Thyroid hormone transporters--functions and clinical implications.
The cellular influx and efflux of thyroid hormones are facilitated by transmembrane protein transporters. Of these transporters, monocarboxylate transporter 8 (MCT8) is the only one specific for the transport of thyroid hormones and some of their derivatives. Mutations in SLC16A2, the gene that encodes MCT8, lead to an X-linked syndrome with severe neurological impairment and altered concentrations of thyroid hormones. Histopathological analysis of brain tissue from patients who have impaired MCT8 function indicates that brain lesions start prenatally, and are most probably the result of cerebral hypothyroidism. A Slc16a2 knockout mouse model has revealed that Mct8 is an important mediator of thyroid hormone transport, especially T3, through the blood-brain barrier. However, unlike humans with an MCT8 deficiency, these mice do not have neurological impairment. One explanation for this discrepancy could be differences in expression of the T4 transporter OATP1C1 in the blood-brain barrier; OATP1C1 is more abundant in rodents than in primates and permits the passage of T4 in the absence of T3 transport, thus preventing full cerebral hypothyroidism. In this Review, we discuss the relevance of thyroid hormone transporters in health and disease, with a particular focus on the pathophysiology of MCT8 mutations.
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Arturo Duperier 4, 28029 Madrid, Spain.
Juan
J
Bernal
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Arturo Duperier 4, 28029 Madrid, Spain.
Ana
A
Guadaño-Ferraz
Centre for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Arturo Duperier 4, 28029 Madrid, Spain.
Beatriz
B
Morte
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D027501:Monocarboxylic Acid Transporters / Q000235:genetics* / Q000378:metabolism; D009123:Muscle Hypotonia / Q000235:genetics* / Q000378:metabolism; D009133:Muscular Atrophy / Q000235:genetics* / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D027981:Symporters; D013963:Thyroid Hormones / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; C464433:Oatp2 protein, mouse; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C090735:SLC16A2 protein, human; C473187:SLCO1C1 protein, human; C484257:Slc16a2 protein, mouse; D027981:Symporters; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D013974:Thyroxine