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Aryl hydrocarbon receptor‐mediated suppression of GH receptor and Janus kinase 2 expression in mice
Author(s) -
Nukaya Manabu,
Takahashi Yoshiki,
Gonzalez Frank J,
Kamataki Tetsuya
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01528-x
Subject(s) - stat5 , aryl hydrocarbon receptor , janus kinase 2 , growth hormone receptor , stat protein , signal transduction , janus kinase , medicine , receptor , endocrinology , aryl hydrocarbon receptor nuclear translocator , stat3 , biology , messenger rna , chemistry , microbiology and biotechnology , transcription factor , hormone , biochemistry , growth hormone , gene
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.