Beta2-agonist ritodrine, unlike natural catecholamines, activates thermogenesis prematurely in fetal sheep.
Prolonged administration of the beta2-adrenergic agonist ritodrine to fetal sheep increases nonesterified fatty acid mobilization. To investigate whether changes in fetal growth or functional development of brown adipose tissue (BAT) also occur, ritodrine was infused at 5 microg/min iv into eight fetal sheep (6 twins and 2 singletons at 125-128 days 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 ritodrine infusion relative to controls (5.8 +/- 17.5 vs. 79.7 +/- 10.3 g/day), with growth of skeletal muscles ceasing. Ritodrine reduced perirenal 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 experiments, epinephrine and norepinephrine increased plasma nonesterified fatty acid initially, but neither altered perirenal BAT composition. The beta2-adrenergic agonist ritodrine appears able to promote lipid mobilization and thermogenesis in utero.
Growth and Development Unit, University of Oxford, University Field Laboratory, Wytham, Oxford OX2 8QJ, UK.
J M
JM
Bassett
M E
ME
Symonds
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000196:embryology; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology*; D005865:Gestational Age; D007262:Infusions, Intravenous; D008053:Lipid Mobilization / Q000187:drug effects; D018482:Muscle, Skeletal / Q000196:embryology; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D012312:Ritodrine / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D005230:Fatty Acids, Nonesterified; D012312:Ritodrine; D004837:Epinephrine