Changes in thyroid status during perinatal development of MCT8-deficient male mice

Alfonso Massimiliano Ferrara, Xiao Hui Liao, Pilar Gil-Ibáñez, Teresa Marcinkowski, Juan Bernal, Roy E. Weiss, Alexandra M. Dumitrescu, Samuel Refetoff

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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 T3 and low T4 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. A nincreased tissue accumulation of T4 and T3 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 ofTHor 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.

Original languageEnglish (US)
Pages (from-to)2533-2541
Number of pages9
JournalEndocrinology
Volume154
Issue number7
DOIs
StatePublished - Jul 1 2013

ASJC Scopus subject areas

  • Endocrinology

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    Ferrara, A. M., Liao, X. H., Gil-Ibáñez, P., Marcinkowski, T., Bernal, J., Weiss, R. E., Dumitrescu, A. M., & Refetoff, S. (2013). Changes in thyroid status during perinatal development of MCT8-deficient male mice. Endocrinology, 154(7), 2533-2541. https://doi.org/10.1210/en.2012-2031