title: Effects of methoxychlor and its metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane on 11β-hydroxysteroid dehydrogenase activities in vitro.
abstract: Methoxychlor (MXC) is primarily used as a pesticide and widely present in the environment. The objective of the present study is to investigate the direct effects of MXC and its metabolite 2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) on two isoforms of 11β-hydroxysteroid dehydrogenase (11β-HSD1 and 11β-HSD2) in vitro. Human liver microsome, rat testis microsome and adult Leydig cells were used for the measurement of 11β-HSD1 activity. Human placental and rat kidney microsomes were used for 11β-HSD2 activity. The IC(50) values on human 11β-HSD1 by MXC and HPTE were 1.91±0.07 and 8.88 ± 0.08 μM, respectively. HPTE inhibited rat 11β-HSD1 with IC(50) of 9.15±0.05μM, while MXC did not inhibit the enzyme. MXC and HPTE were competitive inhibitors of 11β-HSD1. HPTE also inhibited human and rat 11β-HSD2 with IC(50) values of 55.57 ± 0.08 and 12.96 ± 0.11 μM, respectively, while MXC did not inhibit 11β-HSD2. In summary, our results showed that MXC and its metabolite HPTE inhibited both isoforms of 11β-HSD in a species- and chemical structure-dependent manner.
authors: The 2nd Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325000, PR China.
authors: Jingjing
authors: J
authors: Guo
authors: Haiyun
authors: H
authors: Deng
authors: Hongzhi
authors: H
authors: Li
authors: Qiqi
authors: Q
authors: Zhu
authors: Binghai
authors: B
authors: Zhao
authors: Bingbing
authors: B
authors: Chen
authors: Yanhui
authors: Y
authors: Chu
authors: Ren-Shan
authors: RS
authors: 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; D000328:Adult; D000818:Animals; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008731:Methoxychlor / Q000633:toxicity*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010575:Pesticides / Q000633:toxicity*; D010636:Phenols / Q000633:toxicity*; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D051381:Rats; D013045:Species Specificity
chemical_list: D004791:Enzyme Inhibitors; D010575:Pesticides; D010636:Phenols; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C404910:2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane; D008731:Methoxychlor