ArticleScientific reports2017
Di2-ethylhexyl phthalate disrupts thyroid hormone homeostasis through activating the Ras/Akt/TRHr pathway and inducing hepatic enzymes.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 113 citations in OpenAlex.
- Article
- Associations between environmental phthalates exposure and maternal thyroid hormone levels during pregnancy.Archives of toxicology · 2025Article
- Review
- Review
- Hidden link between endocrine-disrupting chemicals and pediatric obesity.Clinical and experimental pediatrics · 2025Article
- Phthalates toxicityHeliyon · 2025Article
- Intergenerational and transgenerational effects of endocrine-disrupting chemicals in the offspring brain development and behavior.Frontiers in endocrinology · 2025Review
- Network toxicological insights into DEHP exposure and thyroid cancer development and progression.Frontiers in oncology · 2025Article
- Effects of endocrine disruptors on the neurological system.Turkish journal of medical sciences · 2025Review
- 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
- Confirmation of Di(2-ethylhexyl) phthalate-induced micronuclei by repeated dose liver micronucleus assay: focus on evaluation of liver micronucleus assay in young rats.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2024Article
- Thyroid Hormone Biomonitoring: A Review on Their Metabolism and Machine-Learning Based Analysis on Effects of Endocrine Disrupting Chemicals.Environment & health (Washington, D.C.) · 2024Review
- Association of diethylhexyl phthalate exposure with serum thyroid hormone levels: a systematic review and meta-analysis.American journal of translational research · 2024Review
- Long-term exposure to exogenous phthalate, masculinity and femininity trait, and gender identity in children: a Chinese 3-year longitudinal cohort study.Environmental health : a global access science source · 2023Article
- DEHP exposure impairs human skeletal muscle cell proliferation in primary culture conditions: preliminary study.Cytotechnology · 2023Article
- Daily exposure to low concentrations Tetrabromobisphenol A interferes with the thyroid hormone pathway in HepG2 cells.Fundamental research · 2023Article
- Major contaminants of emerging concern in soils: a perspective on potential health risks.RSC advances · 2022Review
- Risk of Nonalcoholic Fatty Liver Disease Is Associated with Urinary Phthalate Metabolites Levels in Adults with Subclinical Hypothyroidism: Korean National Environmental Health Survey (KoNEHS) 2012-2014.International journal of environmental research and public health · 2022Article
- The associations of urinary DEHP metabolite levels, serum thyroid hormones, and thyroid-related genes among the adolescent students from China: a cross-sectional study.Environmental science and pollution research international · 2022Article
- 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
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Di(2-ethylhexyl) phthalate (DEHP), as a widespread environmental pollutant and an endocrine disruptor, can disturb the homeostasis of thyroid hormones (THs). In order to elucidate roles of the MAPK and PI3K/Akt pathways and hepatic enzymes in thyroid-disrupting effects of DEHP, Sprague-Dawley rats were dosed with DEHP by gavage for 30 consecutive days; Nthy-ori 3-1 cells were treated with DEHP with NAC, k-Ras siRNA or inhibitors (U0126 and wortmannin). Results showed that DEHP led to histopathologic changes in rat thyroid and liver, such as the decrease in thyroid follicular cavity diameter, hepatocyte edema. Triiodothyronine (T3), thyroxine (T4) and thyrotropin releasing hormone (TRH) were reduced. DEHP caused ROS production, oxidative stress and k-Ras upregulation, thereby activating the ERK and Akt pathways in vivo and in vitro. Moreover, TRH receptor (TRHr) level was elevated after the activation of the Akt pathway and was downregulated after the inhibition of the Akt pathway. However, TRHr was not modulated by the ERK pathway. Additionally, hepatic enzymes, including Ugt1a1, CYP2b1, Sult1e1, and Sult2b1, were significantly induced after DEHP exposure. Taken together, DEHP can perturb TH homeostasis and reduce TH levels. The activated Ras/Akt/TRHr pathway and induced hepatic enzymes play vital roles in thyroid-disrupting effects of DEHP.
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