THYROID-HORMONE EXPORT REGULATES CELLULAR HORMONE CONTENT AND RESPONSE

Actions of thyroid hormones (THs) are determined by intracellular free hormone concentration, Here we report that enhanced TH extrusion via a saturable, cold-sensitive mechanism lowers intracellular TH and caus es TH resistance in hepatoma cells, Since these cells overexpress mult idrug resistance P-glycoproteins and TH extrusion and resistance are b lunted by verapamil, P-glycoproteins may mediate this resistance, Vera pamil-inhibitable TH efflux was also found in primary hepatocytes, car diocytes, and fibroblasts. These findings demonstrate that TH extrusio n can modulate TH availability and action in mammalian cells.