The inhibitory effects of perfluoroalkyl substances on human and rat 11¦Â-hydroxysteroid dehydrogenase 1

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• 作者：Leping Ye^a ; ^b ; Binghai Zhao^c ; Xiao-Hong Cai^a ; Yanhui Chu^c ; Changchong Li^a ; ^{wzlichch@21cn.com} ; Ren-Shan Ge^a ; ^b ; ^{rge@popcbr.rockefeller.edu}
• 关键词：11¦ÂHSD1 ; 11¦Â-hydroxysteroid dehydrogenase 1 ; 11DHC ; 11-dehydrocorticosterone ; CORT ; corticosterone ; G6P ; glucose-6-phosphate ; PFAS ; perfluoroalkyl substance ; PFOS ; perfluorooctane sulfonic acid ; PFOA ; perfluorooctanoic acid ; PFBS ; potassium perfluorobut
• 刊名：Chemico-Biological Interactions
• 出版年：2012
• 出版时间：25 January 2012
• 年：2012
• 卷：195
• 期：2
• 页码：114-118
• 全文大小：334 K

文摘

Perfluoroalkyl substances (PFASs) are man-made polyfluorinated compounds that are widely used and persistent in the environment. PFASs have potential effects on many biological systems including the development of lung. Glucocorticoids have been reported to promote fetal and neonatal lung development at the late stage, and 11¦Â-hydroxysteroid dehydrogenase 1(11¦ÂHSD1) in the lung is critical for the generation of local active glucocorticoid cortisol (human) or corticosterone (rodents) from biologically inert 11keto-steroids. The purpose of the present study is to study the direct inhibitory effects of PFASs on 11¦ÂHSD1 activities and action modes. Microsomal 11¦ÂHSD1 was subjected to the exposure to various PFASs, including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), potassium perfluorohexanesulfonate (PFHxS) and potassium perfluorobutane sulfonate (PFBS). PFOS and PFOA inhibited neonatal rat lung 11¦ÂHSD1 activity with IC₅₀s of 3.45 ¦ÌM (95 % Confidence Intervals, CI₉₅: 1.97-6.37 ¦ÌM) and 45.31 ¦ÌM (CI₉₅: 27.64-74.26 ¦ÌM), respectively, while PFHxS and PFBS did not inhibit the enzyme activity at 250 ¦ÌM. PFOS and PFOA inhibited human 11¦ÂHSD1 activity with IC₅₀s of 7.56 ¦ÌM (CI₉₅: 2.86-19.97 ¦ÌM) and 37.61 ¦ÌM (CI₉₅: 24.49-57.75 ¦ÌM), respectively, while PFHxS and PFBS did not inhibit the enzyme activity at 250 ¦ÌM. PFASs showed competitive inhibition on both human and rat 11¦ÂHSD1. In conclusion, the present study shows that PFOS and PFOA are the inhibitors of 11¦ÂHSD1.