Dexamethasone induction of gamma-glutamyl transferase in primary cultures of hepatocytes is enhanced by metyrapone.
Metyrapone, a cytochrome P-450 inhibitor, reduces by about 3,000 times the dexamethasone concentration required to cause a maximal induction of gamma-glutamyltransferase in adult rat hepatocyte cultures, in itself having no inducing activity. Metyrapone effect decreases as dexamethasone concentration approaches the optimally inducing one. Metyrapone action on low DEX concentrations is dose-dependent while inhibiting 7-ethoxycoumarin O-deethylation by 20% to 75%. At the same doses, metyrapone amplifies also the effects of all the hormonal concentrations inducing tyrosine aminotransferase. These phenomena may be triggered by a modulation of the glucocorticoid biotransformation effective at both transcriptional and translational levels.
Paolicchi
A
A
Dipartimento di Biomedicina Sperimentale, Università di Pisa, Italy.
Chieli
E
E
Tongiani
R
R
D015660:7-Alkoxycoumarin O-Dealkylase / Q000037:antagonists & inhibitors; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000201:enzymology*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis*
D003907:Dexamethasone; D015660:7-Alkoxycoumarin O-Dealkylase; D005723:gamma-Glutamyltransferase; D008797:Metyrapone