with GH-stimulated STAT5b activation does not constitute a mechanism by which MC attenuates the stimulatory effect of GH on CYP2C11 gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Biological Transport
  • Caseins / genetics
  • Cell Nucleus / metabolism
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Growth Hormone / pharmacology*
  • Hypophysectomy
  • Immunoblotting
  • Immunohistochemistry
  • Immunosorbent Techniques
  • Liver / chemistry*
  • Liver Neoplasms, Experimental
  • Male
  • Methylcholanthrene / pharmacology*
  • Milk Proteins*
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Rats
  • Rats, Inbred F344
  • STAT5 Transcription Factor
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transfection
  • Tumor Cells, Cultured


  • Caseins
  • DNA-Binding Proteins
  • Milk Proteins
  • STAT5 Transcription Factor
  • Stat5b protein, rat
  • Trans-Activators
  • Phosphotyrosine
  • Methylcholanthrene
  • Growth Hormone
  • DNA