Influence of Cortisol on Glycogen Synthesis and Gluconeogenesis in Fetal Rat Liver in Organ Culture

Cortisol stimulated the synthesis of glycogen in fetal rat liver explants. The increase was proportional to the amount of glucose present in the incubation medium and occurred slowly over a 44-hour period. The ability of cortisol to stimulate glycogen synthesis was accelerated after prior incubation of explants for 42 hours with no steroid. Glucose alone led to the synthesis of very little glycogen. [U-14C]-glucose added to the incubation medium was incorporated into glycogen. The specific activities of [U-14C]glucose in the medium and in glycogen synthesized over a 44-hour period were approximately the same whether or not cortisol was present, indicating that glycogen was derived mainly from glucose. Fetal livers synthesized glucose and glycogen from l-[U-14C]alanine to a limited degree. The incorporation of label ranged from 0.2% to 1.6% of the dose; the extent was determined by the conditions of incubation. Cortisol did not affect the over-all gluconeogenic process, but it increased the proportion of label incorporated into glycogen and decreased the incorporation into glucose. Gluconeogenesis from l-[U-14C]alanine did not take place in the absence of glucose. Cortisol did not induce any changes which could be correlated with glycogen synthesis in the activities of phosphoenolpyruvate carboxykinase, glycogen phosphorylase, glucose 6-phosphatase, fructose 1,6-diphosphatase, pyruvate kinase, alanine aminotransferase, or aspartate aminotransferase. Accumulation of glycogen under all conditions studied was directly proportional to changes in glycogen synthetase b. The a form of the enzyme was not affected by cortisol. It is concluded that (a) the major source of glycogen in fetal rat liver is glucose; (b) synthesis of glycogen from glucose is stimulated by cortisol; (c) gluconeogenesis takes place in fetal liver to a measureable extent; (d) cortisol does not influence gluconeogenesis; (e) cortisol directs a common six-carbon intermediate towards glycogen synthesis and away from glucose formation; (f) the effect of cortisol on glycogen synthesis depends on its ability to increase glycogen synthetase b activity.