Reference : A coherent organization of differentiation proteins is required to maintain an approp...
Scientific journals : Article
Human health sciences : Endocrinology, metabolism & nutrition
A coherent organization of differentiation proteins is required to maintain an appropriate thyroid function in the Pendred thyroid.
Senou, Maximin [> >]
Khalifa, Celine [> >]
Thimmesch, Matthieu [> >]
JOURET, François mailto [Centre Hospitalier Universitaire de Liège - CHU > > Néphrologie >]
Devuyst, Olivier [> >]
Col, Vincent [> >]
Audinot, Jean-Nicolas [> >]
Lipnik, Pascale [> >]
Moreno, Jose C. [> >]
Van Sande, Jacqueline [> >]
Dumont, Jacques E. [> >]
Many, Marie-Christine [> >]
Colin, Ides M. [> >]
Gerard, Anne-Catherine [> >]
Journal of Clinical Endocrinology and Metabolism
Yes (verified by ORBi)
United States
[en] Apoptosis/genetics ; Blotting, Western ; Cell Proliferation ; Chloride Channels/genetics/metabolism ; Female ; Humans ; Immunohistochemistry ; Iodide Peroxidase/genetics/metabolism ; Membrane Transport Proteins/genetics/metabolism ; Middle Aged ; NADPH Oxidase/genetics/metabolism ; Oxidative Stress/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Thyroid Function Tests ; Thyroid Gland/metabolism/physiopathology
[en] CONTEXT: 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. CONCLUSION: 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.

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