Altered acinar distribution of glutamine synthetase and different growth response of cultured enzyme-positive and -negative hepatocytes after partial hepatectomy.

Partial hepatectomy (PH) results in the persistent drop of the specific activity of glutamine synthetase (GS) (EC 6.3.1.2). This drop correlates with the reduced proportion of GS+ hepatocytes and with the reduced GS+ area surrounding the central veins such that GS+ hepatocytes are arranged in a single cell layer only. Cultivation of hepatocytes isolated at various times after PH revealed considerable differences in the growth characteristics of GS+ and GS- hepatocytes discriminated by immunocytochemistry. In the absence or presence of epidermal growth factor and insulin, the labeling index of GS- hepatocytes peaked in cultures established 48 h after PH at 10% and 50%, respectively, while that of GS+ cells was much lower (2% and 6%). In cultures established at later times after PH the labeling index of GS- cells decreased gradually, while that of GS+ hepatocytes increased continuously, reaching about 20% and more than 50% for controls and epidermal growth factor/insulin-treated cultures, respectively, in cultures established 72 after PH. Norepinephrine stimulated the labeling index of both cell populations during the first 24 h only, but again GS- hepatocytes responded somewhat earlier than did GS+ hepatocytes. These results demonstrate that the differences in the growth characteristics of GS+ and GS- hepatocytes are due to different priming of these cells in vivo and may result in the different expansion of the respective cell populations during regeneration after PH.