High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase
| Autor: | Ulrich Schweizer, Eva K. Wirth, Eddy Rijntjes, Franziska Meyer, Josef Köhrle |
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| Rok vydání: | 2015 |
| Předmět: |
Translational Thyroidology / Original Paper
medicine.medical_specialty Allan–Herndon–Dudley syndrome biology business.industry Endocrinology Diabetes and Metabolism Deiodinase Thyroid medicine.disease Severe psychomotor retardation Endocrinology medicine.anatomical_structure Internal medicine medicine biology.protein business Hormone |
| Zdroj: | European Thyroid Journal. 4:87-91 |
| ISSN: | 2235-0802 2235-0640 |
| DOI: | 10.1159/000381021 |
| Popis: | Background: The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). Objective: To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). Methods: We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results: Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Conclusions: Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated. |
| Databáze: | OpenAIRE |
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