Understanding the Molecular Basis for Differences in Responses of Fish Estrogen Receptor Subtypes to Environmental Estrogens

Saki Tohyama, Shinichi Miyagawa, Anke Lange, Yukiko Ogino, Takeshi Mizutani, Norihisa Tatarazako, Yoshinao Katsu, Masaru Ihara, Hiroaki Tanaka, Hiroshi Ishibashi, Tohru Kobayashi, Charles R. Tyler, Taisen Iguchi

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33 Citations (Scopus)

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 applied research.

Original languageEnglish
Pages (from-to)7439-7447
Number of pages9
JournalEnvironmental Science and Technology
Volume49
Issue number12
DOIs
Publication statusPublished - 16 Jun 2015

Cite this

Tohyama, S., Miyagawa, S., Lange, A., Ogino, Y., Mizutani, T., Tatarazako, N., Katsu, Y., Ihara, M., Tanaka, H., Ishibashi, H., Kobayashi, T., Tyler, C. R., & Iguchi, T. (2015). Understanding the Molecular Basis for Differences in Responses of Fish Estrogen Receptor Subtypes to Environmental Estrogens. Environmental Science and Technology, 49(12), 7439-7447. https://doi.org/10.1021/acs.est.5b00704