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.

三苯基锡已被分类为内分泌干扰物。然而，在青春期三苯基锡是否会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（年龄35天）口服给予0、0.5、1或2 mg / kg /天的三苯基锡18天。三苯基锡显着降低了1和2 mg / kg的皮质酮水平，以及2 mg / kg的促肾上腺皮质激素。RNA-Seq分析检测到多个差异表达的基因。四个下调的基因是转录因子基因（Nr4a1，Nr4a2，Nr4a3和Ppard），可能与抑制肾上腺皮质功能有关。RNA-seq和qPCR显示，三苯基锡剂量依赖性地下调了胆固醇转运和生物合成基因的表达，包括Scarb1，Ldlr，Hmgcs1，Hmgcr和Hsd17b7。进一步的蛋白质印迹显示它降低了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时诱导明显更高的ROS产生，在10和100 nM时不诱导凋亡。总之，三苯基锡通过阻断胆固醇摄取转运蛋白的表达和胆固醇的生物合成来抑制皮质酮的产生。