GROWTH-HORMONE REGULATION OF HEPATIC GLUTAMINE-SYNTHETASE MESSENGER-RNA LEVELS IN RATS

The expression of glutamine synthetase (GS) in the rat liver is dependent on pituitary growth hormone (GH). RNA blot hybridizations revealed that in hypophysectomized rats the level of glutamine synthetase mRNA was dramatically reduced in liver but not brain. This drop of GS mRNA in the liver results in a reduction of GS enzyme activity as well. Two other messages, phosphoenolpyruvate carboxykinase and glycerol phosphate dehydrogenase were not diminished in the liver, indicating that the effects of hypophysectomy on hepatic GS expression are specific and not part of a general reduction in transcription due to lack of pituitary factors. Daily administration of rat pituitary growth hormone caused an increase in the levels of hepatic GS mRNA as well as enzyme activity. In situ hybridization of normal liver sections with the GS antisense message showed an abundant amount of message confined to the region around each central vein of the hepatic acini, while in the hypophysectomized animal the message for GS is greatly reduced but still only located in hepatocytes surrounding the central vein. Hypophysectomized animals given GH replacement showed a substantial increase in the amount of exposed silver grains only around the central veins. This indicates that GH does not influence the cellular position of GS expression nor the viability of those hepatocytes that express the enzyme, but it does regulate the quantity of GS in the liver through changes in the levels of GS mRNA. © 1990.