TY - JOUR
T1 - Identification of thyroid hormone transporters in humans
T2 - Different molecules are involved in a tissue-specific manner
AU - Fujiwara, Koh
AU - Adachi, Hisanobu
AU - Nishio, Toshiyuki
AU - Unno, Michiaki
AU - Tokui, Taro
AU - Okabe, Mitsunori
AU - Onogawa, Tohru
AU - Suzuki, Takehiro
AU - Asano, Naoki
AU - Tanemoto, Masayuki
AU - Seki, Makoto
AU - Shiiba, Kenichi
AU - Suzuki, Masanori
AU - Kondo, Yoshiaki
AU - Nunoki, Kazuo
AU - Shimosegawa, Tooru
AU - Iinuma, Kazuie
AU - Ito, Sadayoshi
AU - Matsuno, Seiki
AU - Abe, Takaaki
PY - 2001
Y1 - 2001
N2 - 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 (Km, 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 (Km, 6.5 μM), T4 (Kin, 8.0 μM), and rTs. 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.
AB - 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 (Km, 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 (Km, 6.5 μM), T4 (Kin, 8.0 μM), and rTs. 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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U2 - 10.1210/endo.142.5.8115
DO - 10.1210/endo.142.5.8115
M3 - Article
C2 - 11316767
AN - SCOPUS:17744376593
SN - 0013-7227
VL - 142
SP - 2005
EP - 2012
JO - Endocrinology
JF - Endocrinology
IS - 5
ER -