The 2nd Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325000, PR China.
Toxicol Lett. 2013 Mar 27;218(1):18-23. doi: 10.1016/j.toxlet.2013.01.002. Epub 2013 Jan 17.
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.
甲氧滴滴涕（MXC）主要用作杀虫剂，广泛存在于环境中。本研究的目的是研究 MXC 及其代谢物 2-双（对-羟苯基）-1,1,1-三氯乙烷（HPTE）对两种 11β-羟甾脱氢酶（11β-HSD1 和 11β-HSD2）同工型的体外直接影响。人肝微粒体、大鼠睾丸微粒体和成年莱迪希细胞用于测量 11β-HSD1 活性。人胎盘和大鼠肾微粒体用于测量 11β-HSD2 活性。MXC 和 HPTE 对人 11β-HSD1 的 IC50 值分别为 1.91±0.07 和 8.88 ± 0.08 μM。HPTE 抑制大鼠 11β-HSD1 的 IC50 值为 9.15±0.05μM，而 MXC 不抑制该酶。MXC 和 HPTE 是 11β-HSD1 的竞争性抑制剂。HPTE 还抑制人源和大鼠源 11β-HSD2，IC50 值分别为 55.57 ± 0.08 和 12.96 ± 0.11 μM，而 MXC 不抑制 11β-HSD2。综上所述，我们的研究结果表明，MXC 和其代谢物 HPTE 以种属和化学结构依赖性的方式抑制两种 11β-HSD 同工型。
