HOW THE THYROID CONTROLS METABOLISM IN THE RAT - DIFFERENT ROLES FOR TRIIODOTHYRONINE AND DIIODOTHYRONINES

1. Although the first evidence of a relationship between the thyroid a nd metabolism was reported in 1895, the mechanism by which thyroid hor mones influence resting metabolic rate in whole animals is still poorl y understood. This paper reports an attempt to test whether diiodothyr onines (T(2)s) and triiodothyronine (T-3) have different roles in the control of resting metabolism (RM). 2. Changes in resting metabolic ra te were measured in hypothyroid rats treated acutely (25 mu g (100 g b ody-weight)(-1)) either with one of the T(2)s or with T-3. Injection o f T, 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 maxi mal value being observed at 50-75 h. The injection of T(2)s evoked a t emporally 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 T-3 were given together, the stim ulation of RM was almost completely abolished. The simultaneous inject ion of actinomycin D and either of the T(2)s, on the other hand, did n ot cause any attenuation of the stimulation seen with the T(2)s alone. 4. Following chronic treatment (3 weeks) with either T-3 or T(2)s the re was a stimulation of organ growth only after the administration of T-3. 5. Chronic administration of either T(2)s or T-3 to hypothyroid r ats significantly enhanced the oxidative capacity of each of the tissu es considered. In the case of T(2)s the stimulation was almost the sam e whether it was expressed as an increase in specific activity or tota l tissue activity. In the case of T-3 the increases were, in the main, secondary to the hypertrophic or hyperplastic effect. 6. These result s indicate that T(2)s and T-3 exert different effects on RM. The effec ts of T(2)s are rapid and possibly mediated by their direct interactio n with mitochondria. Those of T-3 are slower and more prolonged, and a t least partly attributable to a modulation of the cellularity of tiss ues that are metabolically very active.