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Time-Dependent transcriptional profiles of genes of the hypothalamic-pituitary-gonadal axis in medaka (Oryzias latipes) exposed to fadrozole and 17β-trenbolone

Authors

  • Xiaowei Zhang,

    Corresponding author
    1. Department of Zoology, Michigan State University, East Lansing, Michigan 48824, USA
    2. National Food Safety and Toxicology Center and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, USA
    • Department of Zoology, Michigan State University, East Lansing, Michigan 48824, USA
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  • Markus Hecker,

    1. National Food Safety and Toxicology Center and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, USA
    2. ENTRIX, Saskatoon, Saskatchewan S7N 5B3, Canada
    3. Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B3, Canada
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  • June-Woo Park,

    1. Department of Zoology, Michigan State University, East Lansing, Michigan 48824, USA
    2. National Food Safety and Toxicology Center and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, USA
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  • Amber R. Tompsett,

    1. Department of Zoology, Michigan State University, East Lansing, Michigan 48824, USA
    2. National Food Safety and Toxicology Center and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, USA
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  • Paul D. Jones,

    1. National Food Safety and Toxicology Center and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, USA
    2. Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B3, Canada
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  • John Newsted,

    1. National Food Safety and Toxicology Center and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, USA
    2. ENTRIX, Okemos, Michigan 48864, USA
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  • Doris W. T. Au,

    1. Department of Biology and Chemistry, City University of Hong Kong, Hong Kong, Special Administration Region, China
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  • Richard Kong,

    1. Department of Biology and Chemistry, City University of Hong Kong, Hong Kong, Special Administration Region, China
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  • Rudolf S. S. Wu,

    1. Department of Biology and Chemistry, City University of Hong Kong, Hong Kong, Special Administration Region, China
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  • John P. Giesy

    1. Department of Zoology, Michigan State University, East Lansing, Michigan 48824, USA
    2. National Food Safety and Toxicology Center and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, USA
    3. Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B3, Canada
    4. Department of Biomedical Veterinary Sciences, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B3, Canada
    5. Department of Biology and Chemistry, City University of Hong Kong, Hong Kong, Special Administration Region, China
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Abstract

Both the anabolic androgen 17β-trenbolone (TRB) and the aromatase inhibitor fadrozole (FAD) can cause decreased plasma concentrations of estrogen (E2) and reduce fecundity of fish. However, the underlying mechanisms and the molecular pathways involved are largely unknown. The present study was designed to assess time-dependent effects of FAD and TRB on the transcriptional responses of the hypothalamic-pituitary-gonadal (HPG) axis of Japanese medaka (Oryzias latipes). Fourteen-week-old Japanese medaka were exposed to 50 μg FAD/L or 2 μg TRB/L in a 7-d static renewal test, and the expression profiles of 36 HPG axis genes were measured by means of a medaka HPG real-time reverse-transcription polymerase chain reaction array after 8 h, 32 h, or 7 d of exposure. Exposure to TRB or FAD caused lesser fecundity of Japanese medaka and down-regulated transcription of vitellogenin and choriogenin (CHG) gene expression in the liver of females. Exposure to FAD for 8 h resulted in an 8-fold and 71-fold down-regulation of expression of estrogen receptor α and choriogenin L (CHG L), respectively, in female liver. 17β-Trenbolone caused similar down-regulation of these genes, but the effects were not observed until 32 h of exposure. These results support the hypothesis that FAD reduces plasma E2 more quickly by inhibiting aromatase enzyme activity than does TRB, which inhibits the production of the E2 precursor testosterone. Exposure to FAD and TRB resulted in rapid (after 8 h) down-regulation of luteinizing hormone receptor and low-density-lipoprotein receptor in the testis to compensate for excessive androgen levels. Overall, the molecular responses observed in the present study differentiate the mechanisms of the reduced fecundity by TRB and FAD.

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