TITLE

IMPAIRED SELENOPROTEIN SYNTHESIS CAUSED BY SBP2 GENE MUTATIONS MANIFESTS AS AN INHERITED DEFECT IN INTRACELLULAR THYROID HORMONE METABOLISM

AUTHOR(S)
Dumitrescu, Alexandra M.; Refetoff, S.
PUB. DATE
April 2007
SOURCE
Acta Endocrinologica (1841-0987);Apr-Jun2007, Vol. 3 Issue 2, p189
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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, we identified two families with abnormal thyroid function tests: high serum T4, high rT3, low T3 and slightly increased TSH. Linkage analysis and sequencing excluded abnormalities in all 3 deiodinase genes, yet clinical studies showed reduced responsiveness to T4 but not to T3. Extensive search for putative defects in genes encoding proteins involved in the synthesis of the active D2 selenoenzyme and in its degradation by ubiquitination, led to the identification of mutations in the selenocysteine insertion sequence binding protein (SBP)2 gene, involved in the synthesis of selenoproteins, including the deiodinases. Affected children were either homozygous or compound heterozygous for SBP2 mutations. Other selenoproteins, including glutathione peroxidase and selenoprotein P were also reduced in affected subjects, confirming a generalized effect of the SBP2 defect. Insight into the consequences of SBP2 defect is novel and represents an interesting example of an epistatic effect resulting in deficiency of selenoproteins.
ACCESSION #
36320633

 

Related Articles

  • Insights into the hierarchy of selenium incorporation. Berry, Marla J // Nature Genetics;Nov2005, Vol. 37 Issue 11, p1162 

    A new study shows that defects in SECIS-binding protein 2 (SBP2), a factor required for incorporation of selenium into proteins, produce alterations in thyroid hormone metabolism in humans but none of the other effects attributed to selenium deficiency or loss of selenoproteins. This finding...

  • Toenail selenium level among healthy residents of two Polish Districts. Żukowska, J.; Bode, P.; Biziuk, M. // Journal of Radioanalytical & Nuclear Chemistry;Jun2009, Vol. 280 Issue 3, p621 

    The goal of this study was to evaluate the selenium mass fraction in toenail clippings taken from random inhabitants living in various areas of the Pomeranian (Northern Poland) and Lubuskie (Western Poland) Districts. Toenail clippings were analyzed by instrumental neutron activation analysis...

  • The Mouse Sulfate Anion Transporter Gene Sat1 (Slc26a1): Cloning, Tissue Distribution, Gene Structure, Functional Characterization, and Transcriptional Regulation Thyroid Hormone. Lee, Aven; Beck, Laurent; Markovich, Daniel // DNA & Cell Biology;Jan2003, Vol. 22 Issue 1, p19 

    Sulfate (SO[sub 4][sup 2-]) is required for bone/cartilage formation and cellular metabolism. sat-1 is a SO[sub 4][sup 2-] anion transporter expressed on basolateral membranes of renal proximal tubules, and is suggested to play an important role in maintaining SO[sub 4][sup 2-] homeostasis. As a...

  • Leptin, Dopamine, Ad-36, Ghrelin, Supplements And Other New Approaches.  // Health & Stress;2002, Issue 5, p8 

    Focuses on factors causing overweight or obesity in certain individuals. Function of metabolism in controlling calories; Introduction of obesity therapy; Role of thyroid hormones in weight reduction.

  • Thyroid hormones - obesity and metabolic syndrome. Bandurska-Stankiewicz, Elżbieta // Thyroid Research;2013, Vol. 6 Issue Suppl 2, p1 

    An abstract of the article "Thyroid hormones – obesity and metabolic syndrome" by Elż bieta Bandurska-Stankiewicz is presented.

  • Interactions of metabolic syndrome and thyroid hormones. Brabant, Georg // Thyroid Research;2013, Vol. 6 Issue Suppl 2, p1 

    An abstract of the article "Interactions of metabolic syndrome and thyroid hormones" by Georg Brabant is presented.

  • Thyroid Hormone Concentrations and Muscle Metabolism in Amenorrheic and Eumenorrheic Athletes. Harber, Vicki J.; Petersen, Stewart R.; Chilibeck, Philip D. // Canadian Journal of Applied Physiology;Jun98, Vol. 23 Issue 3, p293 

    Examines the relationship between thyroid hormone concentrations and muscle metabolism in Amenorrheic and Eumenorrheic athletes. Influence of routine training in muscle metabolism; Measurement of muscle metabolism by phosphate recovery kinetics; Estimation of energy expenditure.

  • Functional characterization of mouse fetal TnI gene promoters in myocardial cells. Du, J.; Nan, C.; Huang, J. J.; Zhang, C.; Liu, J.; Jia, P.; Abers, M.; Huang, X. P. // Journal of Biomedical Science;Sep2008, Vol. 15 Issue 5, p605 

    Two major troponin I (TnI) genes, fetal TnI (ssTnI) and adult TnI (cTnI), are expressed in the mammalian heart under the control of a developmentally regulated program. In this study, the up-stream domain (∼1,800 bp) of mouse fetal TnI gene has been cloned and characterized. There is a high...

  • Influence of Adsorption and Deproteination on Potential Free Thyroxine Reference Methods. Holm, Steen S.; Andreasen, Lisbeth; Hansen, Steen H.; Faber, Jens; Staun-Olsen, Poul // Chemical Business;May2010, Vol. 24 Issue 5, p50 

    The article presents a study which examined the effect of adsorption and deproteination on potential free thyroxine (FT4) reference methods. It states that dilution could cause too low an estimate of free thyroxine in the presence of low-affinity binding protein inhibitors. Due to the advantages...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics