Department of Environmental Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Mol Med Rep. 2021 Apr;23(4). doi: 10.3892/mmr.2021.11930. Epub 2021 Mar 2.
Di (2‑ethylhexyl) phthalate (DEHP), an environmental pollutant, is widely used as a plasticizer and causes serious pollution in the ecological environment. As previously reported, exposure to DEHP may cause thyroid dysfunction of the hypothalamic‑pituitary‑thyroid (HPT) axis. However, the underlying role of DEHP remains to be elucidated. The present study performed intragastrical administration of DEHP (150, 300 and 600 mg/kg) once a day for 90 consecutive days. DEHP‑stimulated oxidative stress increased the thyroid follicular cavity diameter and caused thyrocyte oedema. Furthermore, DEHP exposure altered mRNA and protein levels. Thus, DEHP may perturb TH homeostasis by affecting biosynthesis, biotransformation, bio‑transportation, receptor levels and metabolism through disruption of the HPT axis and activation of the thyroid‑stimulating hormone (TSH)/TSH receptor signaling pathway. These results identified the formerly unappreciated endocrine‑disrupting activities of phthalates and the molecular mechanisms of DEHP‑induced thyrotoxicity.
邻苯二甲酸二（2-乙基己基）酯（DEHP）作为一种环境污染物，被广泛用作增塑剂，对生态环境造成严重污染。据先前报道，接触 DEHP 可能导致下丘脑-垂体-甲状腺（HPT）轴的甲状腺功能障碍。然而，DEHP 的潜在作用仍有待阐明。本研究通过灌胃给予 DEHP（150、300 和 600mg/kg），每天 1 次，连续 90 天。DEHP 刺激的氧化应激增加了甲状腺滤泡腔直径，并导致甲状腺细胞水肿。此外，DEHP 暴露改变了 mRNA 和蛋白质水平。因此，DEHP 可能通过破坏 HPT 轴和激活促甲状腺激素（TSH）/TSH 受体信号通路，影响生物合成、生物转化、生物转运、受体水平和代谢，从而扰乱 TH 稳态。这些结果确定了邻苯二甲酸酯以前未被认识到的内分泌干扰活性和 DEHP 诱导的甲状腺毒性的分子机制。
