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2-Agonist ritodrine,
unlike natural catecholamines, activates thermogenesis prematurely
in fetal sheep
Growth and Development Unit, University of Oxford, University Field Laboratory, Wytham, Oxford OX2 8QJ; and School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, United Kingdom
Prolonged administration of the
2-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 µg/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
2-adrenergic agonist ritodrine
appears able to promote lipid mobilization and thermogenesis in utero.
perirenal brown adipose tissue; lipid mobilization; epinephrine
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