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.