Thyroid hormone transporters in the brain

Abstract

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 T(3) 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.