Divergent patterns of immediate early gene expression in response to thyroid-stimulating hormone and insulin-like growth factor I in Wistar rat thyrocytes.
The rapid and transient induction of immediate early gene expression accompanies growth factor stimulation. TSH and insulin-like growth factor I (IGF-I) are important regulators of the thyroid follicular cell and stimulate both proliferation and differentiation. The signaling pathways induced by TSH and IGF-I are at least partially distinct. TSH uses cAMP as a second messenger, whereas the IGF-I receptor possesses protein tyrosine kinase activity. Although both agents stimulate DNA synthesis and proliferation in Wistar rat thyroid cells, they induce dramatically different patterns of immediate early gene expression. IGF-I stimulates the expression of c-fos, c-jun, junB, and egr1. In contrast, TSH stimulates c-fos and junB but not egr1 expression. TSH inhibits basal levels of c-jun expression in quiescent cells and represses serum and IGF-I-stimulated c-jun, c-fos, and egr1 expression. Consistent with these results, TSH represses serum- and phorbol ester-stimulated AP-1 activity. Although TSH and IGF-I individually stimulate DNA synthesis in thyroid cells, they exert opposing effects on the expression of some immediate early genes, including c-jun and egr1.
Tominaga
T
T
Department of Medicine, University of California at San Diego, La Jolla 92093.
Dela Cruz
J
J
Burrow
G N
GN
Meinkoth
J L
JL
D000818:Animals; D001483:Base Sequence; D002417:Cattle / Q000097:blood / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1; D005312:Fetal Blood; D015870:Gene Expression / Q000187:drug effects*; D017781:Genes, Immediate-Early; D017874:Immediate-Early Proteins; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013972:Thyrotropin / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D015335:Molecular Probes; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin; D013755:Tetradecanoylphorbol Acetate