Perfluorotetradecanoic acid (PFTeDA) is a novel perfluoroalkyl substance that ubiquitously exists in the environment. However, whether PFTeDA affects adrenal cortex function remains unclear. Male Sprague–Dawley rats (age of 60 days) were daily administered with PFTeDA (0, 1, 5, and 10 mg/kg body weight) through gavage for 28 days. PFTeDA did not change body and adrenal gland weights. PFTeDA markedly elevated serum corticosterone level at 10 mg/kg but lowering serum aldosterone level at this dosage without influencing serum adrenocorticotropic hormone level. PFTeDA thickened zona fasciculata without affecting zona glomerulosa. PFTeDA remarkably upregulated the expression of corticosterone biosynthetic genes (Mc2r, Scarb1, Star, Cyp21, Cyp11b1, and Hsd11b1) and their proteins, whereas downregulating aldosterone biosynthetic enzyme Cyp11b2 and its protein, thereby distinctly altering their serum levels. PFTeDA markedly downregulated the expression of antioxidant genes (Sod1 and Sod2) and their proteins at 10 mg/kg. PFTeDA significantly decreased SIRT1/PGC1α and AMPK signaling while stimulating AKT1/mTOR signaling. Corticosterone significantly inhibited testosterone production by adult Leydig cells at >0.1 μM in vitro; however aldosterone significantly stimulated testosterone production at 0.1 nM. In conclusion, exposure to PFTeDA at male rat adulthood causes corticosterone excess and aldosterone deficiency via SIRT1/PGC1α, AMPK, and AKT1/mTOR signals, which in turn additively leads to testosterone deficiency.

中文翻译：

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成年雄性大鼠接触全氟十四烷酸会刺激皮质酮生物合成，但抑制醛固酮产生

全氟十四烷酸（PFTeDA）是一种新型全氟烷基物质，广泛存在于环境中。然而，PFTeDA 是否影响肾上腺皮质功能仍不清楚。雄性 Sprague-Dawley 大鼠（60 天）每天通过灌胃法给予 PFTeDA（0、1、5 和 10 mg/kg 体重），持续 28 天。 PFTeDA 不会改变身体和肾上腺的重量。 PFTeDA 在 10 mg/kg 剂量下显着升高血清皮质酮水平，但在该剂量下降低血清醛固酮水平，而不影响血清促肾上腺皮质激素水平。 PFTeDA 增厚束状带而不影响肾小球带。 PFTeDA显着上调皮质酮生物合成基因（ Mc2r、Scarb1、Star、Cyp21、Cyp11b1和Hsd11b1 ）及其蛋白质的表达，同时下调醛固酮生物合成酶Cyp11b2及其蛋白质的表达，从而显着改变其血清水平。 PFTeDA 在 10 mg/kg 浓度下显着下调抗氧化基因（ Sod1和Sod2）及其蛋白质的表达。 PFTeDA 显着降低 SIRT1/PGC1α 和 AMPK 信号传导，同时刺激 AKT1/mTOR 信号传导。体外，皮质酮在 >0.1 μM 时显着抑制成年 Leydig 细胞产生睾酮；然而，0.1 nM 的醛固酮可显着刺激睾酮的产生。总之，成年雄性大鼠接触 PFTeDA 通过 SIRT1/PGC1α、AMPK 和 AKT1/mTOR 信号导致皮质酮过量和醛固酮缺乏，进而导致睾酮缺乏。