Iodine Regulation of Endothelin-1 Gene Expression in Cultured Porcine Thyroid Cells: Possible Involvement in Autoregulation of the Thyroid

Abstract

We studied the regulation of endothelin (ET)-l gene expression in porcine thyroid cells in cultue. First, we demonstrated prepro-ET-1 mRNA in porcine thyroid cells. The level of the mRNA was increased by phorbol 12-myristate 13-acetate (TPA), a protein kinase C stimulator, but was decreased by TSH (1 mU/mL). However, transforming growth factor-β and interleukin-lβ had no effect. The amount of immunoreactive (ir)-ET-l secreted from the cells was also increased by TPA and was decreased by TSH. Next, we studied the effect of iodide, as iodide has various effects on thyroid cells. Nal (100 μM) 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 observations indicate that ET-1 gene expression is induced by organified iodine compounds in thyroid cells in a manner very similar to the inhibitory actions of iodide on thyroid cell function. The protein synthesis inhibitor, cycloheximide, superinduced prepro-ET-1 mRNA within 4 h, but NaI did not. The difference between cycloheximide and NaI suggests that the iodine effect on the gene expression is not due to nonspecific inhibition of protein synthesis. Together with our previous findings that porcine thyroid cells have ET-1 receptors and that ET-1 modulates iodine metabolism, we speculate that ET-1 produced by thyroid cells is involved in thyroid autoregulation including thyroid blood flow.