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Thyroid Hormone Transport by the Rat Fatty Acid Translocase

Department of Veterinary Anatomy and Physiology, Utrecht University (H.H.A.G.M.v.d.P., M.E.E.), 3508 TD Utrecht, The Netherlands; Department of Internal Medicine, Erasmus University Medical Center (E.C.H.F., T.J.V.), 3000 DR Rotterdam, The Netherlands; and Department of Physiology and Biophysics, State University of New York (N.A.A.), Stony Brook, New York 11733

Address all correspondence and requests for reprints to: Theo J. Visser, Ph.D., Department of Internal Medicine, Room Ee502, Erasmus University Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: visser{at}inw3.azr.nl.

We examined the hypothesis that rat fatty acid translocase (rFAT) mediates the cellular uptake of T₃ and other iodothyronines. Uninjected Xenopus laevis oocytes and oocytes injected 4 d previously with rFAT cRNA were incubated for 60 min at 25 C in medium containing 0.01–10 µM [¹²⁵I]T₃ and 0.1% BSA, or 1–100 µM [³H]oleic acid and 0.5% BSA. Injection of rFAT cRNA resulted in a 1.9-fold increase in uptake of T₃ (10 nM) and a 1.4-fold increase in uptake of oleic acid (100 µM). Total T₃ uptake was lower in the presence than in the absence of BSA, but relative to the free T₃ concentration, uptake was increased by BSA. The fold induction of T₃ uptake by rFAT was not influenced by BSA. By analyzing uptake as a function of the ligand concentration, we estimated a K_m value of 3.6 µM for (total) T₃ and 56 µM for (total) oleic acid. In addition to T₃, rFAT mediates the uptake of T₄, rT₃, 3,3'-diiodothyronine, and T₃ sulfate. The injection of human type III deiodinase cRNA with or without rFAT cRNA resulted in the complete deiodination of T₃ taken up by the oocytes, indicating that T₃ is indeed transported to the cytoplasm. In conclusion, our results demonstrate transport of T₃ and other iodothyronines by rFAT.

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