DEVELOPMENTAL-CHANGES IN THE CONSTITUTIVE AND INDUCIBLE EXPRESSION OFCYTOCHROME-P450 3A2

Using a CYP3A2-specific oligonucleotide and an antipeptide antibody ra ised against the C terminus of CYP3A2 (VINGA) it is demonstrated that metyrapone administration to adult (12 weeks old) but not immature (3 weeks old) male Sprague Dawley rats induces the hepatic expression of CYP3A2 mRNA and protein. The constitutively expressed level of CYP3A2 protein in adult male rats is markedly lower than the levels expressed in immature rats as determined using the anti-VINGA antibody, in cont rast to previous reports using antibodies that do not discriminate bet ween CYP3A forms. Hepatic microsomal CYP3A2 protein expression, examin ed between 3 and 15 weeks of age, is extinguished between 9 and 12 wee ks of age in contrast to immunoreactive CYP3A protein (determined usin g a nonselective antibody) and CYP3A-dependent androstenedione 6 beta- hydroxylase activity. These data suggest that the regulation of the in duction of CYP3A2 is developmentally controlled and that the major exp ressed adult form(s) of constitutively expressed CYP3A is not CYP3A2. (C) 1997 Elsevier Science Inc.