DIVERGENT PATTERNS OF IMMEDIATE-EARLY GENE-EXPRESSION IN RESPONSE TO THYROID-STIMULATING HORMONE AND INSULIN-LIKE GROWTH-FACTOR-I IN WISTARRAT THYROCYTES

The rapid and transient induction of immediate early gene expression a ccompanies growth factor stimulation. TSH and insulin-like growth fact or I (IGF-I) are important regulators of the thyroid follicular cell a nd stimulate both proliferation and differentiation. The signaling pat hways induced by TSH and IGF-I are at least partially distinct. TSH us es cAMP as a second messenger, whereas the IGF-I receptor possesses pr otein tyrosine kinase activity. Although both agents stimulate DNA syn thesis and proliferation in Wistar rat thyroid cells, they induce dram atically 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 b asal levels of c-jun expression in quiescent cells and represses serum and IGF-I-stimulated c-jun, c-fos, and egr1 expression. Consistent wi th these results, TSH represses serum- and phorbol ester-stimulated AP -1 activity. Although TSH and IGF-I individually stimulate DNA synthes is in thyroid cells, they exert opposing effects on the expression of some immediate early genes, including c-jun and egr1.