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...