Thyroid Hormones Augment Catecholamine- Stimulated Brown Adipose Tissue Thermogenesis in the Ovine Fetus*

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Abstract
The effects of exogenous changes in thyroid status on in vitro brown adipose tissue (BAT) cellular respiration and thermogenic enzymes (Na-K-ATPase 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 [triiodothyronine] (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 2 groups. Maximum mean norepinephrine (NE; 10-6 M)-stimulated respiration (110.2 .+-. 11.6 .mu.l O2/106 cells .cntdot. h) in the T3-treated group was greater than stimulated mean respiration (55.3 .+-. 15.6 .mu.l O2/106 cells .cntdot. h) in the untreated animals (P < 0.02). NE-stimulated respiration in the presence of ouabain (i.e., non-Na transport-dependent respiration) was increased in the T3-treated animals (P < 0.01), while Na transport-dependent respiration was not different. (Bu)2cAMP-stimulated respiration was greater in the T3-treated group (P < 0.001), while .alpha.-glycerophosphate substrate respiration was not different. Mitochondrial .alpha.-glycerophosphate dehydrogenase and Na-K-ATPase activities were similar. 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 Na transport Na-K-ATPase-dependent respiration nor mitochondrial .alpha.-glycerophosphate dehydrogenase appear to be involved. 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.