Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro.
Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro.
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DOI：
10.1371/journal.pone.0151192
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Feldt-Rasmussen U
中科院分区：
文献类型：
--
作者：
Hansen JF;Brorson MM;Boas M;Frederiksen H;Nielsen CH;Lindström ES;Hofman-Bang J;Hartoft-Nielsen ML;Frisch T;Main KM;Bendtzen K;Rasmussen ÅK;Feldt-Rasmussen U
邻苯二甲酸盐是添加到多种产品中的增塑剂，导致人类大量接触邻苯二甲酸盐。由于流行病学研究表明它们对外周甲状腺激素浓度有影响，因此怀疑它们会破坏甲状腺轴。该机制仍不清楚，因为该领域的体外研究很少。本研究的目的是探讨三种邻苯二甲酸二酯（邻苯二甲酸二乙酯、邻苯二甲酸二正丁酯（DnBP）、邻苯二甲酸二（2-乙基己）酯（DEHP））和两种单酯（邻苯二甲酸单正丁酯和邻苯二甲酸单（2-乙基己）酯（MEHP））对原代人甲状腺细胞培养物分化功能的影响。此外，还研究了邻苯二甲酸酯代谢动力学。 DEHP及其单酯MEHP均对细胞分泌3'-5'-环单磷酸腺苷有抑制作用，MEHP还对细胞分泌甲状腺球蛋白(Tg)有抑制作用。乳酸脱氢酶测量结果表明 MEHP 介导的影响是由细胞死亡引起的。任何所研究的二酯均未证明对甲状腺特异性基因（Tg、甲状腺过氧化物酶、钠碘同向转运蛋白和促甲状腺激素受体）的基因表达有影响。所有邻苯二甲酸酯二酯均代谢为各自的单酯，但高浓度的较大二酯 DnBP 和 DEHP 的效率会下降。总之，人类甲状腺细胞能够代谢邻苯二甲酸盐，但这种邻苯二甲酸盐暴露似乎并没有显着影响这些细胞的选定功能。
Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP)) and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate (MEHP)) on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3'-5'-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg) secretion from the cells. Results of the lactate dehydrogenase-measurements indicated that the MEHP-mediated influence was caused by cell death. No influence on gene expression of thyroid specific genes (Tg, thyroid peroxidase, sodium iodine symporter and thyroid stimulating hormone receptor) by any of the investigated diesters could be demonstrated. All phthalate diesters were metabolised to the respective monoester, however with a fall in efficiency for high concentrations of the larger diesters DnBP and DEHP. In conclusion, human thyroid cells were able to metabolise phthalates but this phthalate-exposure did not appear to substantially influence selected functions of these cells.