BETA(2)-AGONIST RITODRINE, UNLIKE NATURAL CATECHOLAMINES, ACTIVATES THERMOGENESIS PREMATURELY IN FETAL SHEEP

Prolonged administration of the beta(2)-adrenergic agonist ritodrine t o fetal sheep increases nonesterified fatty acid mobilization. To inve stigate whether changes in fetal growth or functional development of b rown adipose tissue (BAT) also occur, ritodrine was infused at 5 mu g/ min iv into eight fetal sheep (6 twins and 2 singletons at 125-128 day s of gestation) for 5 days and then at twice this rate for a further 7 -11 days. Fetal growth was reduced significantly (P < 0.02) during rit odrine infusion relative to controls (5.8 +/- 17.5 vs. 79.7 +/- 10.3 g /day), with growth of skeletal muscles ceasing. Ritodrine reduced peri renal BAT weight by 50% from 18.6 +/- 1.89 to 9.3 +/- 0.60 g (P < 0.01 ) and its lipid content by >70% from 6.5 +/- 0.96 to 1.9 +/- 0.45 g (P < 0.01). Mitochondrial protein in BAT was also less (P < 0.002), but GDP binding to uncoupling protein increased (P < 0.05). In similar exp eriments, epinephrine and norepinephrine increased plasma nonesterifie d fatty acid initially, but neither altered perirenal BAT composition, The beta(2)-adrenergic agonist ritodrine appears able to promote lipi d mobilization and thermogenesis in utero.