SELECTIVE EXPRESSION OF CYTOCHROME-P450 CYP3A MESSENGER-RNAS IN EMBRYONIC AND ADULT HUMAN LIVER

The human CYP3A P450 family, composed of at least four highly homologo us genes, is expressed prominently in the liver. To investigate the ex pression of CYP3A family members individually, we prepared oligonucleo tides specific for each CYP3A mRNA and used Northern blot analysis and /or polymerase chain reaction to examine RNA from adult and fetal live r for variation in expression of the CYP3A forms during development. W e found that CYP3A4 (P450NF) mRNA, was only detectable by Northern blo t postnatally, was highly variable (10-fold) among the adult samples, and, unlike its rat counterparts (CYP3A1/2), was not influenced by gen der. In contrast, CYP3A7 (HFLa) mRNA, a form previously thought to be confined to fetal liver, was found in all tested samples of fetal live r as well as in seven of 13 adult livers (54%). CYP3A5 (HLp2), an mRNA also found in atl the fetal samples, was detected in three of these 1 3 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 varia ble (<2.5-fold) than CYP3A4 in adults. We conclude, that contrary to p revailing views, expression of CYP3A7 in the liver is not restricted t o the fetus but rather represents a second CYP3A form selectively expr essed in adults.