Long-term triphenyltin exposure disrupts adrenal function in adult male rats. (March 2020)

• Record Type: Journal Article
• Authors: Wu, Keyang; Li, Yang; Liu, Jianpeng; Mo, Jiaying; Li, Xiaoheng; Ge, Ren-shan
• Is Part Of: Chemosphere. Volume 243(2020)
• Publication Date: 2020-03
• Subjects: Triphenyltin -- Adrenal cortex -- Adrenal function -- Gene expression -- Steroidogenesis; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2019.125149
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: Triphenyltin inhibits corticosterone synthesis in rat adrenals. Triphenyltin down-regulates steroidogenesis-related gene expression. Triphenyltin increases the thickness of the zG in rat adrenals.