Thyroglobulin is the precursor of the thyroid hormones, triiodothyronine and thyroxine. Because the molecular size of thyroglobulin is relatively large (660 kDa), it could have other additional functions besides serving as the precursor of the thyroid hormones. In this report, we examined the proliferative effects of thyroglobulins purified from bovine and porcine thyroid tissues on the growth of a rat thyroid follicular cell line, FRTL-5, as well as the primary culture of porcine thyroid epithelial cells. Bovine and porcine thyroglobulins stimulated the proliferation of not only FRTL-5 cells but also porcine thyroid epithelial cells in a dose-dependent manner. The proliferative effect of thyroglobulin was neutralized by an anti-thyroglobulin monoclonal antibody but not by two different anti-fibroblast growth factor antibodies. The stimulatory signal of thyroglobulin was transmitted via the phosphatidylinositol 3-kinase pathway. Also, removal of the N-linked oligosaccharides on thyroglobulin reduced the proliferative activity of porcine thyroglobulin, suggesting that the proliferative effect of thyroglobulin is in part exerted by its carbohydrate moiety. Taken together, we have demonstrated for the first time that thyroglobulin possesses proliferative effect on thyroid epithelial cells in addition to being the precursor of the thyroid hormones.
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