title: Modulation of thyroid hormone concentrations in serum of rats coadministered with perchlorate and iodide-deficient diet.
abstract: Perchlorate can perturb thyroid hormone (TH) homeostasis by competitive inhibition of iodide uptake by the thyroid gland. Until recently, the effects of perchlorate on TH homeostasis were examined by measuring serum concentrations of THs by immunoassay (IA) methods. IA methods are sensitive, but for TH analysis they are compromised by lack of adequate specificity. In this study, we determined the concentrations of six THs: L-thyroxine (T₄), 3,3',5-triiodo-L-thyronine (T₃), 3,3',5'-triiodo-L-thyronine (rT₃), 3,5-diiodo-L-thyronine, 3,3'-diiodo-L-thyronine, and 3-iodo-L-thyronine in the serum of rats administered perchlorate by isotope (¹³C₆-T₄)-dilution liquid chromatography-tandem mass spectrometry. The method recoveries for THs spiked into a serum matrix were between 97.0% and 115%, with a coefficient of variation of 2.1% to 9.4%. Rats were placed on an iodide-deficient or iodide-sufficient diet for 2.5 months, and for the last 2 weeks of that period they were provided drinking water either without or with perchlorate (10 mg/kg body weight/day). No significant differences in serum concentrations of T₃ and T₄ were observed between rats given iodide-deficient and iodide-sufficient diets for 2 or 2.5 months. After 24 h of perchlorate exposure, significantly lower concentrations of T₃ and T₄ were found in the serum of rats administered the iodide-deficient diet but not in rats administered the iodide-sufficient diet. However, after 2 weeks of perchlorate exposure, TH levels in rats fed the iodide-sufficient diet were also significantly lower than those in control rats. Our results suggest that perchlorate affects TH homeostasis and that such effects are more pronounced under iodide-deficient nutrition.
authors.affiliation: Wadsworth Center, New York State Department of Health, Empire State Plaza, P.O. Box 509, Albany, NY 12201-0509, USA.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kunisue
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Fisher
authors.forename: Kurunthachalam
authors.initials: K
authors.lastname: Kannan
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004785:Environmental Pollutants / Q000494:pharmacology*; D007454:Iodides / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D010472:Perchlorates / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013974:Thyroxine / Q000097:blood* / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D007454:Iodides; D010472:Perchlorates; D013974:Thyroxine; C494474:perchlorate