Pendrin: the Thyrocyte Apical Membrane Iodide Transporter?

Twyffels, Laure; Massart, C.; Golstein, Philippe; Raspé, Eric; Sande, Jacqueline Van; Dumont, Jacques Emile; Beauwens, Renaud; Kruys, Véronique

doi:10.1159/000335110

Cited by 33 publications

(21 citation statements)

References 28 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is then transferred to the follicle lumen at the apical membrane by pendrin and possibly by an additional human apical iodine transporter (Twyffels et al, 2011).…”

Section: Distribution To Tissuesmentioning

confidence: 99%

Scientific Opinion on Dietary Reference Values for iodine

Products¹

2014

EFS2

115

View full text Add to dashboard Cite

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for iodine, which are provided as Adequate Intake (AI). Iodine is essential for the synthesis of thyroid hormones. Through these hormones, iodine has an important role in energy-yielding metabolism and many other physiological processes. Iodine deficiency is associated with an increased frequency of goitre and hypothyroidism in a population. The AI for iodine is based on a large epidemiological study in European school-aged children showing that goitre prevalence is lowest for a urinary iodine concentration above around 100 µg/L. From this study, a urinary iodine concentration of ≥ 100 µg/L has been accepted as the threshold indicating sufficient iodine intake of school-aged children. In the absence of similar suitable data for other age groups it is proposed that this threshold also be applied for adults, infants and young children. Taking into account urinary volume and an absorption efficiency for iodine of 92 %, an AI of 150 µg/day is proposed for adults. For infants aged 7-11 months and for children, AIs range between 70 µg/day and 130 µg/day. For pregnant women, an AI of 200 µg/day is proposed, taking into account additional needs due to increased maternal thyroid hormone production and the iodine uptake by the fetus, placenta and amniotic fluid. The proposed AI for lactating women of 200 µg/day takes into account the existence of large iodine stores in conditions of adequate iodine status before pregnancy and considers that a full compensation for the iodine secreted in breast milk is not justified for the derivation of an AI for iodine for lactating women. Iodine is an essential nutrient for mammals, required as a mandatory structural and functional element of thyroid hormones. Through these hormones, iodine has an important role in energy-yielding metabolism and on the expression of genes that impact many physiological functions, including embryogenesis and growth, and the development of neurological and cognitive functions. © EuropeanThe clinical effects of iodine deficiency, referred to as iodine deficiency disorders, are the result of insufficient intakes leading to insufficient thyroid function. Iodine deficiency disorders are seen at all stages of development and are particularly of concern in pregnancy and infancy. Chronic iodine deficiency may lead to compensatory thyroid hypertrophy with an enlargement of the thyroid gland denoted as goitre.Intestinal absorption efficiency of ingested iodine is considered to be high (> 90 %). The thyroid is the major storage site for iodine in the body. Goitrogenous substances in foods, drinking water or cigarette smoke may inhibit the thyroidal uptake of iodide or its incorporation into the tyrosine precursors of thyroid hormones. The synthesis of normal quantities of thyroid hormones requires an adequate dietary intake of iodine. The kidney is the main route of excretion of iodine. In a steady state, th...

show abstract

“…It is then transferred to the follicle lumen at the apical membrane by pendrin and possibly by an additional human apical iodine transporter (Twyffels et al, 2011).…”

Section: Distribution To Tissuesmentioning

confidence: 99%

Scientific Opinion on Dietary Reference Values for iodine

Products¹

2014

EFS2

115

View full text Add to dashboard Cite

show abstract

“…Pendrin has been proposed as the protein mediating the step of iodide export from the cell into the follicular lumen, i.e., of iodide crossing the thyrocyte's apical membrane (3). However, several arguments indicate that pendrin is not critical for this transport (38,44) as mice deficient for pendrin are euthyroid (4,6,42) and patients affected by the Pendred syndrome, i.e., homozygotic pendrin inactivation, may develop goiters in iodine-deficient conditions but usually not before the second decade of life (3). Another pathway for iodide transport across the apical membrane must therefore be considered, and the definition of its identity and hormonal responsiveness constitutes the aim of the present study.…”

mentioning

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

View full text Add to dashboard Cite

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

show abstract

“…Pendrin may also be implicated in the alkalinization of the follicular lumen by exchanging Cl -for HCO 3 -to promote generation of follicular H 2 O 2 (50,73,74). However, no significant increase in iodide organification was seen in transgenic thyroid tissues.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Interleukin-4 in the Thyroid of Transgenic Mice Upregulates the Expression ofDuox1and the Anion Transporter Pendrin

Eskalli

Achouri

Hahn

et al. 2016

Thyroid

Self Cite

View full text Add to dashboard Cite

Background:The dual oxidases (Duox) are involved in hydrogen peroxide generation, which is essential for thyroid hormone synthesis, and therefore they are markers of thyroid function. During inflammation, cytokines upregulate DUOX gene expression in the airway and the intestine, suggesting a role for these proteins in innate immunity. It was previously demonstrated that interleukin-4 (IL-4) upregulates DUOX gene expression in thyrocytes. Although the role of IL-4 in autoimmune thyroid diseases has been studied extensively, the effects of IL-4 on thyroid physiology remain largely unknown. Therefore, a new animal model was generated to study the impact of IL-4 on thyroid function. Methods: Transgenic (Thyr-IL-4) mice with thyroid-targeted expression of murine IL-4 were generated. Transgene expression was verified at the mRNA and protein level in thyroid tissues and primary cultures. The phenotype of the Thyr-IL-4 animals was characterized by measuring serum thyroxine (T4) and thyrotropin levels and performing thyroid morphometric analysis, immunohistochemistry, whole transcriptome sequencing, quantitative reverse transcription polymerase chain reaction, and ex vivo thyroid function assays. Results: Thyrocytes from two Thyr-IL-4 mouse lines (#30 and #52) expressed IL-4, which was secreted into the extracellular space. Although 10-month-old transgenic animals had T4 and thyrotropin serum levels in the normal range, they had altered thyroid follicular structure with enlarged follicles composed of elongated thyrocytes containing numerous endocytic vesicles. These follicles were positive for T4 staining the colloid, indicating their capacity to produce thyroid hormones. RNA profiling of Thyr-IL-4 thyroid samples revealed modulation of multiple genes involved in inflammation, while no major leukocyte infiltration could be detected. Upregulated expression of Duox1, Duoxa1, and the pendrin anion exchanger gene (Slc26a4) was detected. In contrast, the iodide symporter gene Slc5a5 was markedly downregulated resulting in impaired iodide uptake and reduced thyroid hormone levels in transgenic thyroid tissue. Hydrogen peroxide production was increased in Thyr-IL-4 thyroid tissue compared with wild-type animals, but no significant oxidative stress could be detected. Conclusions: This is the first study to show that ectopic expression of IL-4 in thyroid tissue upregulates Duox1/ Duoxa1 and Slc26a4 expression in the thyroid. The present data demonstrate that IL-4 could affect thyroid morphology and function, mainly by downregulating Slc5a5 expression, while maintaining a normal euthyroid phenotype.

show abstract

Pendrin: the Thyrocyte Apical Membrane Iodide Transporter?

Cited by 33 publications

References 28 publications

Scientific Opinion on Dietary Reference Values for iodine

Scientific Opinion on Dietary Reference Values for iodine

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

Overexpression of Interleukin-4 in the Thyroid of Transgenic Mice Upregulates the Expression ofDuox1and the Anion Transporter Pendrin

Contact Info

Product

Resources

About