Basic fibroblast growth factor affects DNA synthesis and cell function and activates multiple signalling pathways in...

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 microU TSH/ml (5645 +/- 484% of control) or GH3 cells were stimulated by 10 mumol forskolin/l (3347 +/- 396% of control). In both FRTL-5 and GH3 cells, accumulation of [3H]inositol phosphates were increased by 40 ng basic FGF/ml (201 +/- 6 and 330 +/- 51% of control values respectively).(ABSTRACT TRUNCATED AT 250 WORDS)