Pineau T, Daujat M, Pichard L, Girard F, Angevain J, Bonfils C, Maurel P
Institut National de la Santé et de la Recherche Médicale Unité 128, Centre National de la Recherche Scientifique, Montpellier, France.
Eur J Biochem. 1991 Apr 10;197(1):145-53. doi: 10.1111/j.1432-1033.1991.tb15893.x.
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.
对家兔中CYP1A1、CYP1A2和CYP3A6的发育表达进行了研究。细胞色素P450IA1、P450IA2和P450IIIA6呈现出相似的发育表达模式。在新生动物直至第3周时，这些蛋白质的含量较低（低于0.05 nmol/mg），在第3周和第4周之间急剧积累，到第4周达到最高值（P450IA1，0.2 nmol/mg；P450IA2，0.8 nmol/mg；P450IIIA6，0.12 nmol/mg），而在成年动物中则下降（P450IA1，0.2 nmol/mg；P450IA2，0.4 nmol/mg；P450IIIA6，0.09 nmol/mg）。细胞色素P450IA1和P450IA2在未处理的胎儿中不表达。CYP3A6基因表达在妊娠第30天开始，仅在出生前不久，即妊娠第28天至30天对雌性动物进行处理后，转录和mRNA积累可通过利福平经胎盘诱导。长（1.85 kb）和短（1.7 kb）的mRNA转录本在未处理或经利福平处理的胎儿中均有表达。CYP3A6基因表达在1周龄和2周龄动物中也可被利福平诱导。CYP1A1和CYP1A2基因的发育表达与第3 - 4周断奶时伴随的饮食变化密切相关。在延迟（第6周）或早期（第2周）断奶的动物中，信息、蛋白质和相关活性的急剧积累相对于正常断奶相应延迟或提前。当用商业兔饲料的主要成分生物级苜蓿（在无化肥、农药等条件下种植）重复进行人工定时断奶时，得到了类似的结果。虽然第2周早期断奶可使CYP3A6基因表达提前，但第6周延迟断奶后，信息和蛋白质均未表现出积累增加，仍保持在新生动物的低水平。用三碘甲状腺原氨酸处理1周龄和2周龄动物，或用抗甲状腺因子丙基硫氧嘧啶处理3周龄动物，均未改变CYP1A1、CYP1A2和CYP3A6基因发育表达的正常模式。得出以下结论：（a）胎儿中CYP3A6基因表达在妊娠第30天开始，（b）该基因的表达可被利福平经胎盘诱导，（c）CYP1A1、CYP1A2和CYP3A6基因表达在断奶时急剧激活，（d）甲状腺激素似乎与家兔中这些基因的发育表达模式无关。
