Fipronil is a phenylpyrazole insecticide used for the control of a variety of pest for domestic, veterinary and agricultural uses. Fipronil exposure is associated to thyroid disruption in the rat. It increases thyroid hormone (TH) hepatic clearance. The effect on thyroxine (T4) clearance is about four fold higher than the effect on T4 plasma concentrations suggesting that the thyroid gland might develop compensatory mechanisms. The aim of this study was to document the potential effects of fipronil treatment on the thyroid transcriptome together with its effects on TSH and TH blood levels under well characterized internal exposure to fipronil and its main metabolite fipronil sulfone. Fipronil (3 mg/kg/d by gavage for 14 days) clearance increased while its half-life decreased (about 10 fold) throughout treatment. Fipronil treatment in adult female rats significantly decreased total T4 and free triiodothyronine (T3) concentrations. Key genes related to thyroid hormone synthesis and/or cellular dynamic were modulated by fipronil exposure. RT-PCR confirmed that thyroglobulin gene expression was upregulated. A trend toward higher Na/I symporter expression was also noted, while sulfotransferase 1a1 gene expression was down-regulated. The expression of genes potentially involved in thyroid cell dynamic were upregulated (e.g. prostaglandin synthase 1, amphiregulin and Rhoa). Our results indicate that both pathways of TH synthesis and thyroid cell dynamics are transcriptional targets of fipronil and/or its main sulfone metabolite. The underlying mechanisms remain to be elucidated.

中文翻译：

---

暴露于植物检疫级氟虫腈的甲状腺的转录组修饰：补偿性途径激活的证据。

Fipronil是一种苯基吡唑类杀虫剂，用于控制家庭，兽医和农业使用的各种害虫。Fipronil暴露与大鼠甲状腺功能紊乱有关。它会增加甲状腺激素（TH）的肝清除率。对甲状腺素（T4）清除的影响比对T4血浆浓度的影响高约四倍，这表明甲状腺可能会发展代偿机制。这项研究的目的是证明在特征明确的内部暴露于氟虫腈及其主要代谢物氟虫腈砜的情况下，氟虫腈治疗对甲状腺转录组的潜在影响以及对TSH和TH血药水平的影响。在整个治疗过程中，Fipronil（3 mg / kg / d通过管饲法治疗14天）清除率增加，而其半衰期减少（约10倍）。成年雌性大鼠中的Fipronil治疗显着降低了总T4和游离三碘甲状腺素（T3）的浓度。氟虫腈暴露可调节与甲状腺激素合成和/或细胞动力学有关的关键基因。RT-PCR证实甲状腺球蛋白基因表达上调。还注意到了Na / I同向转运体表达增加的趋势，而磺基转移酶1a1基因的表达被下调。可能参与甲状腺细胞动力学的基因的表达上调（例如前列腺素合酶1，双调蛋白和Rhoa）。我们的结果表明TH合成和甲状腺细胞动力学的通路都是氟虫腈和/或其主要砜代谢产物的转录靶标。潜在的机制尚待阐明。氟虫腈暴露可调节与甲状腺激素合成和/或细胞动力学有关的关键基因。RT-PCR证实甲状腺球蛋白基因表达上调。还注意到了Na / I同向转运体表达增加的趋势，而磺基转移酶1a1基因的表达被下调。可能参与甲状腺细胞动力学的基因的表达上调（例如前列腺素合酶1，双调蛋白和Rhoa）。我们的结果表明TH合成和甲状腺细胞动力学的通路都是氟虫腈和/或其主要砜代谢产物的转录靶标。潜在的机制尚待阐明。氟虫腈暴露可调节与甲状腺激素合成和/或细胞动力学有关的关键基因。RT-PCR证实甲状腺球蛋白基因表达上调。还注意到了Na / I同向转运体表达增加的趋势，而磺基转移酶1a1基因的表达被下调。可能参与甲状腺细胞动力学的基因的表达上调（例如前列腺素合酶1，双调蛋白和Rhoa）。我们的结果表明TH合成和甲状腺细胞动力学的通路都是氟虫腈和/或其主要砜代谢产物的转录靶标。潜在的机制尚待阐明。还注意到了Na / I同向转运体表达增加的趋势，而磺基转移酶1a1基因的表达被下调。可能参与甲状腺细胞动力学的基因的表达上调（例如前列腺素合酶1，双调蛋白和Rhoa）。我们的结果表明TH合成和甲状腺细胞动力学的通路都是氟虫腈和/或其主要砜代谢产物的转录靶标。潜在的机制尚待阐明。还注意到了Na / I同向转运体表达增加的趋势，而磺基转移酶1a1基因的表达被下调。可能参与甲状腺细胞动力学的基因的表达上调（例如前列腺素合酶1，双调蛋白和Rhoa）。我们的结果表明TH合成和甲状腺细胞动力学的通路都是氟虫腈和/或其主要砜代谢产物的转录靶标。潜在的机制尚待阐明。我们的结果表明TH合成和甲状腺细胞动力学的通路都是氟虫腈和/或其主要砜代谢产物的转录靶标。潜在的机制尚待阐明。我们的结果表明TH合成和甲状腺细胞动力学的通路都是氟虫腈和/或其主要砜代谢产物的转录靶标。潜在的机制尚待阐明。