BIOTRANSFORMATION OF 17-BETA-HYDROXY-LL-BETA-(4-DIMETHYLAMINOPHENYL)17-ALPHA-1-PROPYNYL-ESTRA-4,9-DIEN-3-ONE (RU486) IN RAT HEPATOMA VARIANTS

被引：8

作者：

CHASSEROTGOLAZ, S

BECK, G

VENETIANER, A

机构：

[1] CNRS,UNITE PROPRE RECH 9002,F-67000 STRASBOURG,FRANCE

[2] INST GENET,BIOL RES CTR,H-6701 SZEGED,HUNGARY

来源：

BIOCHEMICAL PHARMACOLOGY | 1993年 / 46卷 / 11期

基金：

匈牙利科学研究基金会;

关键词：

D O I：

10.1016/0006-2952(93)90654-F

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：2100 / 2103

页数：4

共 23 条

[1] PARADOXICAL TRANSCRIPTIONAL ACTIVATION OF RAT-LIVER CYTOCHROME-P-450 3A1 BY DEXAMETHASONE AND THE ANTIGLUCOCORTICOID PREGNENOLONE 16-ALPHA-CARBONITRILE - ANALYSIS BY TRANSIENT TRANSFECTION INTO PRIMARY MONOLAYER-CULTURES OF ADULT-RAT HEPATOCYTES [J].