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Transactivational property of chemicals via medaka glucocorticoid receptor 1b using a stable reporter gene assay

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Abstract

The transactivational property of natural and synthetic chemicals via medaka GR1b was investigated after development of a stable cell line for the reporter gene assay. In our study, cortisol was the most potent agonist among the natural corticoids assayed for potency [EC50 (concentration of agonist provoking a response halfway between the baseline and maximum response) 68 nM] and efficacy. Three artificial corticosteroids, namely, dexamethasone [EC50 16 nM, relative agonistic activity to cortisol (RAA) 144 %], prednisolone (EC50 81 nM, RAA 116 %) and clobetasol propionate (EC50 0.10 nM, RAA 220 %), showed strong agonistic activity and were more potent than the original corticoid, F. All synthetic corticoids used in our study were full agonists. Interestingly, melengestrol acetate, a synthetic progestogen, induced luciferase activity in a dose-dependent manner. Based on its EC50 value and RAA of 29 nM and 57 %, respectively, this molecule was assessed as a partial agonist. None of the other steroids and chemicals assayed in our study induced an agonistic response. In conclusion, we successfully developed a stable reporter gene assay that can be used to assess the transactivational property of glucocorticoid-like chemicals toward medaka GR1b.

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Authors and Affiliations

  1. Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, 526-0829, Japan

    Kazuya Sato, Masaki Okamoto, Yuta Suzuki, Kagehisa Kiba, Hiroki Tatsumi, Hisashi Teramura & Toshitaka Ikeuchi

  2. Laboratory of Molecular Response to Environmental Signal, Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Tamuracho 1266, Nagahama, Shiga, 526-0829, Japan

    Toshitaka Ikeuchi

Authors
  1. Kazuya Sato
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  2. Masaki Okamoto
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  3. Yuta Suzuki
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  4. Kagehisa Kiba
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  5. Hiroki Tatsumi
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  6. Hisashi Teramura
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  7. Toshitaka Ikeuchi
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Correspondence to Toshitaka Ikeuchi.

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Sato, K., Okamoto, M., Suzuki, Y. et al. Transactivational property of chemicals via medaka glucocorticoid receptor 1b using a stable reporter gene assay. Fish Sci 79, 943–948 (2013). https://doi.org/10.1007/s12562-013-0679-5

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  • DOI: https://doi.org/10.1007/s12562-013-0679-5

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