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Transforming Growth Factor-ß1 Induces a Mesenchyme-Like Cell Shape without Epithelial Polarization in Thyrocytes and Inhibits Thyroid Folliculogenesis in Collagen Gel Culture

Departments of Pathology (S.T., T.N., N.Y., H.S.) and Biochemistry (S.M.), Saga Medical School, Saga 849; and the Department of Forensic Medicine and Human Genetics, Kurume University School of Medicine (N.F.), Kurume 830, Japan

Address all correspondence and requests for reprints to: Dr. Shuji Toda, Department of Pathology, Saga Medical School, Nabeshima 5–1-1, Saga 849, Japan. E-mail: toda-s{at}post.saga-med.ac.jp

Transforming growth factor-ß1 (TGFß1) induces a mesenchyme-like cell shape in some epithelial cell types. To clarify the role of TGFß1 in the morphological regulation of thyrocytes, we performed collagen gel culture of porcine thyrocytes with serum-free medium. TGFß1-nontreated cells organized follicles. In contrast, the cells treated with 10 ng/ml TGFß1 became spindle shaped, i.e. they resembled mesenchymal fibroblasts, and did not form follicles. To characterize the spindle-shaped cells, we examined the fine structures and expression of thyroglobulin (Tg) and cytoskeletal proteins using electron microscopy, immunohistochemistry, and immunoblotting. TGFß1-nontreated cells had microvilli at the apical side facing follicle lumen and had basal lamina at the basal side in contact with collagen gel. TGFß1-treated cells showed both microvilli and basal lamina at the basal side. TGFß1-nontreated cells expressed Tg, whereas TGFß1-treated cells showed no expression. TGFß1-nontreated cells barely expressed vimentin, but they expressed enough cytokeratin. TGFß1-treated cells extensively displayed vimentin along with the change in shape to become spindle-like and retained a decreased expression of cytokeratin. TSH (10 mU/ml) did not essentially influence any TGFß1 effects on the cells. These results indicate that TGFß1 induces a mesenchyme-like cell shape accompanied by cytoskeletal molecular change and the loss of both epithelial polarization and a function in thyrocytes, and that it results in inhibiting thyroid folliculogenesis with or without TSH.

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