Advances in pathogenesis of goitre.

Growth regulation of the thyroid has been reinvestigated using an ex vivo system of isolated porcine thyroid follicles. Not only the direct effect of TSH, EGF, IGF I as well as iodine on growth of these follicles has been investigated but also the paracrine communication of these follicles with endothelial cells and fibroblasts. The results of recently published investigations with this culture system are summarized in this article. We could demonstrate that IGF I and EGF have a dose related effect on thyroid cell proliferation, whereas TSH has no effect on thyroid cell growth, if the iodine content of follicles is kept normal. Saturation of thyroid follicles with increasing amounts of iodine (1-40 microM K1) inhibit dose dependent EGF, IGF I or fetal calf serum induced thyroid cell proliferation. Inhibition of iodide organification with PTU or MMI abolish the growth inhibitory effect of iodide indicating that an organified iodinated product is responsible for the growth inhibitory effect of iodide on thyroid cell proliferation. Thyroid follicles secrete a FGF like substance which stimulates the growth of fibroblasts as well as endothelial cells. The secretion of FGF into the culture medium is decreased during TSH stimulation and enhanced during stimulation with EGF. The pretreatment of follicles with iodide abolishes the growth promoting effect of conditioned medium from thyroid follicles on fibroblasts and endothelial cells. We conclude that local growth factors like IGF I and EGF are responsible for thyroid cell proliferation whereas TSH stimulates specific function and hypertrophy of thyroid cells.(ABSTRACT TRUNCATED AT 250 WORDS)