Chasserot-Golaz S, Beck G, Venetianer A
Unité Propre de Recherche No. 9002 du CNRS, Strasbourg, France.
Biochem Pharmacol. 1993 Dec 3;46(11):2100-3. doi: 10.1016/0006-2952(93)90654-f.
Metabolism of the synthetic steroid 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-1-propynyl-estra-4,9-dien-3-one (RU486) occurs in the dedifferentiated S-H56-125 variant of Reuber hepatoma. Considering that rat liver cytochrome P450 (P450) monooxygenases are engaged in different oxidative steps of the metabolism of RU486, the influence of several prototype P450 inducers was investigated. The data obtained by treating H56 and S-H56-125 hepatoma cells with different P450 inducers (dexamethasone (DEX), benzanthracene, phenobarbital) or with a specific P450 inhibitor, troleandomycin, led us to conclude that CYP3A is involved in the hydroxylation of RU486. This form is induced by DEX independently of the availability of the canonical glucocorticoid receptor.
合成甾体17β-羟基-11β-（4-二甲基氨基苯基）-17α-1-丙炔基-雌甾-4,9-二烯-3-酮（RU486）的代谢发生在去分化的鲁伯肝癌S-H56-125变体中。鉴于大鼠肝细胞色素P450（P450）单加氧酶参与RU486代谢的不同氧化步骤，研究了几种原型P450诱导剂的影响。用不同的P450诱导剂（地塞米松（DEX）、苯并蒽、苯巴比妥）或特异性P450抑制剂三乙酰竹桃霉素处理H56和S-H56-125肝癌细胞所获得的数据，使我们得出结论：CYP3A参与RU486的羟基化反应。这种形式可由DEX诱导，且与经典糖皮质激素受体的可用性无关。
