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，其催化氨基酸和肽的γ-谷氨酰部分的水解，并将g-谷氨酰残基转移到其他氨基酸和肽。它被认为是一种癌胚蛋白，据报道参与肝脏中氨基酸和肽的细胞膜转运中的解毒、肾脏中的氨生成以及白细胞生成素的产生。为探讨γ-GT在胎儿肝脏发育过程中的作用，本研究以γ-GT cDNA为探针，采用原位杂交和Nonhem分析技术，检测了胎儿肝脏中γ-GT基因的表达。早在妊娠12周就可检测到表达，然后逐渐增加，在出生前40周达到峰值。用抗人γ-GT的单克隆抗体免疫组化法测定了γ-GT在胎儿肝脏中的表达，结果表明，γ-GT在胎儿肝脏中的表达水平是成人肝脏的10倍，与肝细胞癌的表达水平相当。γ-Gr蛋白低表达时局限于胆小管壁，高表达时广泛分布于胎肝细胞膜的整个沿着壁。

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.