The inhibition of human and rat 11β-hydroxysteroid dehydrogenase 2 by perfluoroalkylated substances

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• 作者：Binghai Zhao^a ; ^b ; Qingquan Lian^c ; Yanhui Chu^a ; Dianne O. Hardy^b ; Xiao-Kun Li^d ; ^{xiaokunli@163.net"" rel=""nofollow} ; Ren-Shan Ge^b ; ^c ; ^{rge@popcbr.rockefeller.edu"" rel=""nofollow}
• 关键词：11β ; -Hydroxysteroid dehydrogenase 2 ; Human kidney ; Perfluorinated substances ; Perfluoroalkyl acids ; Perfluorooctyl sulphonate ; Perfluorohexyl sulfonate ; Perfluorobutyl sulphonate ; Perfluorooctanoic acid
• 刊名：The Journal of Steroid Biochemistry and Molecular Biology
• 出版年：2011
• 出版时间：May 2011
• 年：2011
• 卷：125
• 期：1-2
• 页码：143-147
• 全文大小：294 K

文摘

11β-Hydroxysteroid dehydrogenase 2 (11β-HSD2) regulates active glucocorticoid access to glucocorticoid and mineralocorticoid receptors by metabolizing it to an inactive form. Perfluoroalkylated substances (PFASs) are man-made polyfluorinated compounds that are widely used and persistent in the environment. We tested the inhibitory potencies of four PFASs including perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexanesulfonate (PFHxS) and perfluorobutane sulfonate (PFBS) on human and rat 11β-HSD2. PFOS was a potent inhibitor of both human (IC₅₀ = 48 nM) and rat (IC₅₀ = 293 nM) 11β-HSD2 activities. The potencies for the inhibition of human and rat 11β-HSD2 activities were PFOS > PFOA > PFHxS > PFBS. PFASs showed competitive inhibition of both human and rat 11β-HSD2 activities. This observation indicates that PFOS is a potent endocrine disruptor for glucocorticoid metabolism.

Article from the Special issue on Targeted Inhibitors.