Different intracellular and intranuclear transport of triiodothyronine enantiomers in rat skeletal myoblasts

The mechanism(s) responsible for the different biological potency of L- and D-T3 was investigated in rat L6E9 myoblasts. After incubation with intact cells at 37 C L-T3 cellular and nuclear uptakes were 91% and 70% higher than those of D-T3, respectively, but values for nuclear uptake as a fraction of cellular uptake were similar. The difference between the enantiomers was abolished at 4 C, and metabolic and endocytotic inhibitors reduced nuclear and extranuclear saturable uptake of L-T3 to a similar degree, but had little or no effect on D-T3 uptake. The affinity constants (Ka) for L- and D-T3 binding to isolated nuclei were similar, but the apparent nuclear Ka of L-T3 in intact cells was 5-fold greater than that of D-T3. The findings suggest that stereospecific transport, mainly active at the plasma membrane, occurs in rat skeletal muscle cells. This discriminative pathway of cell entry facilitates L-T3 uptake by an energy-dependent pathway not shared by D-T3 and may explain the greater potency of L-T3 than D-T3.