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DEHP reduces thyroid hormones via interacting with hormone synthesis-related proteins, deiodinases, transthyretin, receptors, and hepatic enzymes in rats

Environmental Science and Pollution Research volume 22, pages 12711–12719 (2015)Cite this article

Abstract

Di-(2-ethylhexyl) phthalate (DEHP) is used extensively in many personal care and consumer products, resulting in widespread nonoccupational human exposure through multiple routes and media. Limited studies suggest that exposure to DEHP may be associated with altered thyroid function, but detailed mechanisms are unclear. In order to elucidate potential mechanisms by which DEHP disturbs thyroid hormone homeostasis, Sprague-Dawley (SD) rats were dosed with DEHP by gavage at 0, 250, 500, and 750 mg/kg/day for 30 days and sacrificed within 24 h after the last dose. Gene expressions of thyroid hormone receptors, deiodinases, transthyretin, and hepatic enzymes were measured by RT-PCR; protein levels of transthyretin were also analyzed by Western blot. Results showed that DEHP caused histological changes in the thyroid and follicular epithelial cell hypertrophy and hyperplasia were observed. DEHP significantly reduced thyroid hormones (T3, T4) and thyrotropin releasing hormone (TRH) levels, whereas thyroid stimulating hormone (TSH) was not affected. After exposure to DEHP, biosynthesis of thyroid hormones was suppressed, and sodium iodide symporter (NIS) and thyroid peroxidase (TPO) levels were significantly reduced. Additionally, levels of deiodinases and transthyretin were also affected. TSH receptor (TSHr) level was downregulated, while TRH receptor (TRHr) level was upregulated. Metabolism of thyroid hormones was accelerated due to elevated gene expression of hepatic enzymes (UDPGTs and CYP2B1) by DEHP. Taken together, observed findings indicate that DEHP could reduce thyroid hormones through influencing biosynthesis, biotransformation, biotransport, receptor levels, and metabolism of thyroid hormones.

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Acknowledgments

This work was supported by grants from the Chongqing Population and Family Planning Science and Technology Research Institute (CSTC-JBKY-1701401).

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Authors and Affiliations

  1. Key Lab of Birth Defects and Reproductive Health of National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, 18 Honghuang Road, Chongqing, 400020, People’s Republic of China

    Changjiang Liu, Letian Zhao, Li Wei & Lianbing Li

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  1. Changjiang Liu
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  2. Letian Zhao
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  3. Li Wei
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  4. Lianbing Li
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Correspondence to Lianbing Li.

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Responsible editor: Markus Hecker

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Liu, C., Zhao, L., Wei, L. et al. DEHP reduces thyroid hormones via interacting with hormone synthesis-related proteins, deiodinases, transthyretin, receptors, and hepatic enzymes in rats. Environ Sci Pollut Res 22, 12711–12719 (2015). https://doi.org/10.1007/s11356-015-4567-7

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  • DOI: https://doi.org/10.1007/s11356-015-4567-7

Keywords

  • DEHP
  • Thyroid hormone
  • Receptor
  • Hepatic enzyme
  • Deiodinase
  • Transthyretin
  • Biosynthesis