Identification of thyroid hormone transporters humans: Different moleculesare involved in a tissue-specific manner

We have recently identified that rat organic anion transporters, polypeptid e2 (oatp2) and oatp3, both of which transport thyroid hormones. However, in humans the molecular organization of the organic anion transporters has di verged, and the responsible molecule for thyroid hormone transport has not been clarified, except for human liver-specific transporter (LST-1) identif ied by us. In this study we isolated and characterized a novel human organi c anion transporter, OATP-E from human brain. The isolated complementary DN A encodes a polypeptide of 722 amino acids with 12 transmembrane domains. A rat counterpart, oatp-E, was also identified. Homology analysis and the ph ylogenetic 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-thyr onine (K-m, 0.9 muM), thyronine, and rT(3) in a Na+-independent manner. Alt hough the clone was isolated from the brain, OATP-E messenger RNA was abund antly 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 muM), T-4 (K-m, 8.0 muM) , and rT(3). 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.