Divergent patterns of immediate early gene expression in response to thyroid-stimulating hormone and insulin-like...

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.