Thyroid Hormone Transporters

Thyroid hormone is essential for the development of the brain and the nervous system. Cellular entry is required for conversion of thyroid hormones by the intracellular deiodinases and for binding of T₃ to its nuclear receptors. Several transporters capable of thyroid hormone transport have been identified. Functional expression studies using Xenopus laevis oocytes have so far identified two categories of transporters involved in thyroid hormone uptake (i.e., organic anion transporters and amino acid transporters). Among the organic anion transporters, both Na⁺{plus 45 degree rule}taurocholate cotransporting polypeptide (NTCP) and various members of the organic anion transporting polypeptide (OATP) family mediate transport of iodothyronines. Because iodothyronines are a particular class of amino acids derived from tyrosine residues, it is no surprise that some amino acid transporters have been shown to be involved in thyroid hormone transport. We have characterized monocarboxylate transporter 8 (MCT8) as a very active and specific thyroid hormone transporter, the gene of which is located on the X chromosome. MCT8 is highly expressed in liver and brain but is also widely distributed in other tissues. MCT8 shows 50% amino acid identity with a system T amino acid transporter 1 (TAT1). TAT1, also called MCT10, has been characterized to transport aromatic amino acids but no iodothyronines. We have also found that mutations in MCT8 are associated with severe X-linked psychomotor retardation and strongly elevated serum T₃ levels in young boys.