Differential regulation of multiple c-erbA expression by thyrotropin, insulin and insulin-like growth factor I in rat thyroid FRTL-5 cells

Abstract Regulation of multiple c- erbA gene expression was studied in rat thyroid FRTL-5 cells. Two species of erbA α (α1 and α2) mRNA and one species of erbA β (β1) mRNA were identified by Northern blot analysis. Withdrawal of thyrotropin (TSH), insulin and serum from the complete medium resulted in an increase in α1 and α2 erbA mRNA levels without altering the level of erbA β1 mRNA. Readdition of TSH, N 6 ,2′- O -dibutyryl cAMP or forskolin caused a transient reduction of α1 and α2 mRNA levels (75–90%) at 3–12 h. The α1 and α2 mRNA levels were restored at 24 h. The TSH action was dose-dependent showing the half-maximal effect at around 10 −9 M. Readdition of TSH did not show any effect on β1 mRNA level. The action of TSH was not dependent on ongoing protein synthesis but required ongoing transcription. Inhibitors of thyroid hormone biosynthesis, propylthiouracil and methylmercaptoimidazole, did not show any effect on TSH action. Readdition of insulin or insulin-like growth factor I (IGF-I) caused a dose-dependent reduction of α1 and α2 mRNA levels without any effect on β1 mRNA level. Their action was slower than TSH and persistent. The actions of insulin and IGF-I were dependent on both ongoing translation and transcription. These results indicate that TSH and insulin/IGF-I reduce levels of c- erbA α1 and α2 mRNA possibly by two distinct mechanisms without altering c- erbA β1 mRNA level in FRTL-5 cells.