Different proliferative activity in vitro of periportal and perivenous hepatocytes

The different growth potentials of hepatocytes from different zones of the liver acinus were assessed in vitro by autoradiography with immunocytochemical discrimination of periportal and perivenous hepatocytes by the marker enzyme glutamine synthetase (GS) or their direct isolation by the digitonin/collagenase perfusion technique. All stimuli studied led to much higher labeling indices in GS-negative than in GS-positive cells in cultures both of all hepatocytes and of the perivenous subfraction. In contrast, the response of GS-negative hepatocytes in the periportal and in the perivenous subfractions differed only gradually depending of the growth stimulus. It is concluded that GS-positive hepatocytes are distinguished from all other hepatocytes by a completely different growth characteristics, which may play a dominant role in the regenerative remodelling of zone 3. The wave-like spatiotemporal pattern of DNA synthesis during liver regeneration, however, seems to be due to gradual changes in growth responsiveness of the hepatocytes along the acinus.