Aryl hydrocarbon receptor-mediated suppression of GH receptor and Janus kinase 2 expression in mice

FEBS Lett. 2004 Jan 30;558(1-3):96-100. doi: 10.1016/S0014-5793(03)01528-X.

Abstract

Differential mRNA display revealed that a cDNA encoding the major urinary protein 2 (MUP2) that belongs to the lipocalin superfamily was absent in livers of mice treated with 3-methylcholanthrene (MC). The expression of MUP2 is known to be stimulated by growth hormone (GH), through the GH receptor (GHR), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) signal transduction pathway. Since MC is an aryl hydrocarbon receptor (AhR) ligand, the effects of MC treatment on the expression of GHR, JAK2 or STAT5 in the livers of wild-type or AhR-null mice were examined. The result indicated that the expression of GHR and JAK2 mRNA was greatly decreased by MC in wild-type mice but not in AhR-null mice. In addition, the binding activity of STAT5 bound to STAT5-binding element was reduced after MC treatment in wild-type mice but not in AhR-null mice. Based on these results, we conclude that the suppression of MUP2 mRNA expression by MC is caused by the AhR-mediated disruption of the GH signaling pathway. Possible mechanism(s) by which exposure to aromatic hydrocarbons causes a decrease in the body weight of mice, which has been referred to as wasting syndrome, will also be discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Carcinogens / toxicity*
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Enzymologic
  • Gene Silencing
  • Janus Kinase 2
  • Male
  • Methylcholanthrene / toxicity*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Milk Proteins*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Receptors, Somatotropin / drug effects
  • Receptors, Somatotropin / metabolism*
  • STAT5 Transcription Factor
  • Signal Transduction / drug effects
  • Trans-Activators / drug effects
  • Trans-Activators / metabolism
  • Wasting Syndrome / etiology

Substances

  • Carcinogens
  • DNA-Binding Proteins
  • Milk Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Receptors, Somatotropin
  • STAT5 Transcription Factor
  • Stat5a protein, mouse
  • Trans-Activators
  • Methylcholanthrene
  • Protein-Tyrosine Kinases
  • Jak2 protein, mouse
  • Janus Kinase 2