Skip Navigation
Skip to contents

Endocrinol Metab : Endocrinology and Metabolism


Author index

Page Path
Kyungho Choi 1 Article
Endocrine Research
DEHP Down-Regulates Tshr Gene Expression in Rat Thyroid Tissues and FRTL-5 Rat Thyrocytes: A Potential Mechanism of Thyroid Disruption
Min Joo Kim, Hwan Hee Kim, Young Shin Song, Ok-Hee Kim, Kyungho Choi, Sujin Kim, Byung-Chul Oh, Young Joo Park
Endocrinol Metab. 2021;36(2):447-454.   Published online March 31, 2021
  • 3,508 View
  • 127 Download
  • 8 Citations
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
Di-2-ethylhexyl phthalate (DEHP) is known to disrupt thyroid hormonal status. However, the underlying molecular mechanism of this disruption is unclear. Therefore, we investigated the direct effects of DEHP on the thyroid gland.
DEHP (vehicle, 50 mg/kg, and 500 mg/kg) was administered to Sprague-Dawley rats for 2 weeks. The expression of the thyroid hormone synthesis pathway in rat thyroid tissues was analyzed through RNA sequencing analysis, quantitative reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemical (IHC) staining. DEHP was treated to FRTL-5 rat thyroid cells, and an RT-PCR analysis was performed. A reporter gene assay containing the promoter of thyroid stimulating hormone receptor (TSHR) in Nthy-ori 3-1 human thyroid cells was constructed, and luciferase activity was determined.
After DEHP treatment, the free thyroxine (T4) and total T4 levels in rats significantly decreased. RNA sequencing analysis of rat thyroid tissues showed little difference between vehicle and DEHP groups. In the RT-PCR analysis, Tshr expression was significantly lower in both DEHP groups (50 and 500 mg/kg) compared to that in the vehicle group, and IHC staining showed that TSHR expression in the 50 mg/kg DEHP group significantly decreased. DEHP treatment to FRTL-5 cells significantly down-regulated Tshr expression. DEHP treatment also reduced luciferase activity in a reporter gene assay for TSHR.
Although overall genetic changes in the thyroid hormone synthesis pathway are not clear, DEHP exposure could significantly down-regulate Tshr expression in thyroid glands. Down-regulation of Tshr gene appears to be one of potential mechanisms of thyroid disruption by DEHP exposure.


Citations to this article as recorded by  
  • Intrauterine exposure to di(2-ethylhexyl) phthalate (DEHP) disrupts the function of the hypothalamus-pituitary-thyroid axis of the F1 rats during adult life
    Érica Kássia Sousa-Vidal, Guilherme Henrique, Renata Elen Costa da Silva, Caroline Serrano-Nascimento
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Drinking water disinfection byproduct iodoacetic acid affects thyroid hormone synthesis in Nthy-ori 3–1 cells
    Jingyi Xiao, Yujie Sha, Yuwen Huang, Kunling Long, Huan Wu, Yan Mo, Qiyuan Yang, Shengkun Dong, Qiang Zeng, Xiao Wei
    Ecotoxicology and Environmental Safety.2023; 257: 114926.     CrossRef
  • Di(2-ethylhexyl) phthalate (DEHP) and thyroid: biological mechanisms of interference and possible clinical implications
    Xueting Zhang, Wen Qi, Qi Xu, Xu Li, Liting Zhou, Lin Ye
    Environmental Science and Pollution Research.2022; 29(2): 1634.     CrossRef
  • The possible thyroid disruptive effect of di-(2-ethyl hexyl) phthalate and the potential protective role of selenium and curcumin nanoparticles: a toxicological and histological study
    Naima Abd El-Halim Sherif, Asmaa El-Banna, Rehab Ahmed Abdel-Moneim, Zahraa Khalifa Sobh, Manal Ibrahim Fathy Balah
    Toxicology Research.2022; 11(1): 108.     CrossRef
  • Environmental disruption of reproductive rhythms
    Marie-Azélie Moralia, Clarisse Quignon, Marine Simonneaux, Valérie Simonneaux
    Frontiers in Neuroendocrinology.2022; 66: 100990.     CrossRef
  • Endocrine-disruptor endpoints in the ovary and thyroid of adult female rats exposed to realistic doses of di-(2-ethylhexyl) phthalate
    Amel Jebara, Asma Beltifa, Guissepa Di Bella, Lotfi Mabrouk, Hedi Ben Mansour
    Journal of Water and Health.2022; 20(8): 1256.     CrossRef
  • The influence of sunitinib and sorafenib, two tyrosine kinase inhibitors, on development and thyroid system in zebrafish larvae
    Gang Wei, Cao-xu Zhang, Yu Jing, Xia Chen, Huai-dong Song, Liu Yang
    Chemosphere.2022; 308: 136354.     CrossRef
  • Role of estrogen receptors in thyroid toxicity induced by mono (2-ethylhexyl) phthalate via endoplasmic reticulum stress: An in vitro mechanistic investigation
    Qi Xu, Liting Zhou, Hyonju Ri, Xu Li, Xueting Zhang, Wen Qi, Lin Ye
    Environmental Toxicology and Pharmacology.2022; 96: 104007.     CrossRef

Endocrinol Metab : Endocrinology and Metabolism