Localization of glycogen phosphorylase activity in liver of fasted normal and adrenalectomized rats and in fasted adrenalectomized rats after injection of dexamethasone.

Abstract

The intralobular distribution of activity of glycogen phosphorylase (GP), a key enzyme in the breakdown of glycogen, was evaluated to determine changes during early glycogen synthesis. Hepatic GP activity was localized in normal and adrenalectomized (ADX) rats after fasting overnight and in fasted ADX rats stimulated to synthesize glycogen by administration of dexamethasone (DEX) 2-8 h prior to sacrifice. Cryostat sections were incubated in medium containing appropriate substrate for demonstration of GP activity as indicated by glycogen synthesized by the enzyme during incubation. In sections from fasted normal rats, GP activity in hepatocytes varied from undetectable to substantial amounts with no notable periportal to pericentral gradient evident. In contrast, GP activity in sections from adrenalectomized fasted rats was concentrated in discrete aggregates in random hepatocytes throughout lobules. Two hours after DEX injection, GP enzyme activity occurred as single aggregates or in a dispersed pattern in many hepatocytes. By 4 h after DEX administration, most cells displayed GP enzyme activity, the concentration of which appeared to be greater in pericentral cells than in periportal cells. Eight hours after injection of DEX, GP enzyme activity had increased and appeared more evenly distributed throughout the lobules. These results suggest that GP activity became concentrated in limited regions of selected hepatocytes in fasted ADX rats. DEX stimulation of glycogen synthesis in these rats resulted in increased GP activity that was concentrated in pericentral cells after 4 h. After 8 h, activity increased and was more evenly distributed throughout the lobules. The increase in GP enzyme activity concurrent with overall glycogen synthesis suggests that the enzyme may participate in glycogen turnover.