Transforming growth factor-Î2 (TGFÎ2) has been shown to influence the growth and differentiation of many widely varied cell types in vitro, including some that are endocrinologically active. We have investigated the previously unknown effects of this unique growth factor in the differentiated rat thyroid follicular cell line FRTL-5. The cells demonstrated specific, high affinity binding of TGFÎ2, and as with other epithelial cells, the growth of these thyroid follicular cells was potently inhibited by addition of TGFÎ2 to the culture medium. TGFÎ2 caused a significant reduction in TSH-sensitive adenylate cyclase activity in the cells. The addition of (Bu)2cAMP along with the growth factor to cultures partially reversed the characteristic morphological changes seen with TGFÎ2, but did not reverse the growth inhibition. To further investigate the possible mechanisms of the effects of TGFÎ2 on the cells, we measured the influence of the growth factor on [125I]TSH binding. TGFÎ2 did not compete for specific TSH-binding sites; however, exposure of the cells to TGFÎ2 for 12 or more h resulted in a dosedependent down-regulation of TSH receptors that was fully reversible. While cellular proliferation was potently inhibited by TGFÎ2, differentiated function, as manifest by iodine-trapping ability, was stimulated by the growth factor. This stimulation of iodine uptake was independent of, and additive to, the stimulatory effects of TSH. Finally, FRTL-5 cells in serum-free medium and in response to TSH were shown to secrete TGFÎ2-like activity that competed for [125I]TGFÎ2 in a RRA. These studies suggest that TGFÎ2 may represent an autocrine mechanism of controlling the growth response to TSH in thyroid follicular cells, while allowing the continuance of differentiated function.
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