Effects of methoxychlor and its metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane on 11β-hydroxysteroid dehydrogenase activities in vitro

被引：16

作者：

Guo, Jingjing ^{[1
]}

Deng, Haiyun ^{[1
]}

Li, Hongzhi ^{[2
]}

Zhu, Qiqi ^{[1
]}

Zhao, Binghai ^{[2
]}

Chen, Bingbing ^{[3
]}

Chu, Yanhui ^{[2
]}

Ge, Ren-Shan ^{[1
]}

机构：

[1] Wenzhou Med Coll, Affiliated Hosp 2, Wenzhou 325000, Zhejiang, Peoples R China

[2] Mudanjiang Med Univ, Heilongjiang Key Lab Antifibrosis Biotherapy, Mudanjiang, Heilongjiang, Peoples R China

[3] Wenzhou Med Coll, Sch Pharm, Dept Pharmacol, Wenzhou 325000, Zhejiang, Peoples R China

来源：

TOXICOLOGY LETTERS | 2013年 / 218卷 / 01期

关键词：

Methoxychlor; HPTE; Enzyme inhibition; 11 beta-hydroxysteroid dehydrogenase; Glucocorticoid metabolism; RAT LEYDIG-CELLS; BETA-HYDROXYSTEROID DEHYDROGENASE; APPARENT MINERALOCORTICOID EXCESS; VISIBLE BURROW SYSTEM; CORTICOSTEROID; 11-BETA-DEHYDROGENASE; TESTOSTERONE SYNTHESIS; CLONING; ENZYME; MOUSE; RECEPTOR;

D O I：

10.1016/j.toxlet.2013.01.002

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

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 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD1 and 11 beta-HSD2) in vitro. Human liver microsome, rat testis microsome and adult Leydig cells were used for the measurement of 11 beta-HSD1 activity. Human placental and rat kidney microsomes were used for 11 beta-HSD2 activity. The IC50 values on human 11 beta-HSD1 by MXC and HPTE were 1.91 +/- 0.07 and 8.88 +/- 0.08 mu M, respectively. HPTE inhibited rat 11 beta-HSD1 with IC50 of 9.15 +/- 0.05 mu M, while MXC did not inhibit the enzyme. MXC and HPTE were competitive inhibitors of 11 beta-HSD1. HPTE also inhibited human and rat 11 beta-HSD2 with IC50 values of 55.57 +/- 0.08 and 12.96 +/- 0.11 mu M, respectively, while MXC did not inhibit 11 beta-HSD2. In summary, our results showed that MXC and its metabolite HPTE inhibited both isoforms of 11 beta-HSD in a species-and chemical structure-dependent manner. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

引用

页码：18 / 23

页数：6

共 50 条

[21] A metabolite of methoxychlor, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane, reduces testosterone biosynthesis in rat leydig cells through suppression of steady-state messenger ribonucleic acid levels of the cholesterol side-chain cleavage enzyme
Akingbemi, BT
Ge, RS
Klinefelter, GR
Gunsalus, GL
Hardy, MP
BIOLOGY OF REPRODUCTION, 2000, 62 (03) : 571 - 578
[22] ISOLATION OF TETRAKIS(P-METHOXYPHENYL) ETHYLENE FROM COMMERCIAL METHOXYCHLOR[2,2-BIS(4-METHOXYPHENYL)-1,1,1-TRICHLOROETHANE], DMDT
MAZUCH, L
MITCHELL, RH
WEST, PR
CHEMISTRY & INDUSTRY, 1975, (09) : 399 - 400
[23] Studies on thermal Stability of Epoxide Resins Obtained from 2-Bis(P-Hydroxyphenyl)-1,1,1-Trichloroethane.
Brzozowski, Zbigniew K.
Brzozowska-Janiak, Teresa
Porejko, Stanislaw
Florianczyk, Tadeusz
Polimery, 1972, 17 (08): : 419 - 422
[24] The percutaneous absorption of DDT (2,2-bis (p-chlorophenyl) 1,1,1-trichloroethane) in laboratory animals
Draize, JH
Nelson, AA
Calvery, HO
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 1944, 82 (02): : 159 - 166
[25] CRYSTAL STRUCTURE OF DDT [2,2-BIS(PARA-CHLOROPHENYL) 1,1,1-TRICHLOROETHANE]
CLARK, GL
CAGLE, FW
SCIENCE, 1945, 101 (2627) : 465 - 466
[26] FATE OF P,P'-DDT [2,2-BIS(P-CHLOROPHENYL)-1,1,1-TRICHLOROETHANE] IN DOGFISH, SQUALUS-ACANTHIAS
DVORCHIK, BH
MAREN, TH
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY, 1972, 42 (1A): : 205 - &
[27] QUANTITATIVE NMR DETERMINATION OF JOINTLY PRESENT 2,2-BIS(4-HYDROXYPHENYL)-1,1,1-TRICHLOROETHANE, 2,2-BIS(4-HYDROXYPHENYL)-1,1-DICHLOROETHYLENE, AND EPOXY-RESINS ON THEIR BASIS
KARPOV, ON
JOURNAL OF ANALYTICAL CHEMISTRY, 1995, 50 (02) : 205 - 207
[28] EFFECTS OF 2,2-BIS(PARA "CHLOROPHENYL)-1,1,1-TRICHLOROETHANE (DDT) ON SODIUM-TRANSPORT IN TOAD BLADDER
SIDES, PJ
FINN, AL
AMERICAN JOURNAL OF PATHOLOGY, 1973, 70 (02): : A58 - A59
[29] COMPARATIVE CHRONIC TOXICITY FOR WARM-BLOODED ANIMALS OF 2,2-BIS-(PARA-CHLOROPHENYL)-1,1,1-TRICHLOROETHANE (DDT) AND 2,2-BIS-(PARA-METHOXYPHENYL)-1,1,1-TRICHLOROETHANE (DMDT,METHOXYCHLOR)
HAAG, HB
FINNEGAN, JK
LARSON, PS
RIESE, W
DREYFUSS, ML
ARCHIVES INTERNATIONALES DE PHARMACODYNAMIE ET DE THERAPIE, 1950, 83 (04): : 491 - 504
[30] THE CHRONIC ORAL TOXICITY OF DDT (2,2-BIS(PARA-CHLOROPHENYL-1,1,1-TRICHLOROETHANE)
FITZHUGH, OG
NELSON, AA
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 1947, 89 (01): : 18 - 30

← 1 2 3 4 5 →