How thyroid controls metabolism: a different role for triiodothyronine and for diiodothyronines

1. Although the first evidence of a relationship between the thyroid and metabolism was reported in 1895, the mechanism by which thyroid hormones influence resting metabolic rate in whole animals is still poorly understood. This paper reports an attempt to test whether diiodothyronines (T2s) and triiodothyronine (T3) have different roles in the control of resting metabolism (RM). 2. Changes in resting metabolic rate were measured in hypothyroid rats treated acutely (25 micrograms (100 g body weight)-1) either with one of the T2s or with T3. Injection of T3 induced an increase of about 35% in RM that started 25-30 h after the injection and lasted until 5-6 days after the injection, the maximal value being observed at 50-75 h. The injection of T2s evoked a temporally different pattern of response. The increases in RM started 6-12 h after the injection, had almost disappeared after 48 h, and the maximal stimulation was observed at 28-30 h. 3. When actinomycin D (an inhibitor of protein synthesis) and T3 were given together, the stimulation of RM was almost completely abolished. The simultaneous injection of actinomycin D and either of the T2s, on the other hand, did not cause any attenuation of the stimulation seen with the T2s alone. 4. Following chronic treatment (3 weeks) with either T3 or T2s there was a stimulation of organ growth only after the administration of T3. 5. Chronic administration of either T2s or T3 to hypothyroid rats significantly enhanced the oxidative capacity of each of the tissues considered. In the case of T2s the stimulation was almost the same whether it was expressed as an increase in specific activity or total tissue activity. In the case of T3 the increases were, in the main, secondary to the hypertrophic or hyperplastic effect. 6. These results indicate that T2s and T3 exert different effects on RM. The effects of T2s are rapid and possibly mediated by their direct interaction with mitochondria. Those of T3 are slower and more prolonged, and at least partly attributable to a modulation of the cellularity of tissues that are metabolically very active.