Selective expression of cytochrome P450 CYP3A mRNAs in embryonic and adult human liver.
The human CYP3A P450 family, composed of at least four highly homologous genes, is expressed prominently in the liver. To investigate the expression of CYP3A family members individually, we prepared oligonucleotides specific for each CYP3A mRNA and used Northern blot analysis and/or polymerase chain reaction to examine RNA from adult and fetal liver for variation in expression of the CYP3A forms during development. We found that CYP3A4 (P450NF) mRNA, was only detectable by Northern blot postnatally, was highly variable (10-fold) among the adult samples, and, unlike its rat counterparts (CYP3A1/2), was not influenced by gender. In contrast, CYP3A7 (HFLa) mRNA, a form previously thought to be confined to fetal liver, was found in all tested samples of fetal liver as well as in seven of 13 adult livers (54%). CYP3A5 (HLp2), an mRNA also found in all the fetal samples, was detected in three of these 13 adults (23%) and two of these three co-expressed CYP3A7 mRNA. CYP3A5 and CYP3A7 are expressed at similar levels in fetal liver from either gender. Moreover, CYP3A7 expression in fetal liver appears less variable (< 2.5-fold) than CYP3A4 in adults. We conclude, that contrary to prevailing views, expression of CYP3A7 in the liver is not restricted to the fetus but rather represents a second CYP3A form selectively expressed in adults.
Schuetz
J D
JD
Department of Medicine, Medical College of Virginia, Richmond 23298-0267.
Beach
D L
DL
Guzelian
P S
PS
D000328:Adult; D001483:Base Sequence; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008099:Liver / Q000196:embryology* / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis*
D017931:DNA Primers; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1