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Sub theme 1.4
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Workgroup leaders | Department | |
Dr. E.B. Baart | Obstetrics and Gynaecology | |
Dr. J.S.E. Laven | Obstetrics and Gynaecology | |
dr. A.P.N. Themmen | Internal Medicine |
Goals of research: general outline |
Thyroid hormone (TH) is essential for the development of virtually all tissues. The biological activity of TH is largely mediated by binding of the active hormone T3 to the nuclear T3 receptors TRα and TRβ. Three deiodinases (D1-3) and several TH transporters determine the availability of T3 for nuclear TRs. Defects in any of these proteins can have important consequences, as is illustrated by the severe psychomotor retardation in patients with inactivating mutations in MCT8, a TH transporter expressed in central neurons. This subtheme concerns the characterization of the transporters, deiodinases and TH receptors involved, the study of their regulation in ageing and disease, and the consequences of genetic variation in these TH pathway genes. |
Scientific achievements |
a. (Patho)physiological role of thyroid hormone transporters
b. Tissue-specific regulation of thyroid hormone bioactivity
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Future plans: special goals and approach |
a. (Patho)physiological role of thyroid hormone transporters
a. (Patho)physiological role of thyroid hormone transporters
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Most recent publications |
1. Friesema ECH, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, Barrett TG, Mancilla EE, Svensson J, Kester MHA, Kuiper GGJM, Balkassmi S, Uitterlinden AG, Koehrle J, Rodien P, Halestrap AP, Visser TJ. Severe X-linked psychomotor retardation caused by mutations in a thyroid hormone transporter. Lancet 2004; 364: 1435-1437. (IF: 28.41) 2. Peeters RP, van den Beld AW, Uitterlinden AG, Janssen JA, Lamberts SWJ, Visser TJ. A polymorphism in type I deiodinase (D1) is associated with circulating free IGF-I levels and body composition in humans. J Clin Endocrinol Metab 2005; 90: 256-263. (IF: 6.33) 3. Peeters RP, Wouters PJ, Kaptein E, van Toor H, Visser TJ, Van den Berghe G. Serum rT3 and T3/rT3 are early prognostic markers in critically ill patients and are associated with post-mortem tissue deiodinase activities. J Clin Endocrinol Metab 2005 90:4559-4565. (IF: 6.33) 4. Peeters RP, van der Geyten S, Wouters P, van Toor H, Kaptein E, Visser TJ, Van den Berghe G. Tissue thyroid hormone levels in critical illness. J Clin Endocrinol Metab 2005; 90: 6498-6507. (IF: 6.33) 5. Jansen J, Friesema EC, Kester MH, Milici C, Reeser M, Gruters A, Barrett TG, Mancilla EE, Svensson J, Wemeau JL, Busi da Silva Canalli MH, Lundgren J, McEntagart ME, Hopper N, Arts WF, Visser TJ. Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine. J Clin Endocrinol Metab 2007; 92: 2378-2381. (IF: 6.33) 6. van der Deure WM, Friesema ECH, de Jong FJ, de Rijke, de Jong FH, Uitterlinden AG, Breteler MM, Peeters RP, Visser TJ. Organic Anion Transporter 1B1: An Important Factor in Hepatic Thyroid Hormone and Estrogen Transport and Metabolism. Endocrinology 2008; 149:4695-4701. (IF: 4.95) 7. Van der Deure WM, Hansen PS, Peeters RP, Kyvik KO, Friesema ECH, Hegedüs L, Visser TJ. Thyroid hormone transport and metabolism by OATP1C1 and consequences of genetic variation. Endocrinology 2008; 149: 5307-5314. (IF: 4.95) 8. Friesema ECH, Jansen J, Jachtenberg JW, Visser WE, Kester MHA, Visser TJ. Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate transporter 10 (MCT10). Mol Endocrinol 2008; 22: 1357-1369. (IF: 5.39) 9. Moreno JC, Klootwijk W, van Toor H, Gestel D, Pinto G, D'Alessandro M, Lèger A, Goudie D, Polak M, Grüters A, Visser TJ. Mutations in the iodotyrosine deiodinase gene and hypothyroidism. N Eng J Med 358: 1811-1818 (2008). (IF: 50.02) 10. Kester MHA, Toussaint MJM, Punt CA, Matondo R, Aarnio AA, Darras VM, Everts ME, de Bruin A, Visser TJ. Large induction of type III deiodinase expression after partial hepatectomy in the regenerating mouse and rat liver. Endocrinology 2009; 150: 540-545. |