Low dose exposure to Di-2-ethylhexylphthalate in Juvenile rats alters the expression of genes related with thyroid hormone regulation

Minjeong Kim, Ji Seong Jeong, Hyunji Kim, Seungwoo Hwang, Il Hyun Park, Byung Chul Lee, Sung Il Yoon, Sun Ha Jee, Ki Taek Nam, Kyung Min Lim

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20 Citations (Scopus)


Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.

Original languageEnglish
Pages (from-to)512-519
Number of pages8
JournalBiomolecules and Therapeutics
Issue number5
Publication statusPublished - 2018 Sept

Bibliographical note

Funding Information:
This research was supported by grants from Ministry of Food and Drug Safety in 2015 (15162MFDS631), Basic Science Research Program through National Research Foundation of Korea (NRF) funded by the Ministry of Education (2014R1A1A2058657 and NRF-2017R1A2B2009850) and the Korea government(MSIT) (No. 2018R1A5A2025286). We appreciate the assistance from the KOBIC Research Support Program.

Publisher Copyright:
© 2018 The Korean Society of Applied Pharmacology.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery


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