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Volume 271, Number 29, Issue of July 19, 1996 pp. 17147-17151
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Thyroid Hormone Export Regulates Cellular Hormone Content and Response

(Received for publication, February 6, 1996)

Ralff C. J. Ribeiro , Ralph R. Cavalieri ^¶ , Noureddine Lomri , Cherradi M. Rahmaoui , John D. Baxter and Bruce F. Scharschmidt

From the  Metabolic Research Unit and  Gastroenterology Division, Department of Medicine, and ^¶ Veterans Affairs Medical Center, University of California, San Francisco, California 94143-0540

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 causes TH resistance in hepatoma cells. Since these cells overexpress multidrug resistance P-glycoproteins and TH extrusion and resistance are blunted by verapamil, P-glycoproteins may mediate this resistance. Verapamil-inhibitable TH efflux was also found in primary hepatocytes, cardiocytes, and fibroblasts. These findings demonstrate that TH extrusion can modulate TH availability and action in mammalian cells.

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