88: Effects of dexamethasone, cyclic AMP and insulin on the activity of the urea cycle enzymes in fetal liver in organ culture

Abstract

Hormonal agents are used clinically to accelerate biochemical development and enhance functional maturation of small pre-term newborn infants. Present knowledge in the area of hormonal regulation of enzyme maturation in fetal tissues is still rudimentary and needs much further exploration. We have studied the effects of dexamethasone and cyclic AMP on the activity of all five urea cycle enzymes in fetal rat liver in organ culture. After 24 and 4-8 hours in culture, dexamethasone or cyclic AMP produce a 2 to 3 fold increase in the specific activity of carbamyl phosphate synthetase, argininosuccinate synthetase (ASS), argininosuccinate lyase and arginase. Ornithine transcarbamylase is not effected by either agent. The increases in the enzyme activities can be abolished by simultaneous addition of cycloheximide. Preliminary experiments indicate that insulin antagonizes the dexamethasone induced increase of the ASS activity. Thus, the hormonal stimulation of the five urea cycle enzyme activities is not synchronous. The antagonistic effect of insulin may have clinical relevance