Elsevier

Biochemical Pharmacology

Volume 54, Issue 7, 1 October 1997, Pages 841-846
Biochemical Pharmacology

Short communication
Developmental changes in the constitutive and inducible expression of cytochrome p450 3a2

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Abstract

Using a CYP3A2-specific oligonucleotide and an antipeptide antibody raised 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 consdtutively 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 contrast to previous reports using antibodies that do not discriminate between CYP3A forms. Hepatic microsomal CYP3A2 protein expression, examined between 3 and 15 weeks of age, is extinguished between 9 and 12 weeks of age in contrast to immunoreactive CYP3A protein (determined using a nonselective antibody) and CYP3A-dependent androstenedione 6β-hydroxylase activity. These data suggest that the regulation of the induction of CYP3A2 is developmentally controlled and that the major expressed adult form(s) of constitutively expressed CYP3A is not CYP3A2.

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Funded by grants BCC/4252/94 (to M. W.) and BPD 4105/94 (to V. R.) in the frame of PRAXIS XXI from the Junta National de Investigaçâo Cientffica e Tecnclögica, Portugal.

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