Thyroid hormone transporters in health and disease

Cellular entry is required for conversion of thyroid hormone by the intracellular deiodinases and for binding of 3,3',5-triiodothyronine (T-3) to its nuclear receptors. Recently, several transporters capable of thyroid hormone transport have been identified. Functional expression studies using Xenopus laevis oocytes have demonstrated that organic anion transporters (e.g., OATPs), and L-type amino acid transporters (LATs) facilitate thyroid hormone uptake. Among these, OATP1C1 has a high affinity and specificity for thyroxine (T-4). OATP1C1 is expressed in capillaries throughout the brain, suggesting it is critical for transport of T-4 over the blood-brain barrier. We have also characterized a member of the monocarboxylate transporter family, MCT8, as a very active and specific thyroid hormone transporter. Human MCT8 shows preference for T-3 as the ligand. MCT8 is highly expressed in liver and brain but is also widely distributed in other tissues. The MCT8 gene is located on the X chromosome. Recently, mutations in MCT8 have been found to be associated with severe X-linked psychomotor retardation and strongly elevated serum T-3 levels.