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

FEBS Letters

Gonzalez, Frank J¹  Kamataki, Tetsuya²  Takahashi, Yoshiki²  Nukaya, Manabu² 

[1] Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892, USA;Laboratory of Drug Metabolism, Division of Pharmacobio-dynamics, Graduate School of Pharmaceutical Sciences, Hokkaido University, N12W6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

关键词: Aryl hydrocarbon receptor;    Growth hormone receptor;    3-Methylcholanthrene;    Janus kinase 2;    Major urinary protein;    Signal transducer and activator of transcription 5;    Wasting syndrome;    AhR;    aryl hydrocarbon receptor;    Arnt;    AhR nuclear translocator;    CIS;    cytokine-inducible SH2-containing protein;    CYP;    cytochrome P450;    EMSA;    electrophoretic mobility shift assay;    GAS;    γ-interferon-activated site;    GH;    growth hormone;    GHR;    growth hormone receptor;    JAK2;    Janus kinase 2;    MC;    3-methylcholanthrene;    MUP;    major urinary protein;    PAH;    polycyclic aromatic hydrocarbon;    PCR;    polymerase chain reaction;    RT;    reverse transcription;    STAT;    signal transducer and activator of transcription;    TCDD;    2;    3;    7;    8-tetrachlorodibenzo-p-dioxin;    WAP;    α-whey acidic protein;    WT;    wild-type;    XRE;    xenobiotic-responsive element;   

DOI  :  10.1016/S0014-5793(03)01528-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown