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Effects of Hypophysectomy on Amino Acid Metabolism and Gluconeogenesis in the Perfused Rat Liver

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      The effects of hypophysectomy on amino acid metabolism were studied both in vivo and in the perfused rat liver. Hypophysectomized rats exhibited elevated plasma urea concentrations and reduced plasma and liver amino acid levels, while perfused livers from these animals showed enhanced rates of amino acid uptake. No effect of hypophysectomy on hepatic amino acid transport was noted, suggesting that the enhanced hepatic amino acid uptake resulted from an increased flux through the metabolic pathway (or pathways) operating in the liver. Livers from hypophysectomized rats produced substantially more glucose and urea than livers from normal animals when both were perfused with medium containing various levels of amino acids. The rate of glucose synthesis from either labeled alanine, pyruvate, glutamate, or aspartate was stimulated 3- to 4-fold in livers from hypophysectomized rats, showing an increased flux of amino acids through the pathway of gluconeogenesis. Treatment of hypophysectomized rats with growth hormone for 2 days returned the rate of gluconeogenesis from alanine toward normal, although the reversion was incomplete. The data suggested that the enhanced hepatic utilization of amino acids following hypophysectomy resulted from increased metabolism of the compounds in the liver, involving increased fluxes through the pathways of gluconeogenesis and ureogenesis.

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