Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Chemosphere. 2020 Mar;243:125149. doi: 10.1016/j.chemosphere.2019.125149. Epub 2019 Nov 5.
Triphenyltin is an organotin, which is widely used as a fungicide in agriculture. Here, we reported the effects of triphenyltin on adrenal function in adult male rats. Adult male Sprague Dawley rats were daily gavaged with triphenyltin (0, 0.5, 1, and 2 mg/kg body weight) from postnatal day 56-86. Triphenyltin significantly decreased serum corticosterone levels at 1 and 2 mg/kg without affecting serum levels of aldosterone and adrenocorticotropic hormone. Triphenyltin increased thickness of zona glomerulosa without affecting that of zona fasciculata. Triphenyltin did not affect cell number in zona fasciculata and zona glomerulosa. Triphenyltin down-regulated the expression of Scarb1, Star, Cyp11a1, Hsd3b1, Cyp21, Cyp11b1, and Hsd11b1 at 1 and/or 2 mg/kg while it up-regulated the expression of At1, Nr4a2, and Hsd11b2 at 2 mg/kg. Triphenyltin activated the phosphorylation of AMPKα while suppressed the phosphorylation of AKT1 and SIRT1/PGC-1α in rat adrenals in vivo and H295R cells in vitro. In vitro, triphenyltin also induced ROS production in H295R cells at 100 nM, a concentration at which no apoptosis was induced. In conclusion, triphenyltin disrupts glucocorticoid synthesis in rat adrenal cortex via several mechanisms: 1) lowering AKT1 phosphorylation and SIRT1/PGC-1α levels; 2) activating AMPKα; and 3) possibly inducing ROS production.
三苯基锡是一种有机锡，广泛用作农业中的杀菌剂。在这里，我们报道了三苯基锡对成年雄性大鼠肾上腺功能的影响。成年雄性 Sprague Dawley 大鼠从出生后第 56-86 天每天灌胃三苯基锡（0、0.5、1 和 2mg/kg 体重）。三苯基锡在 1 和 2mg/kg 时显著降低血清皮质酮水平，而不影响醛固酮和促肾上腺皮质激素的血清水平。三苯基锡增加了肾小球带的厚度，而不影响束状带的厚度。三苯基锡不影响束状带和肾小球带的细胞数量。三苯基锡下调 Scarb1、Star、Cyp11a1、Hsd3b1、Cyp21、Cyp11b1 和 Hsd11b1 的表达，在 1 和/或 2mg/kg 时下调 At1、Nr4a2 和 Hsd11b2 的表达，在 2mg/kg 时上调 At1、Nr4a2 和 Hsd11b2 的表达。三苯基锡在体内激活 AMPKα的磷酸化，同时抑制 AKT1 和 SIRT1/PGC-1α 的磷酸化，在体内和 H295R 细胞中。在体外，三苯基锡还在 100nM 时诱导 H295R 细胞产生 ROS，在该浓度下不会诱导细胞凋亡。总之，三苯基锡通过几种机制破坏大鼠肾上腺皮质中的糖皮质激素合成：1）降低 AKT1 磷酸化和 SIRT1/PGC-1α 水平；2）激活 AMPKα；3）可能诱导 ROS 产生。
