title: Tissue-specific alterations in thyroid hormone homeostasis in combined Mct10 and Mct8 deficiency.
abstract: The monocarboxylate transporter Mct10 (Slc16a10; T-type amino acid transporter) facilitates the cellular transport of thyroid hormone (TH) and shows an overlapping expression with the well-established TH transporter Mct8. Because Mct8 deficiency is associated with distinct tissue-specific alterations in TH transport and metabolism, we speculated that Mct10 inactivation may compromise the tissue-specific TH homeostasis as well. However, analysis of Mct10 knockout (ko) mice revealed normal serum TH levels and tissue TH content in contrast to Mct8 ko mice that are characterized by high serum T3, low serum T4, decreased brain TH content, and increased tissue TH concentrations in the liver, kidneys, and thyroid gland. Surprisingly, mice deficient in both TH transporters (Mct10/Mct8 double knockout [dko] mice) showed normal serum T4 levels in the presence of elevated serum T3, indicating that the additional inactivation of Mct10 partially rescues the phenotype of Mct8 ko mice. As a consequence of the normal serum T4, brain T4 content and hypothalamic TRH expression were found to be normalized in the Mct10/Mct8 dko mice. In contrast, the hyperthyroid situation in liver, kidneys, and thyroid gland of Mct8 ko mice was even more severe in Mct10/Mct8 dko animals, suggesting that in these organs, both transporters contribute to the TH efflux. In summary, our data indicate that Mct10 indeed participates in tissue-specific TH transport and also contributes to the generation of the unusual serum TH profile characteristic for Mct8 deficiency.
authors.affiliation: Leibniz Institute for Age Research/Fritz Lipmann Institute (J.M., S.M., L.F., H.H.), Jena, Germany; Department of Internal Medicine (T.J.V.), Erasmus Medical Center, Rotterdam, The Netherlands; Laboratory of Comparative Endocrinology (V.M.D.), Biology Department, Katholieke Universiteit Leuven, Leuven, Belgium; Department of Endocrinology and Metabolism (A.B.), Academic Medical Center, Amsterdam, The Netherlands; Institute of Physiology and Zürich Center for Integrative Human Physiology (L.M., F.V.), University of Zürich, Zürich, Switzerland; and Leibniz Institute for Environmental Medicine (H.H.), Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Müller
authors.forename: Steffen
authors.initials: S
authors.lastname: Mayerl
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Veerle M
authors.initials: VM
authors.lastname: Darras
authors.forename: Anita
authors.initials: A
authors.lastname: Boelen
authors.forename: Lucien
authors.initials: L
authors.lastname: Frappart
authors.forename: Luca
authors.initials: L
authors.lastname: Mariotta
authors.forename: Francois
authors.initials: F
authors.lastname: Verrey
authors.forename: Heike
authors.initials: H
authors.lastname: Heuer
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D005260:Female; D005838:Genotype; D006706:Homeostasis; D007030:Hypothalamo-Hypophyseal System; D017403:In Situ Hybridization; D026901:Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D027501:Monocarboxylic Acid Transporters; D009154:Mutation; D009928:Organ Specificity; D027981:Symporters; D013961:Thyroid Gland / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood* / Q000378:metabolism
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; C509612:Slc16a10 protein, mouse; C484257:Slc16a2 protein, mouse; D027981:Symporters; D013963:Thyroid Hormones