Abstract
Iodide (I-) is crucial to thyroid function, and its regulation in thyrocytes involves ion transporters and reactive oxygen species (ROS). However, the extent of 2Cl-/H+ exchanger (ClC-3) involvement in the iodide (I-) efflux from thyrocytes remains unclear. Therefore, we examined the effects of ClC-3 on I- efflux. ClC-3 expression was found to significantly alter the serum TT3 and TT4 concentrations in mice. We further found that excess I- stimulation affected ClC-3 expression, distribution, and I- efflux in FRTL-5 cells. Immunofluorescence analyses indicated that ClC-3 mainly accumulated in the cell membrane and co-localized with β-tubulins after 24 h of excess I- treatment, and that this process depended on ROS production. Thus, ClC-3 may be involved in I- efflux at the apical pole of thyrocytes via excess I--induced ROS production and β-tubulin polymerization. Our results reveal novel insights into the role of ClC-3 in I- transport and thyroid function.
Highlights
Iodide (I−) plays a crucial role in the biosynthesis of thyroid hormones, which exert a major impact on the differentiation, growth, metabolism, and physiological function of virtually all tissues [1,2]
Several in vitro studies have reported that some anion channels/transporters expressed at the thyroid apical membrane participate in the process of I- efflux, ClC-3 remained to be characterized
We investigated the role of ClC-3 in I− efflux in thyrocytes under I− excess conditions
Summary
Iodide (I−) plays a crucial role in the biosynthesis of thyroid hormones, which exert a major impact on the differentiation, growth, metabolism, and physiological function of virtually all tissues [1,2]. As a primary source for thyroid hormone synthesis, I- can suppress its own transport and organification in thyrocytes when iodine is present in excess. This is the so-called acute WolffChaikoff effect [3,4], which requires high intracellular iodide levels (≥ 10-3 M) [5]. This transient inhibition effect may last for 24 to 48 h; subsequently, organification and thyroid hormone biosynthesis resume through the so-called "escape" phenomenon [6]. The mechanisms underlying escape from the inhibitory effect remain elusive
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