The effect of synthetic glucocorticoid, dexamethasone on CYP1A1 inducibility in adult rat and human hepatocytes

FEBS Lett. 2005 Jan 3;579(1):229-35. doi: 10.1016/j.febslet.2004.11.080.

Abstract

Glucocorticoids act synergistically with polycyclic aromatic hydrocarbons in increasing mRNA and protein levels of CYP1A1 in rat liver. The action of dexamethasone to modify CYP1A1 expression has been investigated in adult human hepatocytes. The effect of dexamethasone on the induction of CYP1A1 by 3-methylcholanthrene is different in rat and human liver cells. Dexamethasone potentiates the induction of CYP1A1 about 3- to 4-fold in rat cells. In human hepatocytes, it reduces CYP1A1 induction by 50-60% at enzyme protein level, while it does not have an effect on CYP1A1 mRNA amount.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 7-Alkoxycoumarin O-Dealkylase / biosynthesis
  • Adolescent
  • Adult
  • Aged
  • Animals
  • Cytochrome P-450 CYP1A1 / analysis
  • Cytochrome P-450 CYP1A1 / biosynthesis*
  • Cytochrome P-450 CYP1A1 / genetics
  • Dexamethasone / pharmacology*
  • Down-Regulation
  • Drug Synergism
  • Female
  • Gene Expression / drug effects
  • Glucocorticoids / pharmacology*
  • Hepatocytes / drug effects
  • Hepatocytes / enzymology*
  • Humans
  • Male
  • Methylcholanthrene / pharmacology
  • Middle Aged
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Rats
  • Up-Regulation

Substances

  • Glucocorticoids
  • RNA, Messenger
  • Methylcholanthrene
  • Dexamethasone
  • 7-Alkoxycoumarin O-Dealkylase
  • Cytochrome P-450 CYP1A1