Genes regulated by thyrotropin and iodide in cultured human thyroid follicles: analysis by cDNA microarray.

Thyrotropin (TSH) regulates a number of genes in thyrocytes, leading to iodide uptake, de novo synthesis and release of thyroid hormones, and cell proliferation, accompanied by increased blood flow. At higher doses of iodide, however, the TSH-induced increases in thyroid hormone release and blood flow are downregulated, and high iodide intake occasionally worsens autoimmune thyroiditis. To elucidate the genes involved in such effects, we cultured human thyrocytes and examined genes modulated by TSH and iodide, using a cDNA microarray study, which can analyze 2400 genes in each run. When thyroid follicles were cultured with TSH for 2 days, more than 100 genes were upregulated. These genes included those for enzymes involved in carbohydrate and lipid metabolism, adenylate and guanylate cyclases, and enzyme involved in cell proliferation. When thyroid follicles were cultured with high iodide concentrations (10(-5) M) for 24 hours, more than 100 genes were upregulated. Interesting genes were interleukin-8, IFP53, 90-kd heat shock protein, osteopontin, and intercellular adhesion molecule-1. These results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot hybridization. In summary, TSH upregulated a number of genes regulating thyroid functions. It is intriguing that thyroid follicles cultured with a high iodide concentration (10(-5) M) increased the expression levels of genes capable of modulating lymphocyte functions, even though immunocompetent cells were extensively removed by the present experimental culture conditions. Although we have analyzed only approximately 6%-8% of all human genes, the cDNA microarray study is a powerful tool to elucidate the effects of TSH and iodide on thyroid function.