The inhibition of human and rat 11β-hydroxysteroid dehydrogenase 2 by perfluoroalkylated substances.
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 (IC(50)=48 nM) and rat (IC(50)=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.
Heilongjiang Key Laboratory of Anti-fibrosis Biotherapy, Mudanjiang Medical University, Heilongjiang 157011, PR China.
Binghai
B
Zhao
Qingquan
Q
Lian
Yanhui
Y
Chu
Dianne O
DO
Hardy
Xiao-Kun
XK
Li
Ren-Shan
RS
Ge
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D052244:Endocrine Disruptors / Q000737:chemistry / Q000378:metabolism; D005466:Fluorocarbons / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D015394:Molecular Structure; D051381:Rats
D052244:Endocrine Disruptors; D005466:Fluorocarbons; D007527:Isoenzymes; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2