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.