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Identification of Thyroid Hormone Transporters in Humans: Different Molecules Are Involved in a Tissue-Specific Manner^1,2

Department of Neurophysiology (K.F., H.A., T.N., M.O., T.S., N.A., M.Se., T.A.), First Department of Surgery (K.F., H.A., M.U., M.O., T.O., K.S., M.Su., S.M.), Department of Pediatrics (T.N., Y.K., K.I.), Second Department of Internal Medicine (T.S., S.I.), Third Department of Internal Medicine (N.A., T.S.), Department of Molecular Pharmacology (K.N.), Tohoku University School of Medicine, Sendai 980-8575, Japan; Analytical and Metabolic Research Laboratories, Sankyo Co., Ltd. (T.T.), Tokyo 140-8710, Japan; and Division of Nephrology, Faculty of Medicine, University of Tokyo (M.T.), Tokyo 113-8655, Japan

Address all correspondence and requests for reprints to: Dr. Takaaki Abe, Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8574, Japan. E-mail: takaabe{at}mail.cc.tohoku.ac.jp

We have recently identified that rat organic anion transporters, polypeptide2 (oatp2) and oatp3, both of which transport thyroid hormones. However, in humans the molecular organization of the organic anion transporters has diverged, and the responsible molecule for thyroid hormone transport has not been clarified, except for human liver-specific transporter (LST-1) identified by us. In this study we isolated and characterized a novel human organic anion transporter, OATP-E from human brain. The isolated complementary DNA encodes a polypeptide of 722 amino acids with 12 transmembrane domains. A rat counterpart, oatp-E, was also identified. Homology analysis and the phylogenetic tree analysis revealed that OATP-E/oatp-E is a subfamily of the organic anion transporter. Human OATP-E transported 3,3',5-triiodo-L-thyronine (K_m, 0.9 µM), thyronine, and rT₃ in a Na⁺-independent manner. Although the clone was isolated from the brain, OATP-E messenger RNA was abundantly expressed in various peripheral tissues. The rat counterpart, oatp-E, also transported 3,3',5-triiodo-L-thyronine. In addition, in this study we revealed that human OATP, which is exclusively expressed in the brain, transported 3,3',5-triiodo-L-thyronine (K_m, 6.5 µM), T₄ (K_m, 8.0 µM), and rT₃. These data suggest that in humans, several different molecules are involved in transporting thyroid hormone: OATP in the brain, LST-1 in the liver, and OATP-E in peripheral tissues.

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