Role of thyroid hormone in cold-induced changes in rat brown adipose tissue mitochondria

Abstract

The role of thyroid gland in cold-induced growth of brown adipose tissue and in cold-induced adaptive changes in brown adipose tissue mitochondria was investigated. Interscapular brown adipose tissue of thyroidectomized rats maintained at 28.degree. C was of normal size (protein, cytochrome oxidase content) and its mitochondria were normal, as judged from the level of GDP binding and the polypeptide composition. (GDP binds to a 32,000 dalton polypeptide component of the inner mitochondrial membrane. This component is part of the thermogenic proton conductance pathway. The level of GDP binding is a sensitive indicator of thermogenic state of the tissue.) Brown adipose tissue mitochondria of thyroidectomized rats exposed to 4.degree. C for 15 h did not show the usual increase in GDP binding, an indication of a lack of a thermogenic response; the response was restored in thyroxine-treated thyroidectomized animals. In thyroidectomized rats treated with a low maintenance dose of thyroxine (25 .mu.g/kg, s.c., 3 times/wk) and acclimated to cold (4.degree. C) for 2 wk, a normal growth of brown adipose (increase in protein and cytochrome oxidase) and normal changes in mitochondria (increase in GDP binding and an increase in the proportion of polypeptides of MW 31,200-34,400) occurred. Treatment of intact rats with a large dose of thyroxine (1000 .mu.g/kg, s.c., per day) resulted in a large increase in wet weight, mainly due to lipid accumulation since only small increases in protein and cytochrome oxidase and no change in DNA content occurred; mitochondrial GDP binding was decreased and polypeptide composition unchanged. Thyroid hormone exerts a permissive effect on the cold-induced, noradrenaline[norepinephrine]-mediated, unmasking of GDP-binding sites in brown adipose tissue. The failure of the thyroidectomized rat to survive at 4.degree. C is probably primarily due to its inability to activate thermogenesis in its brown adipose tissue. Thyroid hormone does not appear to be involved, other than in a permissive way, in long-term cold-induced growth and mitochondrial changes in brown adipose tissue, since these occur normally in the presence of only small amounts of thyroxine in thyroidectomized rats and do not occur in intact rats treated with large amounts of thyroxine.