The Effects of Perchlorate on Thyroidal Gene Expression are Different from the Effects of Iodide Deficiency

Abstract

Perchlorate (ClO₄⁻), which is a ubiquitous and persistent ion, competitively interferes with iodide (I) accumulation in the thyroid, producing I deficiency (ID), which may result in reduced thyroid hormone synthesis and secretion. Human studies suggest that ClO₄⁻ presents little risk in healthy individuals; however, the precautionary principle demands that the sensitive populations of ID adults and mothers require extra consideration. In an attempt to determine whether the effects on gene expression were similar, the thyroidal effects of ClO₄⁻ (10 mg/kg) treatment for 14 d in drinking water were compared with those produced by 8 wk of ID in rats. The thyroids were collected (n = 3 each group) and total mRNA was analyzed using the Affymetrix Rat Genome 230 2.0 GeneChip. Changes in gene expression were compared with appropriate control groups. The twofold gene changes due to ID were compared with alterations due to ClO₄⁻ treatment. One hundred and eighty-nine transcripts were changed by the ID diet and 722 transcripts were altered by the ClO₄⁻ treatment. Thirty-four percent of the transcripts changed by the I-deficient diet were also altered by ClO₄⁻ and generally in the same direction. Three specific transporter genes, AQP1, NIS, and SLC22A3, were changed by both treatments, indicating that the membrane-specific changes were similar. Iodide deficiency primarily produced alterations in retinol and calcium signaling pathways and ClO₄⁻ primarily produced changes related to the accumulation of extracellular matrix proteins. This study provides evidence that ClO₄⁻, at least at this dose level, changes more genes and alters different genes compared to ID.