Suppression of glycogen storage with betamethasone 17,21-dipropionate in fetal rat liver—I: Effect on metabolites of the glucogenic pathway and glycogen synthase activity

Abstract

Betamethasone 17,21-dipropionate, a potent synthetic glucocorticoid, showed dose-responsive suppression of glycogen accumulation during late pregnancy in fetal rat liver when it was administered on day 19 of gestation. Complete suppression occurred at a dose of 100 μg/fetus. A similar result was obtained with decapitated fetuses. The change in the levels of metabolites of the glycogenic pathway was examined 5, 10 and 24 hr after injection of 25 or 100 μg of the steroid/fetus. Blockade of glycogen accumulation was observed at 10 hr, as the age-dependent increase in glycogen in control fetuses was detected at that time. UDP-glucose concentration increased at 5 hr and reached a maximal level at 10 hr with doses of 25 and 100 μg/fetus. Glucose-1-P, which was expected to increase with stimulated glycogenolysis, increased after 5 hr at a dose of 25 μg/fetus but not at 100 μg/fetus. Glucose-6-P gradually decreased from day 19 to 21 in control fetuses but this age-dependent decrease was blocked by the steroid. Glucose increased after 5 hr and remained at the same level thereafter. The steroid also decreased glycogen synthase (EC 2.4.1.11) a activity. These results indicate that betamethasone 17, 21-dipropionate suppresses glycogen accumulation in fetal rat liver, and inhibition between UDP-glucose and glycogen plays an important role in this action.