Understanding the molecular basis for differences in responses of fish estrogen receptor subtypes to environmental estrogens

Environmental Science & Technology
Saki TohyamaTaisen Iguchi

Abstract

Exposure to endocrine disrupting chemicals (EDCs) can elicit adverse effects on development, sexual differentiation, and reproduction in fish. Teleost species exhibit at least three subtypes of estrogen receptor (ESR), ESR1, ESR2a, and ESR2b; thus, estrogenic signaling pathways are complex. We applied in vitro reporter gene assays for ESRs in five fish species to investigate the ESR subtype-specificity for better understanding the signaling pathway of estrogenic EDCs. Responses to bisphenol A, 4-nonylphenol, and o,p'-DDT varied among ESR subtypes, and the response pattern of ESRs was basically common among the different fish species. Using a computational in silico docking model and through assays quantifying transactivation of the LBD (using GAL-LBD fusion proteins and chimera proteins for the ESR2s), we found that the LBD of the different ESR subtypes generally plays a key role in conferring responsiveness of the ESR subtypes to EDCs. These results also indicate that responses of ESR2s to EDCs cannot necessarily be predicted from the LBD sequence alone, and an additional region is required for full transactivation of these receptors. Our data thus provide advancing understanding on receptor functioning for both basic and appl...Continue Reading

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Citations

Dec 29, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Saki TohyamaTaisen Iguchi
Apr 14, 2016·General and Comparative Endocrinology·Ryohei YatsuTaisen Iguchi
Apr 28, 2016·Epigenetics : Official Journal of the DNA Methylation Society·L V LaingE M Santos
Aug 22, 2016·Journal of Hazardous Materials·Jiangkun DuDionysios D Dionysiou
Jul 9, 2016·Environmental Science & Technology·Crystal S D Lee PowSeth W Kullman
Jan 10, 2021·The Science of the Total Environment·Hiroshi IshibashiKoji Arizono
Nov 16, 2020·Differentiation; Research in Biological Diversity·Taisen IguchiNoboru Takasugi
Mar 16, 2021·Frontiers in Endocrinology·Fritzie T Celino-BradyAndre P Seale

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