Are the effects of T3 on resting metabolic rate in euthyroid rats entirely caused by T3 itself?

Because we previously reported that T-3 and 3,5-diiodo-L-thyronine (3,5-T-2) both increase resting metabolic rate (RAM), 3,5-T-2 could be another thyroidal regulator of energy metabolism. This effect of 3,5-T-2 is evident in rats made hypothyroid by propylthiouracil and iopanoic acid, not in normal euthyroid (N) rats. Possibly, under euthyroid conditions, active 3,5T(2) may need to be formed intracellularly from a precursor such as T-3. We tested this hypothesis by giving a single injection of T-3 to N rats and comparing the time course of the variations in RMR with those of the changes in the serum and hepatic levels of 3,5-T-2. Acute injection had an evident effect on RAM, 25 h earlier, in N rats than in rats made hypothyroid by propylthiouracil and iopanoic acid, maximal values (+40%) being reached in the former at 24-26 h. In N rats, the simultaneous injection of actinomycin D with the T-3 inhibited the late part of the effect (after 24 h) more strongly than the early part (14-24 h). In serum and liver, 3,5-T-2 levels were increased significantly at 12-24 h after T-3 injection into N rats, a time at which RMR was rising rapidly to peak. These results seem to indicate that when T-3 is injected into N animals, not all the effects on RMR are attributable to T-3 itself, the early effect presumably being largely because of its in vivo deiodination to 3,5-T-2. Because the effects of T-3 and 3,5-T-2 are additive, in N rats, the two iodothyronines probably cooperate in vivo to determine the total metabolic rate.