Thyroid hormone (TH) plays an essential role in the proper development of the brain and peripheral tissues. Lack of sufficient TH results in abnormal development, including mental retardation. TH transporters are necessary for the intracellular availability of TH to have access to the deiodinases and nuclear receptors inside the cell. Different specific TH transporters are known to date including the monocarboxylate transporters 8 (MCT8) and 10 (MCT10), and the organic anion transporting polypeptide 1C1 (OATP1C1). MCT8 and MCT10 are widely expressed throughout the body, whereas expression of OATP1C1 is rather restricted to specific areas in the brain and testis.
The clinical importance of TH transporters is dramatically shown in patients with mutations in MCT8, suffering from severe X-linked psychomotor retardation in combination with disturbed TH levels, especially high serum T3 levels. This disease is now referred as the Allan-Herndon-Dudley Syndrome (AHDS). Worldwide >45 families have been identified with MCT8 mutations. Most MCT8 mutations result in a complete loss of TH transport function when tested in vitro, but some mutations show significant residual activity and are associated with a somewhat milder clinical phenotype.
Different Mct8 deficient mouse strains have been generated. The analysis of these mouse mutants showed that they have the same marked disturbed TH serum levels as found in the AHDS patients. However, these mice do not show any overt neurological deficits. Apparently, mice have a different subset of TH transporters important for TH transport into the brain.
Until now, no patients have been identified with mutations in MCT10 or OATP1C1. It is expected that more TH transporters will be identified to explain the cell-specific subsets of TH transporters in normal tissue and brain.
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology