Expression of transforming growth factor-beta1, 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-beta (TGF-beta) super-family members and their receptors in normal porcine thyroid follicle cells. In tissue sections of porcine thyroids, we observed an expression of TGF-beta1, activin A, and bone morphogenetic protein (BMP)-7 proteins. The staining was localized to the follicular epithelium. In affinity cross-linking experiments, TGF-beta1 was found to bind to heteromeric complexes of TGF-beta 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-beta1 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-beta1 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-beta family in regulation of thyroid growth and function.
Franzén
A
A
Department of Genetics and Pathology, University Hospital, Uppsala, Sweden. asa.franzen@genpat.uu.se
Piek
E
E
Westermark
B
B
ten Dijke
P
P
Heldin
N E
NE
D029404:Activin Receptors; D028341:Activins; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D007265:Inhibins / Q000378:metabolism*; D008024:Ligands; D017978:Receptors, Growth Factor / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D012016:Reference Values; D015398:Signal Transduction / Q000502:physiology; D051899:Smad2 Protein; D051900:Smad3 Protein; D013552:Swine; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D008024:Ligands; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D029404:Activin Receptors