title: Zearalenone Inhibits Rat and Human 11β-Hydroxysteroid Dehydrogenase Type 2.
abstract: Zearalenone is a mycotoxin produced by Fusarium spp. 11β-Hydroxysteroid dehydrogenases, isoforms 1 (HSD11B1) and 2 (HSD11B2), have been demonstrated to be the regulators of the local level of active glucocorticoid, which has a broad range of physiological actions. In the present study, the potency of zearalenone was tested for the inhibition of HSD11B1 and HSD11B2 in rat and human tissues. Zearalenone showed potent inhibition of HSD11B2 with the half-maximal inhibitory concentration (IC50) calculated at 49.63 and 32.22 μM for the rat and human, respectively. Results showed that zearalenone competitively inhibited HSD11B2 when a steroid substrate was used. However, it served as an uncompetitive inhibitory factor when the cofactor NAD(+) was used. In contrast, the potency of zearalenone to inhibit both rat and human HSD11B1 was diminished, with the concentration of 100 μM causing almost no inhibitory effect on the isoform. In conclusion, we observed that zearalenone is a selective inhibitor of HSD11B2, implying that this agent may cause excessive glucocorticoid action in local tissues such as kidney and placentas.
authors.affiliation: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Linxi
authors.initials: L
authors.lastname: Li
authors.affiliation: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Hongguo
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Baiping
authors.initials: B
authors.lastname: Mao
authors.affiliation: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Heilongjiang Key Laboratory of Anti-Fibrosis Biotherapy, Mudanjiang Medical University, Heilongjiang 157011, China.
authors.forename: Xiaohuan
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Heilongjiang Key Laboratory of Anti-Fibrosis Biotherapy, Mudanjiang Medical University, Heilongjiang 157011, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Anesthesia, Hangzhou Hospital Affiliated to Nanjing Medical University, Hangzhou First People's Hospital, Hangzhou 310006, China.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009243:NAD / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D015025:Zearalenone / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D009243:NAD; D015025:Zearalenone; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human