BASIC FIBROBLAST GROWTH-FACTOR AFFECTS DNA-SYNTHESIS AND CELL-FUNCTION AND ACTIVATES MULTIPLE SIGNALING PATHWAYS IN RAT-THYROID FRTL-5 AND PITUITARY GH3 CELLS

We have used a recombinant human basic fibroblast growth factor (basic FGF) to study its effects on cell proliferation, gene expression and accumulation of cyclic AMP (cAMP) and inositol phosphates in two well-characterized endocrine cell lines, FRTL-5 rat thyroid and GH3 rat pituitary cells. Basic FGF induced a dose-dependent increase in mitogenesis (assessed by measuring incorporation of [3H]thymidine) in FRTL-5 cells (40 ng basic FGF/ml increased mitogenesis above the control value by 2148 ± 108% (mean ± S.E.M.), but inhibited mitogenesis in GH3 cells at all doses (85 ± 4% of control with 40 ng basic FGF/ml)). Thyroglobulin mRNA concentration was increased in FRTL-5 cells (126 ± 6% of control with 40 ng basic FGF/ml) as was prolactin mRNA in GH3 cells (246 ± 11% of control with 40 ng basic FGF/ml), but GH mRNA in GH3 cells was not significantly affected by any dose of basic FGF. Intracellular cAMP was reduced by basic FGF in both FRTL-5 and GH3 cells (40 ng bFGF/ml giving 80 ± 5% of the control value in FRTL-5, and 67 ± 15% of the control value in GH3 cells) despite increased levels when FRTL-5 cells were stimulated with 150 μU TSH/ml (5645 ± 484% of control) or GH3 cells were stimulated by 10 μmol forskolin/l (3347 ± 396% of control). In both FRTL-5 and GH3 cells, accumulation of [3H]inositol phosphates was increased by 40 ng basic FGF/ml (201 ± 6 and 330 ± 51% of control values respectively). We have shown that basic FGF has different effects on mitogenesis in the two cell lines; gene expression and accumulation of inositol phosphates were increased in both, whereas the intracellular concentration of cAMP was decreased. The actions of basic FGF may be mediated through both inhibition of adenylate cyclase and hydrolysis of phosphatidyl inositol bisphosphate as has been proposed for 3T3 fibroblasts. Our data suggest that there may be a physiological role for basic FGF in both thyroid and pituitary tissue.