Thyroid hormones are essential for brain development. The active
thyroid hormone, T3, binds to several products of two genes, the nuclear
thyroid hormone receptors alpha and beta, and thus regulates gene expression. Mutations in a
thyroid hormone transmembrane
transport protein, monocarboxylate transporter 8 (MCT8), underlie one of the first described
X-linked mental retardation syndromes, the
Allan-Herndon-Dudley syndrome. This discovery sparked great interest in the process of
thyroid hormone transmembrane transport. Iodothyronines are charged
amino acid derivatives and require
protein facilitators to cross cellular membranes.
Thyroid hormones are translocated across
lipid bilayers by several members of the major facilitator superfamily, including monocarboxylate
transporters, amino acid transporters, and organic
anion transporting
polypeptides. Although until recently few researchers considered
thyroid hormone transporters an important object of study, there is now a large number of candidate transporters to be reckoned with in the brain. Moreover, to finally cross the neuronal plasma membrane, any iodothyronine molecule on its way toward a neuronal nucleus has to cross consecutively the lumenal and ablumenal membranes of the capillary endothelium, enter astrocytic foot processes, and leave the astrocyte through the plasma membrane. Moreover, microglia, oligodendrocytes, and precursor and stem cells are
thyroid hormone responsive and likely express
thyroid hormone transporters. Hence, the many roles played by
thyroid hormones in the development, function, and regeneration of the nervous system are dependent on the spatiotemporal expression of several transmembrane
transport proteins.