DIFFERENTIAL EXPRESSION PATTERN OF S-ADENOSYLMETHIONINE SYNTHETASE ISOENZYMES DURING RAT-LIVER DEVELOPMENT

The pattern of expression of Liver-specific and extrahepatic S-adenosy lmethionine (SAM) synthetase in developing rat liver was established b y determining steady-state levels of the respective messenger RNAs (mR NAs) and protein content. Levels of Liver-specific SAM synthetase mRNA increased progressively from day 20 of gestation, increased 10-fold i mmediately after birth, and reached a peak at 10 days of age, decreasi ng slightly by adulthood. Conversely, mRNA levels of extrahepatic isoe nzyme decreased toward birth, increased threefold in the newborn, and decreased further in the postnatal life, reaching a minimum in the adu lt. Similar expression profiles were observed in isolated hepatocytes, indicating that both mRNAs are differentially regulated in the same c ell type. Western blot analysis showed that levels of immunoreactive l iver-specific isoenzyme followed a trend similar to the mRNA, indicati ng that developmental regulation of this enzyme is mediated at the mRN A level. Developmental patterns of expression of albumin and alpha-fet oprotein (AFP) mRNAs were closely related to those for liver-specific and extrahepatic isoenzymes, respectively. Therefore, it is suggested that liver-specific SAM synthetase may be a marker for hepatocyte diff erentiation. Incubation of primary cultures of hepatocytes from 21-day -old fetuses with permeant cyclic adenosine monophosphate (cAMP) analo gues elicited an up-regulation of the mRNA for the liver-specific isoe nzyme with a concomitant down-regulation of the extrahepatic message, suggesting a physiological role for the increased postnatal glucagonem ia in the control of this isoenzyme switching. In contrast with the is oenzyme expression profiles, the levels of SAM, the product of SAM syn thetase reaction, were determined to be greater during gestation than in immediate postnatal periods. These results indicate that synthesis and utilization of SAM may be regulated differentially in fetal and ad ult hepatocytes.