title: A coherent organization of differentiation proteins is required to maintain an appropriate thyroid function in the Pendred thyroid.
abstract: BACKGROUND
  Pendred syndrome is caused by mutations in the gene coding for pendrin, an apical Cl-/I- exchanger.
  
  
  OBJECTIVE
  To analyze intrathyroidal compensatory mechanisms when pendrin is lacking, we investigated the thyroid of a patient with Pendred syndrome. The expression of proteins involved in thyroid hormone synthesis, markers of oxidative stress (OS), cell proliferation, apoptosis, and antioxidant enzymes were analyzed.
  
  
  RESULTS
  Three morphological zones were identified: nearly normal follicles with iodine-rich thyroglobulin in the colloid (zone 1.a), small follicles without iodine-rich thyroglobulin in lumina (zone 1.b), and destroyed follicles (zone 2). In zones 1.a, dual oxidase (Duox) and thyroid peroxidase (TPO) were localized at the apical pole, OS and cell apoptosis were absent, but ClC-5 expression was strongly increased. In zones 1.b, Duox and TPO were aberrantly present and increased in the cytosol and associated with high OS, apoptosis, cell proliferation, and increased expression of peroxiredoxin-5, catalase, and dehalogenase-1 but moderate ClC-5 expression.
  
  
  CONCLUSIONS
  In conclusion, the absence of pendrin is accompanied by increased ClC-5 expression that may transiently compensate for apical iodide efflux. In more affected follicles, Duox and TPO are relocated in the cytosol, leading to abnormal intracellular thyroid hormone synthesis, which results in cell destruction presumably because intracellular OS cannot be buffered by antioxidant defenses.
authors.affiliation: Unité de Morphologie Expérimentale, Université Catholique de Louvain, UCL-5251, 52 Avenue E. Mounier, B-1200 Brussels, Belgium.
authors.forename: Maximin
authors.initials: M
authors.lastname: Senou
authors.forename: Céline
authors.initials: C
authors.lastname: Khalifa
authors.forename: Matthieu
authors.initials: M
authors.lastname: Thimmesch
authors.forename: François
authors.initials: F
authors.lastname: Jouret
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.forename: Vincent
authors.initials: V
authors.lastname: Col
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Audinot
authors.forename: Pascale
authors.initials: P
authors.lastname: Lipnik
authors.forename: Jose C
authors.initials: JC
authors.lastname: Moreno
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Van Sande
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Dumont
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Many
authors.forename: Ides M
authors.initials: IM
authors.lastname: Colin
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Gérard
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D049109:Cell Proliferation; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism; D000074623:Dual Oxidases; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000076988:Sulfate Transporters; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000378:metabolism* / Q000503:physiopathology
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000074623:Dual Oxidases; D007453:Iodide Peroxidase; D019255:NADPH Oxidases; C431513:DUOX1 protein, human