The effect of synthetic glucocorticoid, dexamethasone on CYP1A1 inducibility in adult rat and human hepatocytes.
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.
Monostory
Katalin
K
Chemical Research Center, Hungarian Academy of Sciences, PO Box 17, H-1525 Budapest, Hungary. monostor@chemres.hu
Kohalmy
Krisztina
K
Prough
Russell A
RA
Kóbori
László
L
Vereczkey
László
L
D015660:7-Alkoxycoumarin O-Dealkylase / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D004357:Drug Synergism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation
D005938:Glucocorticoids; D012333:RNA, Messenger; D008748:Methylcholanthrene; D003907:Dexamethasone; D015660:7-Alkoxycoumarin O-Dealkylase; D019363:Cytochrome P-450 CYP1A1