BASIC FIBROBLAST GROWTH-FACTOR - AN AUTOCRINE MITOGEN OF RAT-THYROID FOLLICULAR CELLS

Basic fibroblast growth factor (FGF) is a mitogen for the rat thyroid cell line FRTL-5. A possible autocrine role for this growth factor has been investigated in rat thyroid follicular cells both in vitro and i n vivo. We report here the synthesis and localisation of basic FGF and one of its high affinity receptors (flg) in FRTL-5 cells, shown by No rthern hybridization analysis, Western blotting, and immunohistochemis try. Two major species of basic FGF mRNA of approximately 2.2 and 7.0 kilobases and one major species of flg mRNA of approximately 4.2 kilob ases were identified in FRTL-5 cells. The basic FGF immunoreactivity o bserved histologically was attributed to a heparin-binding protein of approximately 20 kilodaltons mol wt. The physiological relevance of ba sic FGF to the thyroid is underlined by the demonstration of significa nt stores of immunoreactive protein, predominantly in the basement mem brane of thyroid follicular cells, in paraffin sections of the normal rat thyroid, although basic FGF mRNA was not detected by in situ or No rthern hybridization analysis. The mitogenic response of FRTL-5 cells to human recombinant basic FGF has been further characterized, and the factor shown to stimulate with an ED50 of 4 ng/ml. The mitogenic effe cts of exogenously supplied and endogenously produced basic FGF were s hown to be potentiated by heparin. Examination of the mitogenic activi ty of both exogenous and endogenous basic FGF and its immunoneutraliza tion in vitro suggests that locally produced basic FGF may be an impor tant autocrine regulator of thyroid follicular cell growth.