Wagenaar G T, Geerts W J, Chamuleau R A, Deutz N E, Lamers W H
Department of Anatomy and Embryology, Academic Medical Centre, University of Amsterdam, The Netherlands.
Biochim Biophys Acta. 1994 Aug 18;1200(3):265-70. doi: 10.1016/0304-4165(94)90166-x.
Carbamoylphosphate synthase and glutamine synthase show a complementary distribution in the liver lobule of the rat. In the human liver lobule, which is approximately 2-fold larger than that of the rat, an intermediate, 'empty' zone is present between the periportal carbamoylphosphate synthase-positive and the pericentral glutamine synthase-positive zone. To investigate whether these differences in gene expression can be attributed to the size of the liver lobule, we investigated the patterns of expression of carbamoylphosphate synthase, glutamine synthase and glutamate dehydrogenase during postnatal development of the pig, a species in which the total number of lobules does not increase after birth. We demonstrate that lobular size increases 3-fold between 1 week and 8 months after birth. In the same developmental period the number of hepatocytes on the porto-central axis increases 2-fold, resulting in a 3-fold increase in cellular volume. However, the lobular patterns of expression of carbamoylphosphate synthase, glutamate dehydrogenase and glutamine synthase do not change anymore after 1 month, i.e., when lobular diameter is comparable to that in rat liver, showing that lobular size is not a major determinant of the heterogeneous patterns of expression of these enzymes. The adult patterns of expression of glutamine synthase, glutamate dehydrogenase and, in particular carbamoylphosphate synthase in the porcine liver resemble those of man. Changes in the enzyme activities of glutamate dehydrogenase and carbamoylphosphate synthase are not related to the lobular size. However, the 70% decrease of GS activity in the 8-month-old pigs corresponds with the gradual 2-3-fold decrease in the size of the GS-positive compartment during postnatal development. During adulthood GS activity increases again to values observed 1 week after birth demonstrating a 2-fold increase in cellular glutamine synthase content. The present data show that the pig is an excellent model to study the regulation and functional implication of zonation of gene expression in the human liver.
氨甲酰磷酸合成酶和谷氨酰胺合成酶在大鼠肝小叶中呈互补分布。在人类肝小叶中，其大小约为大鼠肝小叶的2倍，在门静脉周围氨甲酰磷酸合成酶阳性区和中央静脉周围谷氨酰胺合成酶阳性区之间存在一个中间的“空白”区。为了研究这些基因表达差异是否可归因于肝小叶大小，我们研究了猪出生后发育过程中氨甲酰磷酸合成酶、谷氨酰胺合成酶和谷氨酸脱氢酶的表达模式，猪是一种出生后肝小叶总数不增加的物种。我们证明，出生后1周和8个月之间肝小叶大小增加了3倍。在同一发育时期，门静脉-中央静脉轴上的肝细胞数量增加了2倍，导致细胞体积增加了3倍。然而，氨甲酰磷酸合成酶、谷氨酸脱氢酶和谷氨酰胺合成酶的小叶表达模式在1个月后不再改变，即当小叶直径与大鼠肝脏相当时，表明小叶大小不是这些酶表达异质性模式的主要决定因素。猪肝脏中谷氨酰胺合成酶、谷氨酸脱氢酶，特别是氨甲酰磷酸合成酶的成年表达模式与人相似。谷氨酸脱氢酶和氨甲酰磷酸合成酶的酶活性变化与小叶大小无关。然而，8月龄猪中GS活性降低70%与出生后发育过程中GS阳性区大小逐渐降低2 - 3倍相对应。成年期GS活性再次增加到出生后1周时观察到的值，表明细胞谷氨酰胺合成酶含量增加了2倍。目前的数据表明，猪是研究人类肝脏基因表达区域化调控及其功能意义的优秀模型。
