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Effects of Long-Term In Vivo Exposure to Di-2-Ethylhexylphthalate on Thyroid Hormones and the TSH/TSHR Signaling Pathways in Wistar Rats

Author

Listed:
  • Xinwen Dong

    (Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China)

  • Jin Dong

    (Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China)

  • Yue Zhao

    (Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China)

  • Jipeng Guo

    (Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China)

  • Zhanju Wang

    (Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China)

  • Mingqi Liu

    (Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China)

  • Yunbo Zhang

    (Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China)

  • Xiaolin Na

    (Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin 150081, China)

Abstract

Di-(2-ethylhexyl)phthalate (DEHP) was a widely used chemical with human toxicity. Recent in vivo and in vitro studies suggested that DEHP-exposure may be associated with altered serum thyroid hormones (THs) levels, but the underlying molecular mechanisms were largely unknown. To explore the possible molecular mechanisms, 128 Wistar rats were dosed with DEHP by gavage at 0, 150, 300, and 600 mg/kg/day for 3 months (M) and 6 M, respectively. After exposure, expression of genes and proteins in the thyroid, pituitary, and hypothalamus tissues of rats were analyzed by Q-PCR and western blot, while the sera and urine samples were assayed by radioimmunoassay and ELISA. Results showed that serum THs levels were suppressed by DEHP on the whole. DEHP treatment influenced the levels of rats’ thyrotropin releasing hormone receptor (TRHr), Deiodinases 1 (D1), thyroid stimulating hormone beta (TSHβ), sodium iodide symporter (NIS), thyroid stimulating hormone receptor (TSHr), thyroperoxidase (TPO), thyroid transcription factor 1 (TTF-1), and thyroglobulin (TG) mRNA/protein expression in the hypothalamus-pituitary-thyroid (HPT) axis and decreased urine iodine. Taken together, observed findings indicate that DEHP could reduce thyroid hormones via disturbing the HPT axis, and the activated TSH/TSHR pathway is required to regulate thyroid function via altering TRHr, TSHβ, NIS, TSHr, TPO, TTF-1 and TG mRNA/protein expression of the HPT axis.

Suggested Citation

  • Xinwen Dong & Jin Dong & Yue Zhao & Jipeng Guo & Zhanju Wang & Mingqi Liu & Yunbo Zhang & Xiaolin Na, 2017. "Effects of Long-Term In Vivo Exposure to Di-2-Ethylhexylphthalate on Thyroid Hormones and the TSH/TSHR Signaling Pathways in Wistar Rats," IJERPH, MDPI, vol. 14(1), pages 1-14, January.
    • Handle: RePEc:gam:jijerp:v:14:y:2017:i:1:p:44-:d:86897
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    Citations

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    Cited by:

    1. Angela Giuliani & Mariachiara Zuccarini & Angelo Cichelli & Haroon Khan & Marcella Reale, 2020. "Critical Review on the Presence of Phthalates in Food and Evidence of Their Biological Impact," IJERPH, MDPI, vol. 17(16), pages 1-43, August.
    2. Yuanyuan Huang & Chuancheng Wu & Youbin Ye & Jingwen Zeng & Jianlin Zhu & Yuchen Li & Wenxiang Wang & Wenchang Zhang & Yiqin Chen & Hongyuan Xie & Hongmei Zhang & Jin Liu, 2019. "The Increase of ROS Caused by the Interference of DEHP with JNK/p38/p53 Pathway as the Reason for Hepatotoxicity," IJERPH, MDPI, vol. 16(3), pages 1-14, January.

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