title: Changes in thyroid status during perinatal development of MCT8-deficient male mice.
abstract: Patients with the monocarboxylate transporter 8 (MCT8) deficiency syndrome present with a severe psychomotor retardation and abnormal serum thyroid hormone (TH) levels, consisting of high T(3) and low T(4) and rT(3). Mice deficient in Mct8 replicate the thyroid phenotype of patients with the MCT8 gene mutations. We analyzed the serum TH levels and action in the cerebral cortex and in the liver during the perinatal period of mice deficient in Mct8 to assess how the thyroid abnormalities of Mct8 deficiency develop and to study the thyroidal status of specific tissues. During perinatal life, the thyroid phenotype of Mct8-deficient mice is different from that of adult mice. They manifest hyperthyroxinemia at embryonic day 18 and postnatal day 0. This perinatal hyperthyroxinemia is accompanied by manifestations of TH excess as evidenced by a relative increase in the expression of genes positively regulated by T3 in both the cerebral cortex and liver. An increased tissue accumulation of T(4) and T(3) and the expression of TH alternative transporters, including Lat1, Lat2, Oatp1c1, and Oatp3a1 in the cortex and Lat2 and Oatp1b2 in the liver, suggested that Mct8 deficiency either directly interferes with tissue efflux of TH or indirectly activates other transporters to increase TH uptake. This report is the first to identify that the ontogenesis of TH abnormalities in Mct8-deficient mice manifests with TH excess in the perinatal period.
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Alfonso Massimiliano
authors.initials: AM
authors.lastname: Ferrara
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Liao
authors.forename: Pilar
authors.initials: P
authors.lastname: Gil-Ibáñez
authors.forename: Teresa
authors.initials: T
authors.lastname: Marcinkowski
authors.forename: Juan
authors.initials: J
authors.lastname: Bernal
authors.forename: Roy E
authors.initials: RE
authors.lastname: Weiss
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Dumitrescu
authors.forename: Samuel
authors.initials: S
authors.lastname: Refetoff
mesh_terms: D027182:Amino Acid Transport System y+ / Q000235:genetics / Q000378:metabolism; D027241:Amino Acid Transport System y+L; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005260:Female; D027301:Fusion Regulatory Protein 1, Light Chains / Q000235:genetics / Q000378:metabolism; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism; D007453:Iodide Peroxidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D026901:Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D027501:Monocarboxylic Acid Transporters; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D027981:Symporters; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology; D014284:Triiodothyronine / Q000097:blood
chemical_list: D027182:Amino Acid Transport System y+; D027241:Amino Acid Transport System y+L; D027301:Fusion Regulatory Protein 1, Light Chains; D027381:Liver-Specific Organic Anion Transporter 1; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; C464433:Oatp2 protein, mouse; C489252:Oatp3 protein, mouse; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D027701:Organic Cation Transport Proteins; C518286:SLC7A8 protein, mouse; C484257:Slc16a2 protein, mouse; C518287:Slc7a7 protein, mouse; C498887:Slco1b2 protein, mouse; D027981:Symporters; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013972:Thyrotropin; D007453:Iodide Peroxidase; D013974:Thyroxine