1. In hypothyroid rats, we determined the effects of administration of
different doses of 3,3',5-triiodo-L-thyronine (T-3), 3,3'-diiodo-L-th
yronine (3,3'-T-2) and 3,5-diiodo-L-thyronine (3,5-T-2) ('T-2 isomers'
refers specifically to these latter two isomers throughout this paper
) on resting metabolism (RM) and on the oxidative capacity (measured a
s cytochrome oxidase activity) of tissues that are metabolically very
active. 2. The T-2 isomers induced a dose-dependent calorigenic effect
when injected I.P. into hypothyroid rats. The increase in RM was alre
ady evident at a dose of 2.5 mu g (100 g body wt)(-1), and the greates
t effect was observed at the highest dose, 10 mu g (100 g body wt)(-1)
when RM reached a value not significantly different from that of the
euthyroid controls (1.92 +/- 0.08 and 1.93 +/- 0.13 (1 O-2) kg(-1) h(-
1) for 3,5-T-2 and 3,3'-T-2, respectively, vs. 2.1 +/- 0.12 (1 O-2) kg
(-1) h(-1) for euthyroid controls). T-3 administration restored RM to
normal euthyroid values, even at a dose of 2.5 mu g (100 g body wt)(-1
).3. The effect of T-2 isomers on RM was paralleled by an increase in
the oxidative capacity of tissues that are metabolically very active (
liver, skeletal muscle, brown adipose tissue (BAT) and heart). The inc
reases were between 33% (liver + 3,3'-T-2) and 63% (muscle + 3,3'-T-2)
. By contrast, T-3 induced its greatest effect on the liver, with a sm
aller effect on skeletal muscle, but no significant stimulation in hea
rt and BAT, whatever the dose. 4. These results suggest that T-2 isome
rs might be mediators of the direct thyroid hormone regulation of ener
gy metabolism.