Differential regulation of multiple c-erbA expression by thyrotropin, insulin and insulin-like growth factor I in rat thyroid FRTL-5 cells.
Regulation of multiple c-erbA gene expression was studied in rat thyroid FRTL-5 cells. Two species of erbA alpha (alpha 1 and alpha 2) mRNA and one species of erbA beta (beta 1) mRNA were identified by Northern blot analysis. Withdrawal of thyrotropin (TSH), insulin and serum from the complete medium resulted in an increase in alpha 1 and alpha 2 erbA mRNA levels without altering the level of erbA beta 1 mRNA. Readdition of TSH, N6,2'-O-dibutyryl cAMP or forskolin caused a transient reduction of alpha 1 and alpha 2 mRNA levels (75-90%) at 3-12 h. The alpha 1 and alpha 2 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 beta 1 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 alpha 1 and alpha 2 mRNA levels without any effect on beta 1 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 alpha 1 and alpha 2 mRNA possibly by two distinct mechanisms without altering c-erbA beta 1 mRNA level in FRTL-5 cells.
Kamikubo
K
K
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599.
Nayfeh
S N
SN
Chae
C B
CB
D000818:Animals; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D013972:Thyrotropin / Q000494:pharmacology*; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000502:physiology
D007328:Insulin; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D005576:Colforsin; D003994:Bucladesine; D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin; D003513:Cycloheximide