Abstract:SUMMARY
The thyroidal uptake of 36ClO4− and the effect of stable perchlorate ion and functional state of the thyroid, such as after long-term administration of propylthiouracil (PTU) or after hypophysectomy, on the uptake of 36ClO4− were studied in rats and guinea-pigs. Based on the analysis of uptake curves, radioactive inulin and sulphate spaces, and histological measurements of compartmental sizes of the thyroid, the relative concentrations of 36ClO4− in the various compartments were calculated and … Show more
“…This is in contradiction to previous studies showing that radiolabeled perchlorate was concentrated in thyroid tissue in vivo (9,10,32) and contrasts with the selectivity series based on physiological anion transport in thyroid tissue: , 34, 35). Recently, Dohan et al (14) published additional evidence of NIS-mediated active transport of perchlorate both in vivo and in vitro.…”
Tran N, Valentín-Blasini L, Blount BC, McCuistion CG, Fenton MS, Gin E, Salem A, Hershman JM. Thyroid-stimulating hormone increases active transport of perchlorate into thyroid cells.
“…This is in contradiction to previous studies showing that radiolabeled perchlorate was concentrated in thyroid tissue in vivo (9,10,32) and contrasts with the selectivity series based on physiological anion transport in thyroid tissue: , 34, 35). Recently, Dohan et al (14) published additional evidence of NIS-mediated active transport of perchlorate both in vivo and in vitro.…”
Tran N, Valentín-Blasini L, Blount BC, McCuistion CG, Fenton MS, Gin E, Salem A, Hershman JM. Thyroid-stimulating hormone increases active transport of perchlorate into thyroid cells.
“…Similar to the uptake data of Chow and Woodbury (1970), newly available data from our laboratory (Yu et al 2002) showed two distinct phases in the clearance of 36 ClO − 4 from the male rat thyroid after an IV dose. The first phase shows quick elimination, presumably diffusion from the follicle; the second phase is slower, suggesting slow release from a deep compartment (the lumen).…”
Section: Evidence For Perchlorate Transport From Thyrocytes Into the supporting
Various published data sets that investigate the potential effect of exogenous perchlorate (ClO4-) on the uptake of iodide in the thyroid and subsequent changes in thyroid hormone levels are available. In order to best use the data towards the prediction of human health effects resulting from ClO4- exposure, the available literature data must be integrated into a self-consistent, coherent, and parsimonious quantitative model based on the most likely mode of action of perchlorate effect on thyroid function. We submit that the simplest mode of action for ClO4- in the thyroid that remains consistent with all available data involves competitive inhibition of iodide transport into the thyroid follicle, transport of perchlorate into the thyroid follicle against a concentration gradient, further transport into the thyroid lumen (where it may again interfere with iodide transport), and, finally, passive diffusion back into the blood. We believe this description of perchlorate's kinetic behavior should serve as the foundation for predictive physiologically based pharmacokinetic (PBPK) models and as a working hypothesis for further experimental exploration.
“…Indeed, ClO 4 Ϫ inhibition is one of the clearest hallmarks of NIS-mediated I Ϫ transport in both the thyroid and other tissues. Mechanistically, however, to date it has remained uncertain whether ClO 4 Ϫ is a NIS blocker or a transported substrate of NIS (2,(10)(11)(12)(13)(14).…”
The Na ؉ /I ؊ symporter (NIS) is a key plasma membrane protein that mediates active I ؊ uptake in the thyroid, lactating breast, and other tissues with an electrogenic stoichiometry of 2 Na ؉ per I ؊ . In the thyroid, NIS-mediated I ؊ uptake is the first step in the biosynthesis of the iodine-containing thyroid hormones, which are essential early in life for proper CNS development. In the lactating breast, NIS mediates the translocation of I ؊ to the milk, thus supplying this essential anion to the nursing newborn.
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