Chonnam Med J.
2000 Sep;36(3):297-306.
Effect of Lithium on Na+/I- Symporter Gene Expression in Rat Thyroid FRTL-5 Cells
- Affiliations
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- 1Department of Internal Medicine, Chonnam National University Medical School.
Abstract
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Lithium has been reported to alter thyroid function and cause goiter in some patients. To explain the mechanism of lithium action on thyroid iodide (I-) uptake at the molecular level, we studied, using functioning rat thyroid FRTL-5 cells, the effect of lithium on gene expression of Na+/I- symporter (NIS) by which I- is cotransported with Na+ into the thyroid cells. TSH-induced I- accumulation was suppressed by lithium at the concentration of 0.5 mM or higher in FRTL-5 cells. In contrast, lithium increased I- accumulation by decreasing I- release in CHO cells stably expressing a rat NIS cDNA. These results suggest that lithium could decrease NIS gene expression in FRTL-5 cells. Indeed, the TSH-induced increases in both NIS mRNA and NIS protein levels were suppressed by lithium treatment of FRTL-5 cells. Lithium also inhibited forskolin- and (Bu) 2cAMP-stimulated NIS mRNA levels as well as I- uptake by FRTL-5 cells; however, even 10 mM lithium did not affect TSH-induced cAMP production. In sum, suppression of I- transport activity by lithium in thyrocytes is partly due to a decrease in NIS gene expression, which is mediated at a step after cAMP production.