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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.

Thyroid Hormone Export Regulates Cellular Hormone Content and Response

(Received for publication, February 6, 1996)

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

From the Dagger  Metabolic Research Unit and par  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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