title: The inhibitory effects of perfluoroalkyl substances on human and rat 11β-hydroxysteroid dehydrogenase 1.
abstract: 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 11β-hydroxysteroid dehydrogenase 1(11βHSD1) 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 11βHSD1 activities and action modes. Microsomal 11βHSD1 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 11βHSD1 activity with IC(50)s of 3.45μM (95% Confidence Intervals, CI(95): 1.97-6.37μM) and 45.31μM (CI(95): 27.64-74.26μM), respectively, while PFHxS and PFBS did not inhibit the enzyme activity at 250μM. PFOS and PFOA inhibited human 11βHSD1 activity with IC(50)s of 7.56μM (CI(95): 2.86-19.97μM) and 37.61μM (CI(95): 24.49-57.75μM), respectively, while PFHxS and PFBS did not inhibit the enzyme activity at 250μM. PFASs showed competitive inhibition on both human and rat 11βHSD1. In conclusion, the present study shows that PFOS and PFOA are the inhibitors of 11βHSD1.
authors.affiliation: The 2nd Affiliated Hospital, Affiliated Yuying Children's Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, PR China.
authors.forename: Leping
authors.initials: L
authors.lastname: Ye
authors.forename: Binghai
authors.initials: B
authors.lastname: Zhao
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Cai
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Chu
authors.forename: Changchong
authors.initials: C
authors.lastname: Li
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000476:Alkanesulfonates / Q000494:pharmacology*; D017738:Alkanesulfonic Acids / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002210:Caprylates / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005466:Fluorocarbons / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051381:Rats; D013451:Sulfonic Acids / Q000494:pharmacology
chemical_list: D000476:Alkanesulfonates; D017738:Alkanesulfonic Acids; D002210:Caprylates; D004791:Enzyme Inhibitors; D005466:Fluorocarbons; D013451:Sulfonic Acids; C542778:nonafluorobutane-1-sulfonic acid; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid; D042842:11-beta-Hydroxysteroid Dehydrogenases