Stimulation of mitogenesis in human thyroid epithelial cells by endothelin

We investigated whether a potent vasoconstrictor, endothelin, stimulated the proliferation of human thyroid epithelial cells (thyrocytes). [3H]-thymidine incorporation into normal thyrocytes and thyrocytes from patients with Graves' disease was significantly increased at 10(-9) mol/l endothelin, reaching a plateau at 10(-8) mol/l. The proliferative responses of the thyrocytes obtained from patients with Graves' disease were similar to those of normal thyrocytes. Furthermore, the cell number of thyrocytes stimulated by endothelin was increased as compared with that of unstimulated thyrocytes. Neither indomethacin nor heparin affected this endothelin-stimulated thyrocyte proliferation. When thyrocytes were cultured with both endothelin and recombinant interleukin 1 beta, there was an additive effect on thyrocyte proliferation. The Ca2+ entry blocker, verapamil, inhibited both the proliferative responses of thyrocytes to endothelin and the additive effect of endothelin and recombinant interleukin 1 beta on thyrocyte proliferation. These results suggest that endothelin functions as a growth-promoting factor for human thyrocytes, presumably through intracellular calcium influx.