School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563000, PR China.
School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563000, PR China.
Chem Biol Interact. 2024 Mar 1;391:110909. doi: 10.1016/j.cbi.2024.110909. Epub 2024 Feb 8.
Thyroid disease has been rapidly increasing, but its causes remain unclear. At present, many studies have focused on the relationship between environmental endocrine disruptors (EEDs) and the pathogenesis of thyroid disease. Herein, we summarize such studies exploring the effects of exposure to common EEDs on thyrotoxicosis, finding that EEDs appear to contribute to the pathogenesis of thyroid-related diseases such as thyroid cancer, goiter, thyroiditis, hyperthyroidism, and hypothyroidism. To explore this causative effect in detail, we have analyzed the following three aspects of how EEDs are believed to exert their impacts on the occurrence and development of thyroid disease: (1) damage to the thyroid tissue structure, including disrupted mitochondria and the stratification of thyroid follicular epithelial cells; (2) disruption of thyroid hormone signaling, including thyroid hormone synthesis and secretion disorders, destruction of normal function of the hypothalamus-pituitary-thyroid axis, disturbed estrogen signaling in the body, alterations to the level of thyroid-stimulating hormone, inhibition of the release of thyroglobulin from thyroid cells, and reductions in the levels of sodium iodide co-transporters, thyroid peroxidase, deiodinase, and transthyretin; and (3) molecular mechanisms underlying the disruption of thyroid function, including competitive binding to T3 and T4 receptors, disturbance of the hypothalamic-pituitary-thyroid axis, activation of the ERK and Akt pathways, oxidative stress, regulation of the expression of the proto-oncogene k-Ras, tumor suppressor gene PTEN, and thyroid TSHR gene, and induction of autophagy in thyroid cells. Overall, this article reviews how EEDs can affect the occurrence and development of thyroid disease via multiple routes, thus providing new ideas to intervene for the prevention, diagnosis, treatment, and prognosis of thyroid disease.
甲状腺疾病的发病率迅速上升，但病因仍不清楚。目前，许多研究集中在环境内分泌干扰物（EEDs）与甲状腺疾病发病机制的关系上。本文总结了这些研究，探讨了暴露于常见 EEDs 对甲状腺毒症的影响，发现 EEDs 似乎与甲状腺癌、甲状腺肿、甲状腺炎、甲状腺功能亢进和甲状腺功能减退等甲状腺相关疾病的发病机制有关。为了详细探讨这种因果关系，我们分析了 EEDs 如何影响甲状腺疾病发生和发展的三个方面：（1）甲状腺组织结构损伤，包括线粒体损伤和甲状腺滤泡上皮细胞分层；（2）甲状腺激素信号转导紊乱，包括甲状腺激素合成和分泌障碍、破坏下丘脑-垂体-甲状腺轴的正常功能、体内雌激素信号紊乱、促甲状腺激素水平改变、甲状腺球蛋白从甲状腺细胞释放受阻、钠碘同向转运体、甲状腺过氧化物酶、脱碘酶和转甲状腺素蛋白水平降低；（3）甲状腺功能紊乱的分子机制，包括与 T3 和 T4 受体的竞争性结合、下丘脑-垂体-甲状腺轴的干扰、ERK 和 Akt 通路的激活、氧化应激、原癌基因 k-Ras、肿瘤抑制基因 PTEN 和甲状腺 TSHR 基因表达的调节以及甲状腺细胞自噬的诱导。总之，本文综述了 EEDs 如何通过多种途径影响甲状腺疾病的发生和发展，为甲状腺疾病的预防、诊断、治疗和预后提供了新的思路。
