Thyroid hormones augment catecholamine-stimulated brown adipose tissue thermogenesis in the ovine fetus

The effects of exogenous changes in thyroid status on in vitro brown adipose tissue (BAT) cellular respiration and thermogenic enzymes (sodium-potassium ATP' ase and alpha-glycerophosphate dehydrogenase) were studied in fetal sheep. Thyroidectomy and insertion of a constant infusion pump followed by 8 days of infusion of either T3 (n = 7) or vehicle (n = 4) were performed in fetal lambs at 119-121 days gestation. The animals were then killed, and perirenal BAT was removed for study. T3 infusion resulted in a mean plasma T3 concentration of 322 +/- 52 ng/dl compared to levels at the limits of detection (9 ng/dl) in the vehicle-infused animals. Basal respiration values with or without ouabain were similar in the two groups. Maximum mean norepinephrine (NE; 10(-6) M)-stimulated respiration (110.2 +/- 11.6 microliter O2/10(6) cells X h) in the T3-treated group was greater than stimulated mean respiration (55.3 +/- 15.6 microliter O2/10(6) cells X h) in the untreated animals (P less than 0.02). NE-stimulated respiration in the presence of ouabain (i.e. nonsodium transport-dependent respiration) was increased in the T3-treated animals (P less than 0.01), while sodium transport-dependent respiration was not different. (Bu)2cAMP-stimulated respiration was greater in the T3-treated group (P less than 0.001), while alpha-glycerophosphate substrate respiration was not different. Mitochondrial alpha-glycerophosphate dehydrogenase and Na-K-ATPase activities were similar. These studies demonstrate that BAT catecholamine-stimulated respiration is influenced by thyroid status in the ovine fetus. The increase in both NE- and (Bu)2cAMP-stimulated respiration suggests a postreceptor effect on intracellular metabolism, though an effect on beta-adrenergic receptors also might have occurred. Neither sodium transport (NA-K-ATPase)-dependent respiration nor mitochondrial alpha-glycerophosphate dehydrogenase appear to be involved. These data suggest that the relative hyperthyroid state that occurs in the newborn of both man and sheep may be important through its effects on BAT metabolism to insure adequate temperature regulation during neonatal adaptation.