Levin M S, Pitt A J, Schwartz A L, Edwards P A, Gordon J I
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Biochim Biophys Acta. 1989 Jun 28;1003(3):293-300. doi: 10.1016/0005-2760(89)90235-x.
Cloned cDNAs encoding a number of enzymes involved in cholesterol biosynthesis as well as extracellular and intracellular lipid transport were used to compare the developmental maturation of these biologic functions in the fetal and neonatal rat and human liver. The results of RNA blot hybridization analyses indicate that steady-state levels of rat HMG-CoA synthase, HMG-CoA reductase and prenyl transferase mRNAs are highest in late fetal life and undergo precipitous (up to 80-fold) co-ordinate reductions immediately after parturition. These changes reflect the ability of the fetal rat liver to produce large quantities of cholesterol as well as the repression of this function during the suckling period in response to exogenous dietary cholesterol. Striking co-ordinate patterns of HMG-CoA synthase, reductase and prenyl-transferase mRNA accumulation were also observed in four extrahepatic rat tissues (brain, lung, intestine and kidney) during the perinatal period. The concentrations of all three mRNAs in the 8-week-old human fetal liver are similar to those observed throughout subsequent intrauterine development with less than 2-fold changes noted between the 8th through 25th weeks of gestation. Analysis of the levels of human apo AI, apo AII, apo B and liver fatty acid binding protein mRNAs during this period and in newborn liver specimens also indicated less than 2-3-fold changes. These observations suggest that the 8-week human liver has achieved a high degree of biochemical differentiation with respect to functions involved in lipid metabolism/transport which may be comparable to that present in 19-21 day fetal rat liver. Further analysis of human and rat fetal liver RNAs using cloned cDNAs should permit construction of a developmental time scale correlating hepatic biochemical differentiation to be constructed between these two mammalian species.
编码多种参与胆固醇生物合成以及细胞外和细胞内脂质转运的酶的克隆cDNA，被用于比较胎鼠和新生鼠以及人类肝脏中这些生物学功能的发育成熟情况。RNA印迹杂交分析结果表明，大鼠HMG-CoA合酶、HMG-CoA还原酶和异戊二烯转移酶mRNA的稳态水平在胎儿后期最高，在分娩后立即经历急剧（高达80倍）的协同降低。这些变化反映了胎鼠肝脏产生大量胆固醇的能力，以及在哺乳期因外源性膳食胆固醇而对该功能的抑制。在围产期，在大鼠的四个肝外组织（脑、肺、肠和肾）中也观察到了HMG-CoA合酶、还原酶和异戊二烯转移酶mRNA积累的显著协同模式。8周龄人类胎儿肝脏中所有三种mRNA的浓度与整个随后的子宫内发育过程中观察到的浓度相似，在妊娠第8周至25周之间变化不到2倍。对这一时期以及新生儿肝脏标本中人类载脂蛋白AI、载脂蛋白AII、载脂蛋白B和肝脏脂肪酸结合蛋白mRNA水平的分析也表明变化不到2至3倍。这些观察结果表明，8周龄的人类肝脏在脂质代谢/转运相关功能方面已经实现了高度的生化分化，这可能与19至21日龄胎鼠肝脏中的情况相当。使用克隆cDNA对人类和胎鼠肝脏RNA进行进一步分析，应该能够构建一个将肝脏生化分化与这两种哺乳动物物种相关联的发育时间尺度。
