Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Organotin Compounds Act as Inhibitor of Transcriptional Activation with Human Estrogen Receptor

  • Cho, Eun-Min (Institute of Green Environmental Research Center, University of Incheon) ;
  • Lee, Haeng-Seog (New and Renewable Energy Company, North of Gyeonggi Venture Center) ;
  • Moon, Jeong-Suk (Green Technology Development Office, Korea Environmental Industry and Technology Institute) ;
  • Kim, Im-Soon (Graduate School of Environmental Studies, Kwangwoon University) ;
  • Sim, Sang-Hyo (Department of Occupational Medicine, Hanyang University Medical Center) ;
  • Ohta, Akinori (Department of Biotechnology, The University of Tokyo)
  • Received : 2011.05.18
  • Accepted : 2011.11.12
  • Published : 2012.03.28
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Abstract

In aquatic invertebrates, particularly marine gastropods, organotin compounds induce irreversible sexual abnormality in females, which is termed imposex, at very low concentrations. Organotin compounds are agonists for nuclear receptors such as RXRs and $PPAR{\gamma}$. However, the imposex phenomenon has not been reported to act as an antagonist on estrogen receptors in other species, including vertebrates and invertebrates. In order to gain insights into the antagonistic activity of organotin compounds on estrogen receptors (ERs), we examined the inhibitive effect of these compounds on estradiol-dependent ${\beta}$-galactosidase activity using the yeast two-hybrid detection system consisting of a combination of the human estrogen receptor ($hER{\beta}$) ligand-binding domain and the co-activator steroid receptor co-activator-1 (SRC1). Tributyltin-hydroxide (TBT-OH) and triphenyltin-chlorine (TPT-Cl) exhibited an inhibitive effect on $E_2$-dependent transcriptional activity, similar to antagonistic chemicals such as 4-hydroxytamoxifen (OHT) or ICI 182,780, at a very low concentration of $10^{-14}$ M TBT or $10^{-10}$ M TPT, respectively. The yeast growth and transcriptional activity with transcriptional factor GAL4 did not exhibit any effect at the tested concentration of TBT or TPT. Moreover, the yeast two-hybrid system using the interaction between p53 and the T antigen of SV40 large did not describe any effect at the tested concentration of OHT or ICI 182,780. However, the interaction between p53 and T antigen was inhibited at a TBT or TPT concentration of $10^{-9}$ M, respectively. These results indicate that TBT and TPT act as inhibitors of ER-dependent reporter gene transcriptional activation and of the interaction between $hER{\beta}$ LBD and the co-activator SRC1 in the yeast two-hybrid system. Consequently, our data could partly explain the occurrence of organotin compound-induced imposex on the endocrine system of mammals, including humans.

Keywords

References

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