Roles of Hydrogen Peroxide in Thyroid Physiology and Disease

Song, Yue; Driessens, Natacha; Costa, Maria José de Carvalho; Deken, Xavier De; Detours, Vincent; Corvilain, Bernard; Maenhaut, Carine; Miot, Françoise; Sande, Jacqueline Van; Many, Marie‐Christine; Dumont, Jacques Emile

doi:10.1210/jc.2007-0660

Cited by 200 publications

(163 citation statements)

References 127 publications

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“…To be oxidized and bound to the tyrosines of thyroglobulin and for the following synthesis of thyroid hormones, iodide must be first transported into the lumen of the thyroid follicle (34,44). This uptake requires a first active transport from the medium to the cytosol of the follicular cell, mediated by the basal membrane Na ϩ /I Ϫ symporter NIS, and then a passive release to the follicular lumen through the apical membrane driven by a favorable electrochemical gradient.…”

Section: Discussionmentioning

confidence: 99%

“…The question therefore arises whether other membrane proteins fulfill this role. ANO1 is expressed within the apical membrane of several chloride secreting epithelia often in parallel with another chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR); they both constitute major rate-limiting steps for secretions controlled by increased cytosolic Ca 2ϩ for ANO1 and by the cAMP cascade for the CFTR (10,34). Both channels can also mediate HCO 3 Ϫ transport; yet, only ANO1 exhibits a greater selectivity for iodide than chloride and it has recently been suggested as a potential candidate mediating iodide exit into the follicular space (41).…”

Section: Discussionmentioning

confidence: 99%

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Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte

Twyffels

Strickaert

Virreira

et al. 2014

American Journal of Physiology-Cell Physiology

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Iodide is captured by thyrocytes through the Na ϩ /I Ϫ symporter (NIS) before being released into the follicular lumen, where it is oxidized and incorporated into thyroglobulin for the production of thyroid hormones. Several reports point to pendrin as a candidate protein for iodide export from thyroid cells into the follicular lumen. Here, we show that a recently discovered Ca 2ϩ -activated anion channel, TMEM16A or anoctamin-1 (ANO1), also exports iodide from rat thyroid cell lines and from HEK 293T cells expressing human NIS and ANO1. The Ano1 mRNA is expressed in PCCl3 and FRTL-5 rat thyroid cell lines, and this expression is stimulated by thyrotropin (TSH) in rat in vivo, leading to the accumulation of the ANO1 protein at the apical membrane of thyroid follicles. Moreover, ANO1 properties, i.e., activation by intracellular calcium (i.e., by ionomycin or by ATP), low but positive affinity for pertechnetate, and nonrequirement for chloride, better fit with the iodide release characteristics of PCCl3 and FRTL-5 rat thyroid cell lines than the dissimilar properties of pendrin. Most importantly, iodide release by PCCl3 and FRTL-5 cells is efficiently blocked by T16A inh-A01, an ANO1-specific inhibitor, and upon ANO1 knockdown by RNA interference. Finally, we show that the T16A inh-A01 inhibitor efficiently blocks ATP-induced iodide efflux from in vitro-cultured human thyrocytes. In conclusion, our data strongly suggest that ANO1 is responsible for most of the iodide efflux across the apical membrane of thyroid cells.anoctamin-1; iodide release; pendrin; thyrocyte; TMEM16A

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte

Twyffels

Strickaert

Virreira

et al. 2014

American Journal of Physiology-Cell Physiology

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“…After synthesis, Tg is transported and stored in the follicular colloid of the thyrocyte (11). In the follicular lumen, the tyrosine residues of Tg undergo iodination to produce mono-(MIT) and di-iodotyrosines (DIT) catalyzed by thyroid peroxidase (12) and hydrogen peroxide (13). Subsequent coupling of these iodotyrosines produces T3 and T4 (14,15).…”

mentioning

confidence: 99%

Thyroglobulin as a Biomarker of Iodine Deficiency: A Review

Feei

Skeaff²

2014

Thyroid

135

113

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Background: Thyroglobulin, produced exclusively by the thyroid gland, has been proposed to be a more sensitive biomarker of iodine status than thyrotropin or the thyroid hormones triiodothyronine and thyroxine. However, evidence on the usefulness of thyroglobulin (Tg) to assess iodine status has not been extensively reviewed, particularly in pregnant women and adults. Summary: An electronic literature search was conducted using the Cochrane CENTRAL, Web of Science, PubMed, and Medline to locate relevant studies on Tg as a biomarker of iodine status. Since urinary iodine concentration (UIC) is the recommended method to assess iodine status in populations, only studies that clearly reported both Tg and UIC were included. For the purpose of this review, a median Tg <13 lg/L and a median UIC ‡100 lg/L (UIC ‡150 lg/L for pregnant women) were used to indicate adequate iodine status. We excluded studies conducted in subjects with either known thyroid disease or those with thyroglobulin antibodies. The search strategy and selection criteria yielded 34 articles of which nine were intervention studies. The majority of studies (six of eight) reported that iodine-deficient pregnant women had a median Tg ‡13 lg/L. However, large observational studies of pregnant women, including women with adequate and inadequate iodine status, as well as well-designed intervention trials that include both Tg and UIC, are needed. In adults, the results were equivocal because iodine-deficient adults were reported to have median Tg values of either <13 or ‡13 lg/L. Only studies in school-aged children showed that iodine-sufficient children typically had a median Tg <13 lg/L. Some of the inconsistent results may be partially explained by the use of different methodological assays and failure to assess assay accuracy using a certified reference material. Conclusions: These data suggest that Tg does hold promise as a biomarker of iodine deficiency. However, it is associated with limitations. A median Tg cutoff of 13 lg/L warrants further investigation, particularly in adults or pregnant women, as there is a lack of both observational and intervention studies in these groups.

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“…The most important effect was observed in thyroid function, what can be explained also by the fact that this gland contains considerably more Se than any other organ n C L I N I C A L S T U D I E S n n 272 n 2009 n Volume 3, Number 2 CEMED [11,21]. It is known that the presence of iodine is essential for thyroid hormone synthesis; however, it can be built into the tyrosine molecules of TG if H 2 O 2 is available in a sufficient amount [31]. Production of H 2 O 2 is a TSH-dependent process resulting in iodination of tyrosine molecules and subsequent hormone production on the apical membrane of thyrocytes in the presence of TPO.…”

Section: Discussionmentioning

confidence: 99%

“…Randox kit (Randox Laboratories Ltd, Crumlin, UK) was used for the determination of total antioxidant status (TAS) [31,32]. Thyroid volume was measured by using an ultrasound instrument (Hitachi EUB-405, Hitachi Medical Co, Tokyo, Japan) at the start and at…”

Section: Patientsmentioning

confidence: 99%

The effect of selenium therapy on autoimmune thyroiditis

Balázs¹,

Fehér²

2009

Clinical and Experimental Medical Journal

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AbbreviationsAT = autoimmune thyroiditis; n. s. = not significant; Se = selenium; T2 = di-iodothyronine; T3 = tri-iodothyronine; T4 = thyroxine; fT3 = free tri-iodothyronine; fT4 = free thyroxine; TAS = total antioxidant status; TG = thyroglobulin; TSH = thyroid-stimulating hormone; TPO = thyroid peroxidase enzyme; vs. = versus Due to its antioxidant capacity, the essential trace element selenium exerts complex effects on the endocrine and immune systems. Selenium may have an important role in autoimmune thyroid diseases because levels of free oxygen radicals are elevated during physiological thyroid hormone synthesis. Objective: To determine whether selenium therapy can influence anti-thyroid peroxidase and anti-thyroglobulin antibody levels or if there is a correlation between antioxidant capacity and autoantibody titres. Method: 132 patients with autoimmune thyroiditis were investigated in a prospective, blinded and placebo controlled study. L-thyroxine substitution therapy was administered in both groups and TSH levels remained in the normal range. The selenium treated group (70 patients, 68 female, mean age 41.4 ! 9.5 years) was compared with the placebo treated group (62 patients, 61 female, mean age 42.7 ! 8.3 years). Selenium therapy included oral administration of 100 µg L-seleno-methionine tablets twice a day for a year. Determinations of TSH, fT4 and fT3 as well as antibody levels were carried out by chemoluminescent method. Total antioxidant capacity was determined by Randox kit, and serum selenium levels were measured by atomic absorption technique. In the course of the study patients were controlled every third month and at the end of the one year long observation period. Results: Selenium levels in untreated patients were significantly lower than those in treated patients and controls. The fT3/fT4 ratio proved to be higher in patients after selenium therapy. Titres of antithyroid antibodies (mostly antithyroid peroxidase) significantly decreased at the end of the study. An inverse correlation was found between antioxidant capacity and antithyroid peroxidase levels. The volume of thyroid gland slightly diminished in treated patients. No adverse reactions were observed. Conclusion: Selenium completed with L-thyroxine is a suitable therapy of patients with autoimmune thyroiditis.

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Roles of Hydrogen Peroxide in Thyroid Physiology and Disease

Abstract: It is proposed that various pathologies can be explained, at least in part, by overproduction and lack of degradation of H2O2 (tumorigenesis, myxedematous cretinism, and thyroiditis) and by failure of the H2O2 generation or its positive control system (congenital hypothyroidism).

Cited by 200 publications

References 127 publications

Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte

Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte

Thyroglobulin as a Biomarker of Iodine Deficiency: A Review

The effect of selenium therapy on autoimmune thyroiditis

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