Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Endocrine Disrupting Organotin Compounds are Potent Inducers of Imposex in Gastropods and Adipogenesis in Vertebrates

  • Iguchi, Taisen (Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, and Department of Basic Biology, Faculty of Life Science, the Graduate University for Advanced Studies) ;
  • Katsu, Yoshinao (Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, and Department of Basic Biology, Faculty of Life Science, the Graduate University for Advanced Studies) ;
  • Horiguchi, Toshihiro (Core Research for Evolutional Science and Technology Science and Technology Corporation) ;
  • Watanabe, Hajime (Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, and Department of Basic Biology, Faculty of Life Science, the Graduate University for Advanced Studies) ;
  • Blumberg, Bruce (Department of Developmental and Cell Biology, University of California Irvine) ;
  • Ohta, Yasuhiko (Core Research for Evolutional Science and Technology Science and Technology Corporation)
  • Published : 2007.03.31
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Abstract

The persistent and ubiquitous environmental contaminant, tributyltin chloride (TBT), induces not only imposex in gastropods but also the differentiation of adipocytes in vitro and increases adipose mass in vivo in vertebrates. TBT is a nanomolar affinity ligand for retinoid X receptor (RXR) in the rock shell(Thais clavigera) and for both the RXR and the peroxisome proliferator activated receptor $\gamma(PPAR\gamma)$ in the amphibian (Xenopus laevis), mouse, and human. The molecular mechanisms underlying induction of imposex by TBT have not been clarified, though several hypotheses are proposed. TBT promotes adipogenesis in the murine 3T3-L1 cell model and perturbs key regulators of adipogenesis and lipogenic pathways in vivo primarily through activation of RXR and $PPAR\gamma$. Moreover, in utero exposure to TBT leads to strikingly elevated lipid accumulation in adipose depots, liver, and testis of neonate mice and results in increased adipose mass in adults. In X. laevis, ectopic adipocytes form in and around gonadal tissues following organotin, RXR or $PPAR\gamma$ ligand exposure. TBT represents the first example of an environmental endocrine disrupter that promotes adverse effects from gastropods to mammals.

Keywords

References

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