Autori: Dumitrescu AM, Refetoff S

Editorial: Endocr Dev, 10, p.127-139, 2007.

Rezumat:

Intracellular metabolism of thyroid hormone (TH) and availability of the active hormone T3 is regulated by three selenoprotein iodothyronine deiodinases (Ds). D1 and D2 convert the precursor T4 into the active hormone, T3. D3 is the principal inactivator of T4 and T3 to their respective metabolites, rT3 and T2. While acquired changes in D activities are common, inherited defects in humans were not known. Recently, two families with abnormal thyroid function tests, high serum T4, high rT3, low T3 and slightly increased TSH, were identified. Linkage analysis and sequencing excluded abnormalities in all 3 DIO genes, yet clinical studies showed reduced responsiveness to T4 but not to T3. Extensive search for putative defects in genes involved in D2 metabolism led to the identification of mutations in the Sec insertion sequence binding protein (SBP)2 gene, involved in the synthesis of selenoproteins, including Ds. Affected children were either homozygous or compound heterozygous for these mutations. Other selenoproteins, including glutathione peroxidase, were also reduced in affected subjects, confirming a generalized effect of the SBP2 defect. Opposite thyroid test abnormalities are found in mutations of the TH transporter MCT8, and appear to be caused by the resulting increases in D2 and D1 activities.

Cuvinte cheie: thyroid hormone, MCT8, SBP2, deiodinase, knockout mice, phenotype