IODINE REGULATION OF ENDOTHELIN-1 GENE-EXPRESSION IN CULTURED PORCINETHYROID-CELLS - POSSIBLE INVOLVEMENT IN AUTOREGULATION OF THE THYROID

We studied the regulation of endothelin (ET)-1 gene expression in porc ine thyroid cells in cultue. First, we demonstrated prepro-ET-1 mRNA i n porcine thyroid cells. The level of the mRNA was increased by phorbo l 12-myristate 13-acetate (TPA), a protein kinase C stimulator, but wa s decreased by TSH (1 mU/mL). However, transforming growth factor-beta and interleukin-1beta had no effect. The amount of immunoreactive (ir )-ET-1 secreted from the cells was also increased by TPA and was decre ased by TSH. Next, we studied the effect of iodide, as iodide has vari ous effects on thyroid cells. NaI (100 muM) increased the prepro-ET-1 mRNA level. The effect of NaI was attenuated by 1 mM methimazole (MMI) . The amount of ir-ET-1 released from the cells was also increased by the NaI treatment and the increase was also attenuated by MMI. These o bservations indicate that ET-1 gene expression is induced by organifie d iodine compounds in thyroid cells in a manner very similar to the in hibitory actions of iodide on thyroid cell function. The protein synth esis inhibitor, cycloheximide, superinduced prepro-ET-1 mRNA within 4 h, but NaI did not. The difference between cycloheximide and NaI sugge sts that the iodine effect on the gene expression is not due to nonspe cific inhibition of protein synthesis. Together with our previous find ings that porcine thyroid cells have ET-1 receptors and that ET-1 modu lates iodine metabolism, we speculate that ET-1 produced by thyroid ce lls is involved in thyroid autoregulation including thyroid blood flow .