Expression of transforming growth factor-beta 1, activin A, and their receptors in thyroid follicle cells: Negative regulation of thyrocyte growth and function

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-p (TGF-P) superfamily members and their rece ptors in normal porcine thyroid follicle cells. In tissue sections of porci ne thyroids, we observed an expression of TGF-beta 1, activin A, and bone m orphogenetic protein (BMP)-7 proteins. The staining was localized to the fo llicular epithelium. In affinity cross-linking experiments, TGF-beta 1 was found to bind to heteromeric complexes of TGF-beta type I and type II recep tors, and activin A bound most efficiently to heteromeric complexes of acti vin type IB and type II receptors. We were unable to detect any BMP recepto rs (BMPRs) in attempts to perform affinity cross-linking with BMP-7. Howeve r, expression of BMPR-IA and BMPR-II messenger RNA (mRNA) was detected by N orthern blot analysis. Both TGF-beta 1 and activin A, but not BMP-7, increa sed the phosphorylation of Smad2, induced nuclear translocation of Smad2, S mad3, and Smad4, and inhibited thyrocyte cell growth as well as TSH-stimula ted cAMP response. TGF-beta 1 was more potent, compared with activin A, to induce these cellular responses. Taken together, our findings indicate a ro le for several members of the TGF-beta family in regulation of thyroid grow th and function.