THYROID HORMONES-CELL INTERACTIONS

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Thyroid hormones must cross the plasma membrane to interact with nuclear or other intracellular receptors. While a saturable transport system for triiodo-thyronine (T3) has been demonstrated in many types of cells, this is less well established for thyroxine (T4). In mouse neuroblastoma cells, we found that T4 was actively and stereospecifically transported. Furthermore, L-system neutral amino acids were shown to be competitive inhibitors of both T3 and T4 transport. The inhibitory effect of phenylalanine may be of physiological importance. The binding of thyroid hormones to isolated neuroblast plasma membranes was studied by affinity labeling with bromoacetyl T3 and T4. There was selective binding of bromoacetyl T3 to a 27 kDa protein component, which may be involved in intracellular transport. 3,5-Dibromo-3'-pyridazinone-L-thyronine (L-94901), a novel thyromimetic drug, reduces hepatic cholesterol synthesis with little effect on cardiac function in rats. Kinetic analysis of T3 uptake in myoblasts, hepatoma cells and neuroblasts showed that L-94901 was a noncompetitive inhibitor of T3 uptake in all cell types, but Ki for liver and brain cells was 10-fold lower than for muscle derived cells. This differential effect on plasma membrane transport may explain the observations in the intact animal.