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Expression of Transforming Growth Factor-ß1, Activin A, and Their Receptors in Thyroid Follicle Cells: Negative Regulation of Thyrocyte Growth and Function¹

Department of Genetics and Pathology (Å.F., B.W., N-E.H.), Unit of Pathology, University Hospital, SE-751 85 Uppsala, Sweden; and Ludwig Institute for Cancer Research (E.P., P.t.D.), Biomedical Center, Box 595, SE-751 24 Uppsala, Sweden

Address all correspondence and requests for reprints to: Åsa Franzén, Department of Genetics and Pathology, Unit of Pathology, University Hospital, SE-751 85 Uppsala, Sweden. E-mail: asa.franzen{at}genpat.uu.se

Thyroid growth and function are intricately regulated by both positive and negative factors. In the present study, we have investigated the expression of transforming growth factor-ß (TGF-ß) superfamily members and their receptors in normal porcine thyroid follicle cells. In tissue sections of porcine thyroids, we observed an expression of TGF-ß1, activin A, and bone morphogenetic protein (BMP)-7 proteins. The staining was localized to the follicular epithelium. In affinity cross-linking experiments, TGF-ß1 was found to bind to heteromeric complexes of TGF-ß type I and type II receptors, and activin A bound most efficiently to heteromeric complexes of activin type IB and type II receptors. We were unable to detect any BMP receptors (BMPRs) in attempts to perform affinity cross-linking with BMP-7. However, expression of BMPR-IA and BMPR-II messenger RNA (mRNA) was detected by Northern blot analysis. Both TGF-ß1 and activin A, but not BMP-7, increased the phosphorylation of Smad2, induced nuclear translocation of Smad2, Smad3, and Smad4, and inhibited thyrocyte cell growth as well as TSH-stimulated cAMP response. TGF-ß1 was more potent, compared with activin A, to induce these cellular responses. Taken together, our findings indicate a role for several members of the TGF-ß family in regulation of thyroid growth and function.

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