A coherent organization of differentiation proteins is required to maintain an appropriate thyroid function in the Pendred thyroid.
J Clin Endocrinol Metab
; 95(8): 4021-30, 2010 Aug.
Article
en En
| MEDLINE
| ID: mdl-20501687
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Transporte de Membrana
/
Glándula Tiroides
Límite:
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2010
Tipo del documento:
Article
País de afiliación:
Bélgica