Barroso M, Dargouge O, Lechner M C
Laboratório de Bioquímica, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Eur J Biochem. 1988 Mar 1;172(2):363-9. doi: 10.1111/j.1432-1033.1988.tb13895.x.
Cytochrome P450 cDNA clone designated pP450 IGC 1 has been previously isolated from a phenobarbital-induced rat liver cDNA library, characterized and proven to correspond to a constitutive cytochrome P450 sensitive to phenobarbital stimulation. IGC 1 pDNA, as well as a unique synthetic oligonucleotide probe, were used to investigate the mRNA levels at different developmental stages (fetal, male and female rats of various ages) in parallel with the study of the expression of the liver development and male phenotype markers: albumin, alpha-fetoprotein and alpha 2u globulin mRNAs. Cytochrome P450 IGC 1 mRNA responsiveness to phenobarbital administration was studied in animals of both sexes at different developmental stages. P450 IGC 1 mRNA was not detectable in fetuses nor in male or female rat liver before sexual maturation, becoming elevated at 45 days age, increasing up to 3 months and reaching relatively higher levels in the female liver than in the male. The concentrations of P450 IGC 1 mRNA closely paralleled the increases in alpha 2u globulin mRNA in male liver, as analyzed by dot and Northern blot hybridization. However, P450 IGC 1 was markedly induced by phenobarbital already at 20 days age both in males and females while alpha 2u globulin mRNA was not inducible before sexual maturation. It is concluded that the expression of cytochrome P450 IGC 1 mRNA is associated with the sexual maturation being differently modulated in the male and in the female rat liver. This cytochrome P450 isoenzyme may play an important physiological role in sex differential steroid metabolism and susceptibility to cytotoxic and genotoxic agents.
细胞色素P450 cDNA克隆pP450 IGC 1先前已从苯巴比妥诱导的大鼠肝脏cDNA文库中分离出来，经过鉴定并证明它对应于一种对苯巴比妥刺激敏感的组成型细胞色素P450。IGC 1 pDNA以及一种独特的合成寡核苷酸探针，被用于研究不同发育阶段（胎儿、不同年龄的雄性和雌性大鼠）的mRNA水平，同时研究肝脏发育和雄性表型标志物白蛋白、甲胎蛋白和α2u球蛋白mRNA的表达情况。在不同发育阶段的雌雄动物中研究了细胞色素P450 IGC 1 mRNA对苯巴比妥给药的反应性。在胎儿以及性成熟前的雄性或雌性大鼠肝脏中均未检测到P450 IGC 1 mRNA，在45日龄时开始升高，至3个月时持续增加，并且在雌性肝脏中的水平相对高于雄性。通过斑点杂交和Northern杂交分析发现，雄性肝脏中P450 IGC 1 mRNA的浓度与α2u球蛋白mRNA的增加密切平行。然而，在雄性和雌性大鼠中，苯巴比妥在20日龄时就可显著诱导P450 IGC 1，而α2u球蛋白mRNA在性成熟前不可诱导。结论是，细胞色素P450 IGC 1 mRNA的表达与性成熟相关，在雄性和雌性大鼠肝脏中的调节方式不同。这种细胞色素P450同工酶可能在性别差异的类固醇代谢以及对细胞毒性和基因毒性剂的易感性中发挥重要的生理作用。
