Expression of the oncofetal protein in the fetal development of the liver.

γ -谷氨酰转肽酶（γ - gt）是一种膜结合酶，它催化氨基酸和肽的γ -谷氨酰基部分水解，并将g-谷氨酰基残基转移到其他氨基酸和肽中。它被认为是一种癌胎蛋白，据报道，它参与肝脏氨基酸和多肽的细胞膜转运、肾脏氨生成和亮氨酸的产生。本研究的目的是测量胎儿发育过程中人类肝脏中γ - gt mRNA的含量，并确定γ - gt蛋白的含量和定位，以了解γ - gt在肝脏发育中的可能作用。采用Nonhem分析和γ - gt cDNA原位杂交技术检测胎儿发育过程中肝脏γ - gt基因的表达。早在妊娠12周就可以检测到这种表达，然后在妊娠40周即出生前逐渐增加到峰值。胎儿肝脏的最高表达水平是成人肝脏的10倍，与肝细胞癌相当。使用抗人γ - gt单克隆抗体免疫组织化学方法测定肝脏γ - gt的产生和定位。在mRNA合成增加的同时，观察到免疫染色的面积和强度增加。此外，γ - gr蛋白在低表达时限制性地局限于胆管壁上，而在高表达时则广泛分布于胎儿肝细胞的细胞膜上。

Gamma-glutamyl transpeptidase (gamma-GT) is a membrane-bound enzyme which catalyzes hydrolysis of the gamma glutamyl moiety of amino acids and peptides, and transfers the g-glutamyl residue to the other amino acids and peptides. It is considered to be an oncofetal protein and has been reported to be involved in detoxification in cell membrane transport of amino acids and peptides in liver, ammoniagenesis in kidney, and production of leucotfienes. The aim of the present study was to measure the amount of gamma-GT mRNA and to determine the amount and localization of gamma-GT protein in human liver during fetal development to understand the possible role of gamma-GT in liver development.Expression of human gamma-GT gene in liver during fetal development was examined using Nonhem analysis and in situ hybridization by gamma-GT cDNA as a probe. The expression was detectable as early as at week 12 of gestation and then increased gradually to a peak at week 40, just before birth. The maximal level of the expression in the fetal liver was ten-fold higher than that in adult liver and comparable to that in a hepatocellular carcinoma.Production and localization of gamma-GT in liver were determined immunohistochemically using monoclonal antibodies against human gamma-GT. In parallel to the increase in mRNA synthesis, an increase in areas as well as intensity of immunostaining was observed. Furthermore, gamma-Gr protein was shown to be localized restrictively oil the wall of bile canaliculi when the expression was low, but distributed widely over all along the cell membrane of the fetal liepatocytes when the expression was high.