Occurrence and inducibility of cytochrome P450IIIA in maternal and fetal rats during prenatal development.
The purpose of this study was to quantify cytochrome P450IIIA1 in fetal and maternal livers of uninduced and pregnenolone-16 alpha-carbonitrile (PCN) induced rats during the course of prenatal development. The activities and levels of P450IIIA in hepatic microsomes from maternal rats and fetuses at 15-21 days of gestation were measured by triacetyloleandomycin (TAO) inhibited debenzylation of (benzyloxy)phenoxazone and by immunoassay with defined antiserum specific for P450IIIA. P450IIIA was not detectable (less than 10 pmol/mg for maternal microsomes and less than 2 pmol/mg for fetal microsomes) by immunoassay in uninduced maternal or fetal livers. In hepatic microsomes from PCN-induced dams, values ranged from 59.3 to 116 micrograms P450IIIA1/mg of protein during the same gestational period. Changes in debenzylase activity of 15.9-46.5 pmol of resorufin (mg of protein)-1 min-1 were consistent with these findings as were the changes in TAO-inhibitable debenzylase activity. In the transplancentally induced fetal liver, debenzylase activity increased steadily from 0.19 pmol of resorufin mg-1 min-1 at day 15 to 9.34 pmol of resorufin mg-1 min-1 at day 21 and was paralleled by the TAO-inhibitable activity that ranged from 0.09 pmol of resorufin mg-1 min-1 at day 15 to 3.33 pmol of resorufin mg-1 min-1 at day 21. The amount of immunoreactive P450IIIA1 also increased from 0.5 to 28.7 micrograms/mg of microsomal protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
J E
JE
Hulla
M R
MR
Juchau
D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D004790:Enzyme Induction / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005865:Gestational Age; D015151:Immunoblotting; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D011247:Pregnancy; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D065607:Cytochrome P-450 Enzyme Inhibitors; D011285:Pregnenolone Carbonitrile; D003577:Cytochrome P-450 Enzyme System