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KMID : 0545120120220030378
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Journal of Microbiology and Biotechnology
2012 Volume.22 No. 3 p.378 ~ p.384
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Organotin Compounds Act as Inhibitor of Transcriptional Activation with Human Estrogen Receptor
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Cho Eun-Min
Lee Haeng-Seog
Moon Jeong-Suk
Kim Im-Soon
Sim Sang-Hyo
Akinori Ohta
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Abstract
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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 PPARγ. 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 β-galactosidase activity using the yeast two-hybrid detection system consisting of a combination of the human estrogen receptor (hERβ) 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 E2-dependent transcriptional activity, similar to antagonistic chemicals such as 4-hydroxytamoxifen (OHT) or ICI 182,780, at a very low concentration of 10-14M 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 hERβ LBD and the co-activator SRC1 in the yeast two-hybrid system. Consequently, our data could partly explain the occurrence of organotin compoundinduced imposex on the endocrine system of mammals, including humans.
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KEYWORD
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endocrine disruptors, imposex, TBT, TPT, hER, yeast two-hybrid system
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