Developmental changes of proteoglycan synthesis in rat liver and isolated hepatocytes

The synthesis of sulfated proteoglycans in late fetal (19th to 22nd day of intrauterine life), early postnatal, and adult liver tissue as well as in hepatocytes and their distribution in plasma membranes were studied. Overall proteoglycan production is enhanced two-fold in fetal as compared with adult liver tissue. In contrast to slices from adult liver, in which the synthesis of heparan [35S]-sulfate comprises more than 80% and chondroitin sulfate less than 5% of total glycosaminoglycans, chondroitin [35S]sulfate is the major type of glycosaminoglycans synthesized in fetal liver representing about 50% of total sulfated glycosaminoglycans. Thus, the synthesis of chondroitin sulfate is elevated nearly 30-fold in fetal liver as compared with the adult counterpart. Immediately after birth chondroitin sulfate formation decreases rapidly reaching adult levels between the 10th and 15th day of postnatal life. The production of heparan sulfate is almost unchanged during perinatal liver development due to a relatively low fractional synthesis of heparan [35S]sulfate in fetal liver. Hepatocytes were identified as the cell type responsible for elevated chondroitin sulfate production in fetal liver. Erythroblasts, which synthesize chondroitin sulfate, contribute less than 10% to total glycosaminoglycan synthesis in embryonic liver. Plasma membranes of adult liver contain exclusively heparan sulfate whereas in neonatal liver cell membranes 25% of labeled glycosaminoglycans is represented by chondroitin sulfate, a fraction which decreases rapidly after birth. In parallel to the postnatal shut down of chondroitin sulfate synthesis the activity of the UDPxylose:coreprotein xylosyltransferase (EC. 2.4.2.26) decreases from 4.8 +/- 0.5 dpm/h per microgram protein to 0.3 +/- 0.1 dpm/h per microgram protein suggesting a regulatory function of the enzyme for proteochondroitin sulfate synthesis in developing liver. The formation of both heparan sulfate and chondroitin sulfate is dependent on functioning protein synthesis, which indicates, together with double labeling experiments using [3H]serine and [14C]glucosamine as isotopic precursors, their synthesis as proteoglycans. The positive correlation (r = 0.949) between the incorporation of [3H]thymidine into DNA and chondroitin [35S]sulfate production supports the assumption of a cell growth promoting activity of chondroitin sulfate and points to a significant role of the glycosaminoglycan in the process of cellular proliferation and tissue differentiation.