TY - JOUR
T1 - Thyroid hormone transporters in the brain
AU - Suzuki, Takehiro
AU - Abe, Takaaki
N1 - Funding Information:
1Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, and 2The 21st Century COE Program Special Research Grant from the Ministry of Education Science, Sports and Culture, Tohoku University Graduate School of Medicine, Japan
PY - 2008/3
Y1 - 2008/3
N2 - Thyroid hormone plays an essential role in proper mammalian development of the central nervous system and peripheral tissues. Lack of sufficient thyroid hormone results in abnormal development of virtually all organ systems, a syndrome termed cretinism. In particular, hypothyroidism in the neonatal period causes serious damage to neural cells and leads to mental retardation. Although thyroxine is the major product secreted by the thyroid follicular cells, the action of thyroid hormone is mediated mainly through the deiodination of T 4 to the biologically active form 3,3', 5-triiodo-L-thyronine, followed by the binding of T3 to a specific nuclear receptor. Before reaching the intracellular targets, thyroid hormone must cross the plasma membrane. Because of the lipophilic nature of thyroid hormone, it was thought that they traversed the plasma membrane by simple diffusion. However, in the past decade, a membrane transport system for thyroid hormone has been postulated to exist in various tissues. Several classes of transporters, organic anion transporter polypeptide (oatp) family, Na+/Taurocholate cotransporting polypeptide (ntcp) and amino acid transporters have been reported to transport thyroid hormones. Monocarboxylate transporter8 (MCT8) has recently been identified as an active and specific thyroid hormone transporter. Mutations in MCT8 are associated with severe X-linked psycomotor retardation and strongly elevated serum T3 levels in young male patients. Several other molecules should be contributed to exert the role of thyroid hormone in the central nervous system.
AB - Thyroid hormone plays an essential role in proper mammalian development of the central nervous system and peripheral tissues. Lack of sufficient thyroid hormone results in abnormal development of virtually all organ systems, a syndrome termed cretinism. In particular, hypothyroidism in the neonatal period causes serious damage to neural cells and leads to mental retardation. Although thyroxine is the major product secreted by the thyroid follicular cells, the action of thyroid hormone is mediated mainly through the deiodination of T 4 to the biologically active form 3,3', 5-triiodo-L-thyronine, followed by the binding of T3 to a specific nuclear receptor. Before reaching the intracellular targets, thyroid hormone must cross the plasma membrane. Because of the lipophilic nature of thyroid hormone, it was thought that they traversed the plasma membrane by simple diffusion. However, in the past decade, a membrane transport system for thyroid hormone has been postulated to exist in various tissues. Several classes of transporters, organic anion transporter polypeptide (oatp) family, Na+/Taurocholate cotransporting polypeptide (ntcp) and amino acid transporters have been reported to transport thyroid hormones. Monocarboxylate transporter8 (MCT8) has recently been identified as an active and specific thyroid hormone transporter. Mutations in MCT8 are associated with severe X-linked psycomotor retardation and strongly elevated serum T3 levels in young male patients. Several other molecules should be contributed to exert the role of thyroid hormone in the central nervous system.
KW - Amino acid transporter
KW - Cerebellum
KW - Hypothyroidism
KW - Monocarboxylate transporter
KW - Organic anion transporter polypeptide
KW - Thyroid hormone
KW - Transporter
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U2 - 10.1007/s12311-008-0029-9
DO - 10.1007/s12311-008-0029-9
M3 - Review article
C2 - 18418673
AN - SCOPUS:61449146375
VL - 7
SP - 75
EP - 83
JO - Cerebellum
JF - Cerebellum
SN - 1473-4222
IS - 1
ER -