Biotransformation of 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-1-propynyl-estra-4,9-dien-3-one (RU486) in rat hepatoma variants.
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.
Chasserot-Golaz
S
S
Unité Propre de Recherche No. 9002 du CNRS, Strasbourg, France.
Beck
G
G
Venetianer
A
A
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003907:Dexamethasone / Q000037:antagonists & inhibitors; D004790:Enzyme Induction; D015735:Mifepristone / Q000378:metabolism* / Q000494:pharmacology; D010634:Phenobarbital / Q000037:antagonists & inhibitors; D051381:Rats; D014217:Troleandomycin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D065607:Cytochrome P-450 Enzyme Inhibitors; D015735:Mifepristone; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D014217:Troleandomycin; D010634:Phenobarbital