The Effects of Disturbance on Hypothalamus-Pituitary-Thyroid (HPT) Axis in Zebrafish Larvae after Exposure to DEHP
The Effects of Disturbance on Hypothalamus-Pituitary-Thyroid (HPT) Axis in Zebrafish Larvae after Exposure to DEHP
复制标题
DEHP 干扰对斑马鱼幼虫下丘脑-垂体-甲状腺 (HPT) 轴的影响
DOI：
10.1371/journal.pone.0155762
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发表时间：
2016-05-25
期刊：
影响因子：
3.7
通讯作者：
Pei, De-Sheng
中科院分区：
文献类型：
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作者：
Jia, Pan-Pan;Ma, Yan-Bo;Pei, De-Sheng
邻苯二甲酸二(2-乙基己基)酯 (DEHP) 有可能破坏甲状腺内分泌系统，但其潜在机制尚不清楚。在这项研究中，斑马鱼 (Danio rerio) 胚胎在受精后 2 至 168 小时 (hpf) 期间暴露于不同浓度的 DEHP（0、40、100、200、400 μg/L）。检查了甲状腺激素（THs）水平和与下丘脑-垂体-甲状腺（HPT）轴相关的关键基因的转录谱。全身甲状腺素(T4)和三碘甲状腺原氨酸(T3)的结果表明DEHP破坏了斑马鱼幼虫的甲状腺激素稳态。暴露于 DEHP 后，促甲状腺激素 (tsh beta) 和促肾上腺皮质激素释放激素 (crh) 基因的 mRNA 表达分别以浓度依赖性方式增加。还测量了涉及甲状腺发育（nkx2.1 和 pax8）和甲状腺合成（钠/碘同向转运蛋白、nis、甲状腺球蛋白、tg）的基因的表达水平。 DEHP暴露后nkx2.1和tg的转录本显着增加，而nis和pax8的转录本没有显着变化。尿苷二磷酸葡萄糖醛酸基转移酶 (ugt1ab) 的下调和甲状腺氨酸脱碘酶 (dio2) 的上调可能会改变 THs 水平。此外，转甲状腺素蛋白（ttr）的转录本上调，而甲状腺激素受体（tr α和tr β）的mRNA水平保持不变。所有结果表明，DEHP暴露改变了斑马鱼幼虫全身甲状腺激素，并改变了与HPT轴相关的关键基因的表达谱，证明DEHP诱导了甲状腺内分泌毒性，并可能影响甲状腺激素的合成、调节和作用。
Di-(2-ethylhexyl) phthalate (DEHP) has the potential to disrupt the thyroid endocrine system, but the underlying mechanism is unknown. In this study, zebrafish (Danio rerio) embryos were exposed to different concentrations of DEHP (0, 40, 100, 200, 400 mu g/L) from 2 to 168 hours post fertilization (hpf). Thyroid hormones (THs) levels and transcriptional profiling of key genes related to hypothalamus-pituitary-thyroid (HPT) axis were examined. The result of whole-body thyroxine (T4) and triiodothyronine (T3) indicated that the thyroid hormone homeostasis was disrupted by DEHP in the zebrafish larvae. After exposure to DEHP, the mRNA expressions of thyroid stimulating hormone (tsh beta) and corticotrophin releasing hormone (crh) genes were increased in a concentration dependent manner, respectively. The expression level of genes involved in thyroid development (nkx2.1 and pax8) and thyroid synthesis (sodium/iodide symporter, nis, thyroglobulin, tg) were also measured. The transcripts of nkx2.1 and tg were significantly increased after DEHP exposure, while those of nis and pax8 had no significant change. Down-regulation of uridinediphosphate-glucuronosyl-transferase (ugt1ab) and up-regulation of thyronine deiodinase (dio2) might change the THs levels. In addition, the transcript of transthyretin (ttr) was up-regulated, while the mRNA levels of thyroid hormone receptors (tr alpha and tr beta) remained unchanged. All the results demonstrated that exposure to DEHP altered the whole-body thyroid hormones in the zebrafish larvae and changed the expression profiling of key genes related to HPT axis, proving that DEHP induced the thyroid endocrine toxicity and potentially affected the synthesis, regulation and action of thyroid hormones.