Stimulation of proliferation and inhibition of function of xenotransplanted human thyroid tissue by epidermal growth factor

A stimulation of thyroid epithelial cell proliferation by epidermal growth factor (EGF) has been repeatedly reported in different in vitro systems. Furthermore, a suppression of thyroid epithelial cell function by EGF has been described in vitro. In order to investigate the effects of EGF on the thyroid in vivo, human Graves' disease tissue was transplanted to 59 nu/nu mice. EGF was given once, and over a period of 7 days 7 times intermittently or continuously by osmotic mini pumps to mice. 3-H-thymidine histoautoradiography of transplants showed an increased 3-H-thymidine incorporation of thyroid epithelial cells and mesenchymal cells, following each form of EGF application. Thyroid epithelial cell nuclear volume, which has previously been shown to be a parameter for thyroid epithelial cell function showed a decrease following EGF application. There was a tendency to a more intensive proliferation and differentiation following intermittent EGF application compared to continuous stimulation. These results demonstrate that EGF does stimulate proliferation of thyroid epithelial as well as mesenchymal cells in vivo. The growth stimulating effect of EGF is linked with a concomitant decrease of thyroid function in vivo. The latter is most likely due to the dedifferentiating action of EGF previously shown in in vitro systems.