Occurrence and inducibility of cytochrome P450IIIA in maternal and fetal rats during prenatal development

Biochemistry. 1989 May 30;28(11):4871-9. doi: 10.1021/bi00437a052.

Abstract

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)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / immunology
  • Cytochrome P-450 Enzyme System / metabolism*
  • Embryonic and Fetal Development*
  • Enzyme Induction / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gestational Age
  • Immunoblotting
  • Male
  • Microsomes, Liver / enzymology*
  • Pregnancy
  • Pregnenolone Carbonitrile / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Substrate Specificity

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Pregnenolone Carbonitrile
  • Cytochrome P-450 Enzyme System