Thyroid-stimulating hormone increases active transport of perchlorate into thyroid cells

Endocrine Research Laboratory, Veterans Affairs Medical Center West Los Angeles, University of California Los Angeles School of Medicine, Los Angeles, California; and National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia Submitted 7 January 2008 ; acc...

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Published in:American journal of physiology: endocrinology and metabolism 2008-04, Vol.294 (4), p.E802-E806
Main Authors: Tran, Neil, Valentin-Blasini, Liza, Blount, Benjamin C, McCuistion, Caroline Gibbs, Fenton, Mike S, Gin, Eric, Salem, Andrew, Hershman, Jerome M
Format: Article
Language:English
Subjects:
Animals
Binding, Competitive
Biological Transport, Active - drug effects
Biological Transport, Active - physiology
Cell Division - drug effects
Cells
Cells, Cultured
Dose-Response Relationship, Drug
Endocrinology
Hormones
Iodides - pharmacokinetics
Metabolism
Perchlorates - pharmacokinetics
Rats
Salt
Spectrometry, Mass, Electrospray Ionization
Symporters - metabolism
Thyroid gland
Thyroid Gland - cytology
Thyroid Gland - drug effects
Thyroid Gland - metabolism
Thyrotropin - metabolism
Thyrotropin - pharmacology
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Summary:Endocrine Research Laboratory, Veterans Affairs Medical Center West Los Angeles, University of California Los Angeles School of Medicine, Los Angeles, California; and National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia Submitted 7 January 2008 ; accepted in final form 24 February 2008 Perchlorate blocks thyroidal iodide transport in a dose-dependent manner. The human sodium/iodide symporter (NIS) has a 30-fold higher affinity for perchlorate than for iodide. However, active transport of perchlorate into thyroid cells has not previously been demonstrated by direct measurement techniques. To demonstrate intracellular perchlorate accumulation, we incubated NIS-expressing FRTL-5 rat thyroid cells in various concentrations of perchlorate, and we used a sensitive ion chromatography tandem mass spectrometry method to measure perchlorate accumulation in the cells. Perchlorate caused a dose-related inhibition of 125-iodide uptake at 1–10 µM. The perchlorate content from cell lysate was analyzed, showing a higher amount of perchlorate in cells that were incubated in medium with higher perchlorate concentration. Thyroid-stimulating hormone increased perchlorate uptake in a dose-related manner, thus supporting the hypothesis that perchlorate is actively transported into thyroid cells. Incubation with nonradiolabeled iodide led to a dose-related reduction of intracellular accumulation of perchlorate. To determine potential toxicity of perchlorate, the cells were incubated in 1 nM to 100 µM perchlorate and cell proliferation was measured. Even the highest concentration of perchlorate (100 µM) did not inhibit cell proliferation after 72 h of incubation. In conclusion, perchlorate is actively transported into thyroid cells and does not inhibit cell proliferation. iodide; Na + /I – symporter Address for reprint requests and other correspondence: J. M. Hershman, Endocrinology-111D, VA Medical Center West Los Angeles, 11301 Wilshire Blvd., Los Angeles, CA 90073 (e-mail: jhershmn{at}ucla.edu )
ISSN:0193-1849
1522-1555
DOI:10.1152/ajpendo.00013.2008