title: Thyroid function is maintained despite increased oxidative stress in mice lacking selenoprotein biosynthesis in thyroid epithelial cells.
abstract: OBJECTIVE
  We have tested the hypothesis that selenium (Se)-containing antioxidative enzymes protect thyroid epithelial cells from oxidative damage associated with enzymatic production of hydrogen peroxide required for thyroid hormone biosynthesis. Thyroid epithelial cells therefore express antioxidative enzymes, including catalase, peroxiredoxins, thioredoxin reductases, and glutathione peroxidases (GPxs). The latter two enzyme families contain highly active peroxide-degrading enzymes that carry selenocysteine (Sec) in their active centers. Since low Se status has been associated with thyroid disorders, selenoproteins are considered essential for thyroid integrity and function. We have conditionally inactivated selenoprotein biosynthesis in thyrocytes by targeting Sec tRNA.
  
  
  RESULTS
  Constitutive and inducible Cre/loxP-mediated recombination of tRNA([Ser]Sec) drastically reduced activities of selenoenzymes GPx and type I-deiodinase in thyroid extracts. Immunohistochemical staining revealed increased 4-hydroxynonenal and 3-nitro-tyrosine levels consistent with increased oxidative stress. However, gross thyroid morphology remained intact for at least 6 months after recombination. Circulating thyroid hormone levels remained normal in mutant mice, while thyrotropin (TSH) levels were moderately elevated. Challenging mutant mice with low iodine diet increased TSH, but did not lead to destruction of selenoprotein-deficient thyroids.
  
  
  METHODS
  This is the first report probing the assumed physiological roles of selenoproteins in the thyroid using a genetic loss-of-function approach.
  
  
  CONCLUSIONS
  We conclude that selenoproteins protect thyrocytes from oxidative damage and modulate thyroid hormone biosynthesis, but are not essential for thyrocyte survival.
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Jazmin
authors.initials: J
authors.lastname: Chiu-Ugalde
authors.forename: Eva K
authors.initials: EK
authors.lastname: Wirth
authors.forename: Marc O
authors.initials: MO
authors.lastname: Klein
authors.forename: Remy
authors.initials: R
authors.lastname: Sapin
authors.forename: Noelia
authors.initials: N
authors.lastname: Fradejas-Villar
authors.forename: Kostja
authors.initials: K
authors.lastname: Renko
authors.forename: Lutz
authors.initials: L
authors.lastname: Schomburg
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schweizer
mesh_terms: D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism; D051140:Selenoproteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism*
chemical_list: D051140:Selenoproteins; D054464:Peroxiredoxins; D002374:Catalase; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase