Xu Renai, Shen Qiuxia, Li Senlin, Li Xiaojun, Li Huitao, Lü Yao, Lian Qing-Quan, Ge Ren-Shan
Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Chem Biol Interact. 2017 Jun 25;272:182-187. doi: 10.1016/j.cbi.2017.05.017. Epub 2017 May 20.
Perfluoroalkylated substances (PFASs), including perfluorooctyl sulphonate (PFOS) and perfluorooctane acid (PFOA), have been classified as persistent organic pollutants and are known to cause endocrine-disrupting effects in humans. The objective of the present study was to compare the potencies of four different PFASs, PFOS, PFOA, perfluorohexyl sulfonate (PFHxS), and perfluorobutyl sulfonate (PFBS), to inhibit neurosteroidogenic 5α-reductase 1 (SRD5A1), 3α-hydroxysteroid dehydrogenase (AKR1C9), and retinol dehydrogenase 2 (RoDH2) in rats. The potencies of PFASs to inhibit SRD5A1 are PFOS > PFOA > PFHxS = PFBS, with IC values of PFOS and PFOA of 1.92 ± 0.07 and 14.24 ± 0.07 μM and no effects for PFHxS and PFBS at 100 μM, respectively. The potencies of PFASs to inhibit AKR1C9 and RoDH2 are PFOS > PFOA > PFHxS = PFBS, with IC values of PFOS and PFOA on these two enzymes about 100 μM and no effects for PFHxS and PFBS at 100 μM, respectively. PFOS and PFOA competitively inhibited rat SRD5A1. In conclusion, PFOS and PFOA are potent inhibitors of rat SRD5A1, thereby controlling the biosynthesis of neurosteroids.
全氟烷基化物质（PFASs），包括全氟辛烷磺酸（PFOS）和全氟辛酸（PFOA），已被列为持久性有机污染物，并且已知会对人类产生内分泌干扰作用。本研究的目的是比较四种不同的PFASs，即PFOS、PFOA、全氟己烷磺酸（PFHxS）和全氟丁烷磺酸（PFBS），对大鼠神经甾体生成5α-还原酶1（SRD5A1）、3α-羟基类固醇脱氢酶（AKR1C9）和视黄醇脱氢酶2（RoDH2）的抑制能力。PFASs对SRD5A1的抑制能力为PFOS > PFOA > PFHxS = PFBS，PFOS和PFOA的IC值分别为1.92±0.07和14.24±0.07 μM，而PFHxS和PFBS在100 μM时无影响。PFASs对AKR1C9和RoDH2的抑制能力为PFOS > PFOA > PFHxS = PFBS，PFOS和PFOA对这两种酶的IC值约为100 μM，而PFHxS和PFBS在100 μM时无影响。PFOS和PFOA竞争性抑制大鼠SRD5A。总之，PFOS和PFOA是大鼠SRD5A的有效抑制剂，从而控制神经甾体的生物合成。
