Role and regulation of the fibroblast growth factor axis in human thyroid follicular cells

Division of Medical Science, University of Birmingham, Birmingham B15 2TT, United Kingdom Submitted 22 November 2002 ; accepted in final form 1 May 2003 Thyroidal levels of fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor 1 (FGFR1) are elevated in human thyroid hyperplasia. To understand the significance of this, effects of FGFR1 activation on normal human thyrocyte growth and function in vitro and the regulation of FGF-2 and FGFR1 expression have been examined. FGF-2 stimulated cell growth, as measured by cell counting, and inhibited thyroid function as measured by 125 I uptake. Sensitivity to FGF-2 disappeared after 7 days, although FGFR1 expression was maintained. Thyroid-stimulating hormone (TSH, 300 mU/l) increased FGFR1 mRNA expression within 4 h and protein expression by 8 h. Exogenous FGF-2 decreased FGFR1 protein. Endogenous FGF-2 levels were low ( 1-2 pg/µg protein), and TSH treatment decreased these by 50%. Protein kinase C (PKC) activation increased FGF-2 mRNA and FGF-2 secretion within 2 h. This effect was enhanced (4.4-fold) when cells were cultured in TSH. We conclude that TSH stimulates FGFR1 but not FGF-2 expression. PKC activation stimulates FGF-2 synthesis and secretion, and TSH synergizes with PKC activators. Increases in FGFR1 or FGF-2 or in both may contribute to goitrogenesis. thyrocyte; fibroblast growth factor-2; fibroblast growth factor receptor 1; protein kinase C; thyroid function; humans Address for reprint requests and other correspondence: M. C. Eggo, The Medical School, Univ. of Birmingham, Birmingham B15 2TT, UK (E-mail: M.C.Eggo{at}bham.ac.uk ).