Uptake of L-triiodothyronine into human cultured lymphocytes

Abstract

The cellular uptake of [125I]L-triiodothyronine and its analogs was investigated in IM-9 human cultured lymphocytes. L-Triiodothyronine uptake was 1/2 maximal within 15 min of incubation and maximal within 45 min. The efflux of the hormone followed first order kinetics having a 1/2 time of 15 min. Treating the cells with either the mitochondrial inhibitors antimycin-A and potassium cyanide, or lowering the incubation temperature to 12.degree. C, markedly reduced uptake. [125I]L-Triiodothyronine uptake was saturable, having an affinity constant (Kd) of 110 nM. When thyroid hormone analogs were studied D-triiodothyronine and triiodothyroacetic acid (analogs known to bind avidly to nuclear receptors) competed only weakly with [125I]L-triiodothyronine for uptake. These findings indicated the importance of the intact L-alanine side chain of the thyroid hormone molecule for its uptake into lymphocytes. Other studies, with cultured rat hepatocytes, demonstrated a similar saturable uptake system for [125I]L-triiodothyronine. The uptake of thyroid hormones and their analogs into cells may be an important step in the biological actions of these hormones.