Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China.
Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China.
Food Chem Toxicol. 2020 Sep;143:111479. doi: 10.1016/j.fct.2020.111479. Epub 2020 Jun 3.
Triphenyltin has been classified as an endocrine disruptor. However, whether triphenyltin interferes with the adrenal glands during puberty remains unknown. Here, we reported the effects of triphenyltin on the adrenal glands in rats. Male Sprague Dawley rats (age of 35 days) were orally administered with 0, 0.5, 1, or 2 mg/kg/day triphenyltin for 18 days. Triphenyltin significantly lowered corticosterone levels at 1 and 2 mg/kg and adrenocorticotropic hormone at 2 mg/kg. The RNA-Seq analysis detected multiple differentially expressed genes. Four down-regulated genes were transcription factor genes (Nr4a1, Nr4a2, Nr4a3, and Ppard), which might be associated with the suppression of the adrenal cortex function. RNA-seq and qPCR showed that triphenyltin dose-dependently down-regulated the expression of the genes for cholesterol transport and biosynthesis, including Scarb1, Ldlr, Hmgcs1, Hmgcr, and Hsd17b7. Further Western blotting revealed that it lowered NR4A1, PPRAD, LDLR, and HMGCS1 protein levels. We treated H295R adrenal cells with 1-100 nM triphenyltin for 72 h. Triphenyltin induced significant higher ROS production at 100 nM and did not induce apoptosis at 10 and 100 nM. In conclusion, triphenyltin inhibits production of corticosterone via blocking the expression of cholesterol uptake transporters and cholesterol biosynthesis.
三苯基锡已被归类为一种内分泌干扰物。然而，三苯基锡是否在青春期干扰肾上腺尚不清楚。在这里，我们报道了三苯基锡对大鼠肾上腺的影响。雄性 Sprague Dawley 大鼠（35 天大）经口给予 0、0.5、1 或 2 mg/kg/天三苯基锡，连续 18 天。三苯基锡在 1 和 2 mg/kg 时显著降低皮质酮水平，在 2 mg/kg 时降低促肾上腺皮质激素水平。RNA-Seq 分析检测到多个差异表达基因。四个下调的基因是转录因子基因（Nr4a1、Nr4a2、Nr4a3 和 Ppard），它们可能与肾上腺皮质功能的抑制有关。RNA-seq 和 qPCR 显示，三苯基锡呈剂量依赖性地下调胆固醇转运和生物合成基因的表达，包括 Scarb1、Ldlr、Hmgcs1、Hmgcr 和 Hsd17b7。进一步的 Western blot 显示，它降低了 NR4A1、PPRAD、LDLR 和 HMGCS1 蛋白水平。我们用 1-100 nM 三苯基锡处理 H295R 肾上腺细胞 72 小时。三苯基锡在 100 nM 时诱导显著更高的 ROS 产生，在 10 和 100 nM 时不诱导细胞凋亡。总之，三苯基锡通过阻断胆固醇摄取转运体和胆固醇生物合成的表达来抑制皮质酮的产生。
