Developmental changes in the constitutive and inducible expression of cytochrome P450 3A2.
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 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 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 6beta-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.
Wright
M C
MC
Department of Toxicology, St Bartholomew's and The Royal London School of Medicine and Dentistry, UK. m.c.wright@mds.qmw.ac.uk
Edwards
R J
RJ
Pimenta
M
M
Ribeiro
V
V
Ratra
G S
GS
Lechner
M C
MC
Paine
A J
AJ
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000235:genetics
D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C022657:steroid hormone 6-beta-hydroxylase; D008797:Metyrapone