Developmental expression of rabbit cytochrome P450 CYP1A1, CYP1A2 and CYP3A6 genes. Effect of weaning and rifampicin.
Developmental expression of CYP1A1, CYP1A2 and CYP3A6 in the rabbit have been studied. Cytochromes P450IA1, P450IA2 and P450IIIA6 exhibited comparable patterns of developmental expression. Present at low level (less than 0.05 nmol/mg) in the new born animal up to week 3, these proteins sharply accumulated between weeks 3 and 4 to reach a maximum by week 4 (P450IA1, 0.2 nmol/mg; P450IA2, 0.8 nmol/mg; P450IIIA6, 0.12 nmol/mg) and decreased in the adult (P450IA1, 0.2 nmol/mg; P450IA2, 0.4 nmol/mg; P450IIIA6, 0.09 nmol/mg). Cytochromes P450IA1 and P450IA2 were not expressed in the untreated fetus. Onset of CYP3A6 gene expression occurred at day 30 of gestation and both transcription and mRNA accumulation were transplacentally inducible by rifampicin only shortly before birth, i.e. after treatment of the females between days 28 and 30 of gestation. Both long (1.85 kb) and short (1.7 kb) mRNA transcripts were expressed in untreated or rifampicin-treated fetuses. CYP3A6 gene expression was also induced by rifampicin in 1-week-old and 2-week-old animals. Developmental expression of CYP1A1 and CYP1A2 genes was shown to be closely related to the diet change accompanying weaning which occurs at weeks 3-4. In animals subjected to either delayed (week 6) or early (week 2) weaning, sharp accumulation of messages, proteins and related activities were delayed or anticipated accordingly with respect to normal weaning. Artificially scheduled weaning gave similar results when repeated with biological-grade lucern (grown in the absence of chemical fertilizers, pesticides, etc.), the main constituent of commercial rabbit chow. While CYP3A6 gene expression could be brought forward by early weaning at week 2, both message and protein did not exhibit increased accumulation after delayed weaning at week 6, and remained at the low level of the new born animal. Treatment of 1-week-old and 2-week-old animals with triiodothyronine or of 3-week-old animals with propylthiouracil, an antithyroid factor, did not modify the normal pattern of developmental expression of genes CYP1A1, CYP1A2 and CYP3A6. It is concluded that (a) the onset of CYP3A6 gene expression in the fetus occurs at day 30 of gestation, (b) expression of this gene may be induced transplacentally by rifampicin, (c) CYP1A1, CYP1A2 and CYP3A6 gene expression is sharply activated at weaning, and (d) thyroid hormones appear not to be responsible for the pattern of developmental expression of these genes in the rabbit.
Pineau
T
T
Institut National de la Santé et de la Recherche Médicale Unité 128, Centre National de la Recherche Scientifique, Montpellier, France.
Daujat
M
M
Pichard
L
L
Girard
F
F
Angevain
J
J
Bonfils
C
C
Maurel
P
P
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D004790:Enzyme Induction; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005865:Gestational Age; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000254:growth & development*; D008431:Maternal-Fetal Exchange; D008862:Microsomes, Liver / Q000201:enzymology*; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D012293:Rifampin / Q000494:pharmacology*; D014158:Transcription, Genetic; D014886:Weaning
D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2; D012293:Rifampin