title: Adrenergic activation of triiodothyronine production in brown adipose tissue.
abstract: There are several mechanisms by which homeothermic animals increase heat production, including shivering, sympathetic nervous system activation and stimulation of thyroid hormone secretion. Studies in rats have shown that increased sympathetic activity causes increased heat production in brown adipose tissue (BAT) after cold exposure or food ingestion. Acute cold exposure also increases circulating thyroid hormones which in turn stimulate cellular metabolism through induction of various enzymes. Most metabolic effects of thyroxine (T4) are thought to be due to the triiodothyronine (T3) which is produced from T4 by a process of 5' monodeiodination. There are two enzymes responsible for this reaction: type I, or propylthiouracil (PTU)-sensitive iodothyronine deiodinase (5'D-I), which is reduced in hypothyroidism, stimulated in hyperthyroidism and probably provides most of the circulating T3 in the adult rat. Type II 5'-deiodinase (5'D-II) is characteristic of brain and pituitary, is increased by thyroidectomy, is not inhibited by PTU and provides 50-80% of the intracellular T3 in these two tissues. Recently, 5'D-II activity was identified in interscapular BAT. As the sympathetic nervous system influences the metabolic activation of BAT, we have studied the effects of noradrenaline and acute cold exposure on BAT 5'D-II. We report here that both noradrenaline and cold exposure increase BAT 5'D-II through alpha 1-adrenergic receptors, whereas depletion of catecholamines with alpha-methyl-p-tyrosine (MPT) prevents the effect of cold but not that of noradrenaline. These results suggest that the sympathetic nervous system may increase T3 production in rats by stimulating BAT 5'D-II. By increasing metabolic rate, this rise in T3 would enhance the thermogenic response to sympathetic stimulation.
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D003080:Cold Temperature; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000096:biosynthesis*; D015016:Yohimbine / Q000494:pharmacology; D019805:alpha-Methyltyrosine
chemical_list: D008781:Methyltyrosines; D014284:Triiodothyronine; D015016:Yohimbine; D019805:alpha-Methyltyrosine; D011433:Propranolol; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine