title: Effects of Polybrominated Diphenyl Ethers on Rat and Human 11β-Hydroxysteroid Dehydrogenase 1 and 2 Activities.
abstract: Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants. PBDEs have been widely used in textiles, flexible polyurethane foams, electronic components, electrical components, and plastics. 11β-Hydroxysteroid dehydrogenases, isoform 1 (HSD11B1) and isoform 2 (HSD11B2), have been demonstrated to be the regulators of local glucocorticoid levels. In this study, the potencies of 4 different PBDEs (BDE-3, BDE-47, BDE-100, and BDE-153) with 1-6 bromine atoms attached in inhibition of rat and human HSD11B1 and HSD11B2 activities were compared to 4-bromobiphenyl (BBP), a structurally similar compound. All 4 PBDEs and BBP did not inhibit rat and human HSD11B1. BDE-3 and BDE-47 potently inhibited rat HSD11B2, and BDE-47 and BDE-153 potently inhibited human HSD11B2, with the half maximal inhibitory concentration values of 12.42, 5.95, 11.97, and 4.41 µmol/l, respectively. All PBDEs noncompetitively inhibited HSD11B2 when a steroid substrate was used. However, PBDEs exerted uncompetitive inhibition when the cofactor NAD+ was used. In conclusion, some PBDEs are selective inhibitors of HSD11B2, possibly causing excessive glucocorticoid action in local tissues.
authors.affiliation: Center of Scientific Research, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, PR China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Chen
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Dong
authors.forename: Shuyan
authors.initials: S
authors.lastname: Cao
authors.forename: Xiaoheng
authors.initials: X
authors.lastname: Li
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Ruijie
authors.initials: R
authors.lastname: Chen
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005411:Flame Retardants / Q000494:pharmacology*; D055768:Halogenated Diphenyl Ethers / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; C511295:2,2',4,4'-tetrabromodiphenyl ether; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D042842:11-beta-Hydroxysteroid Dehydrogenases; C468386:HSD11B1 protein, human; C468387:HSD11B2 protein, human