Energy-dependent uptake of 3,5,3'-triiodo-L-thyronine in rat skeletal muscle

The uptake of [125I]T3 in rat skeletal muscle was investigated by incubating intact soleus muscles with a tracer amount of [125I]T3. At 37 C [125I]T3 uptake increased asymptotically; at 60 min the muscle contained 10% of the total [125I]T3 or 0.238 +/- 0.021% per mg wet tissue. At 0 C the [125I]T3 uptake was 1/5 of that at 37 C. The specific [125I]T3 uptake, determined by subtracting the uptake in the presence of 10 microM unlabeled T3 from the total [125I]T3 uptake, attained a plateau after 60 min. Washout experiments, done by first incubating the muscle for 60 min at 37 C or 0 C with [125I]T3 and then at 0 C for 3 h with unlabeled T3, showed that 21 +/- 2% or 58 +/- 4% of the radioactivity, respectively, was released, indicating an intracellular location of the hormone after incubation at 37 C. Addition of increasing concentrations of L-T3, D-T3 and L-T4 caused a progressive inhibition of the [125I]T3 uptake; the 50% inhibitory concentrations being 400 nM, 7 microM, and more than 15 microM, respectively. Preincubation of soleus muscles with metabolic inhibitors almost completely inhibited [125I]T3 specific uptake, with oligomycin and antimycin causing 98 +/- 4% and 81 +/- 3% reduction, respectively. Monodansylcadaverine and bacitracin, inhibitors of receptor-mediated endocytosis, reduced the specific [125I]T3 uptake in a dose-dependent manner up to 67 +/- 3% and 62 +/- 2%, respectively. These results indicate the presence of a saturable, stereospecific, and energy-dependent process responsible, at least in part, for T3 uptake in rat skeletal muscle. This specific T3 uptake may be a receptor-mediated endocytosis process.