γ-Glutamyltranspeptidase in the Rat Liver after Portacaval Shunt

Abstract

Extractweight have been re~orted (I. 15). The metabolism of bile salts and y-Glutamyltranspeptidase (GGTP) activity was studied in livers of rats submitted to an end-to-side portacaval shunt (PCS) and in developing animals. To correlate the evolution of the enzymatic activity measured in vitro, histochemical techniques were used to localize enzyme activity in liver tissue. The GGTP activity in the adult rats was low and amounted to 2.0 =k 0.1 pmol/min/g. During fetal development the enzyme activity rose beginning on the 15th gestational day from 630 A 97 to 1,058 + 20 on the first postnatal day. I'hen the values declined and reached nearly adult values from the 10th postnatal day.After PCS the GGTP activity exhibited a three-to sixfold increase (130 + 69 to 371 + 131) as compared with uneperated adult controls (53 & 13). The highest levels corresponded to those observed between the 3rd and 5th postnatal day in the developing rats. The histochemistry of GGTP in the fetal and newborn liver showed a regular distribution of the enzyme as a fine deposit in the hepatocytes throughout the whole tissue. Ten days after birth the activity was low, at the same level as in the adult rat. In the period after P C S hepatocytes began to show signs of enzymatic activity at the periphery of the hepatic lobules, which subsequently spread through the whole lobules. The increase of GGTP activity after P C S equaled the activity found in fetal animals. That correlated well in both groups with the reappearance of histologically demonstrable enzyme activity in hepatocytes. SpeculationThe consequences of portacaval shunt might be associated with the derepression of an enzyme normally present only in fetal and neonatal rat liver. Since GGTP plays a role in the y-glutamyl cycle, and is responsible, supposedly, for the transport of amino acids into the cell, it may be that in fetal liver and after P C S augmented cellular amino acid transport is an expression of growth and transformation processes.The end-to-side PCS in the rat represents an appropriate model to study experimental hyperammonemia (7, 15) because of the shunting of portal blood to the systemic circulation. In addition to hyperammonemia, portacaval shunting leads to marked changes of the quantity and composition of the blood reaching the liver. The consequences of the shunt operation are therefore multiple. Encephalopathy, testicular atrophy, and changes in body and liver of certain amino ac'ids seeks to'be affected as well (14,(24)(25)(26).These significant morphologic and functional changes are likely to be interpreted as a consequence of shunt-induced alterations in the metabolic stimulation of the liver. Despite considerable work in this field, no common denominator has been found to define the underlying hepatic process of the transformations induced by PCS. To our knowledge the specific hypothesis has not been tested of whether some of the consequences of PCS on hepatic metabolism might be considered as a regression of the liver cell function to a more immature or embr...

Enzymes of Ammonia Detoxication after Portacaval Shunt in the Rat

“…As a direct consequence of portal blood diversion liver shrinkage takes place, the size after 10 days remaining constant (8,10,17). The increased DNA content per unit liver weight in the PCS group and the control group with the same dietary intake compared to unoperated and sham-operated controls show that more cells are present per volume of liver weight.…”

“…A minor fraction of the circulatalone as has been suggested up to now (10), but may also be connected to the reduced food intake of these animals. It is not clear, however, whether the elevated amount of DNA is due to an augmented production of new but smaller and younger hepatocytes, or to shrinkage of the prevailing cells, or both.…”

The Effect of Portal Diversion on the Early Stages of Liver Carcinogenesis in the Rat

“…Weinbren (18) has demonstrated that portacaval shunting in rats can produce nodularity in the liver. Colombo et al (19) have shown that the liver parenchyma becomes positive for GGT after portacaval shunting but the enzymes appear primarily in the periportal zones rather than randomly in small foci of hepatocytes as seen in the model described by Solt et al (1). It seems, therefore, that the GGT positivity seen after shunting is in response to physiological modulation rather than a phenotypic marker for preneoplasia.…”

Portacaval shunt and the reacquisition of γ-glutamyl transpeptidase activity

“…Whether there exists a common denominator to the elevation of hepatic GGT in PCS and in chemically induced hepatocarcinogenesis is not known. The hypothesis that both procedures represent the reacquisition of a fetal, biochemical feature which is normally repressed in the adult is therefore difficult to prove or disprove (8,9). Everts et al believe that after PCS, the distribution of GGT is periportal, whereas after the administration of chemical carcinogens the enzyme is mostly concentrated in the midzonal areas.…”