ArticleEndocrinology and metabolism (Seoul, Korea)2021
DEHP Down-Regulates Tshr Gene Expression in Rat Thyroid Tissues and FRTL-5 Rat Thyrocytes: A Potential Mechanism of Thyroid Disruption.
Article in Endocrinology and metabolism (Seoul, Korea), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Assessment of five typical environmental endocrine disruptors and thyroid cancer risk: a meta-analysis.Frontiers in endocrinology · 2023Pooled it
- Fructose impairs brown adipogenesis by promoting thyroid hormone resistance in differentiated brown adipocytes.Biology open · 2026Article
- Oral Intake of Plasticizer Di-(2-ethylhexyl) Phthalate Disrupts Cerebellar Myelination via Thyroid Signaling in Aging Mice.Environment & health (Washington, D.C.) · 2025Article
- Polystyrene Microplastics-Induced Thyroid Dysfunction in Mice: A Study of Gene Expression, Oxidative Stress, and Histopathological Changes.Veterinary medicine and science · 2025Article
- Maternal Thyroid Hormones as Mediators between Phthalate Exposure and Neonatal Birth Weight: A Cross-Sectional Study from the Zunyi Birth Cohort.Environment & health (Washington, D.C.) · 2024Article
- Investigation of the effects of phthalates onFrontiers in endocrinology · 2023Article
- 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.Toxicology research · 2022Article
- Di(2-ethylhexyl) phthalate (DEHP) and thyroid: biological mechanisms of interference and possible clinical implications.Environmental science and pollution research international · 2022Review
- Intrauterine exposure to di(2-ethylhexyl) phthalate (DEHP) disrupts the function of the hypothalamus-pituitary-thyroid axis of the F1 rats during adult life.Frontiers in endocrinology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDi-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.
methodsDEHP (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.
resultsAfter 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.
conclusionAlthough 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.
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