Potential of brown adipose tissue type II thyroxine 5'-deiodinase as a local and systemic source of triiodothyronine in rats.

Abstract

Previous reports suggest that a type II iodothyronine 5'-deiodinase may become the main enzymatic pathway for extrathyroidal triiodothyronine (T3) generation when the enzyme levels are sufficiently elevated and/or liver and kidney type I 5'-deiodinase activity is depressed. The present studies assessed the potential of brown adipose tissue (BAT) type II 5'-deiodinase to generate T3 for the plasma pool. BAT 5'-deiodination (BAT 5'D) was stimulated by either short- (4 h) or long-term (7 wk) cold exposure (4 degrees C). Long-term cold exposure increased thyroxine (T4) secretion 40-60% and extrathyroidal T3 production three-fold. In cold-adapted rats treated with propylthiouracil (PTU), extrathyroidal T3 production was 10-fold higher than in PTU-treated rats maintained at room temperature. Cold did not stimulate liver or kidney 5'D, but the cold-adapted rats showed a six- to eightfold higher BAT 5'D content. PTU caused greater than 95% inhibition of liver and kidney 5'D, but did not affect BAT 5'D. Thyroidectomized rats maintained on 0.8 micrograms of T4/100 g of body weight (BW) per day were acutely exposed to 4 degrees C. In rats given 10 mg of PTU/100 g of BW, 4 h of cold exposure still caused a 12-fold increase in BAT 5'D, a 2.3-fold increase in plasma T3 production, and a 4.8-fold increment in the locally produced T3 in BAT itself. All these responses were abolished by pretreatment with the alpha 1-antiadrenergic drug prazosin. Regardless of the ambient temperature, liver 5'D activity was greater than 90% inhibited by PTU. These results indicate that BAT can be a major source of plasma T3 under suitable circumstances such as acute or chronic exposure to cold. Furthermore, BAT 5'D activity affects BAT T3 content itself, suggesting that thyroid hormone may have a previously unrecognized role in augmenting the thermogenic response of this tissue to sympathetic stimulation. Such interactions may be especially important during the early neonatal period in humans, a time of marked thermogenic stress.