BASIC FIBROBLAST GROWTH-FACTOR REGULATES THE CONVERSION OF PRO-LUTEINIZING HORMONE-RELEASING HORMONE (PRO-LHRH) TO LHRH IN IMMORTALIZED HYPOTHALAMIC NEURONS

Growth factors are commonly associated with the regulation of cellular proliferation and differentiation. In established cells, growth facto rs can also serve as trophic agents. Immortalized LHRH neurons contain basic fibroblast growth factor (bFGF) receptors. Although these recep tors are coupled to activation of protein kinase C, and phorbol esters are strong activators of protein kinase C-stimulated LHRH release. bF GF did not influence LHRH secretion from these cells. To clarify this discrepancy, the effects of bFGF and phorbol ester on pro-LHRH biosynt hesis, protein processing, and secretion were examined in GT1-7 cells. Phorbol ester stimulated LHRH secretion, whereas bFGF either had no e ffect or stimulated LHRH release depending upon the antiserum used. Pr o-LHRH levels in lysate and medium were depressed by phorbol esters; c oncentrations in bFGF-treated cells were somewhat lower than those in unstimulated controls. HPLC analyses revealed that both agents enhance d the release of LHRH intermediate products into the medium. C-Termina lly extended forms of LHRH, especially LHRH-[Gly(11)], were prominent in medium from bFGF-stimulated neurons. Levels of LHRH were depressed relative to those in the control or phorbol ester groups. These data i ndicate that phorbol esters control the biosynthesis, secretion, and, to some extent, processing of pro-LHRH. The effects of bFGF are novel because this factor regulates processing of the prohormone so that LHR H-intermediate products are predominantly secreted instead of LHRH. By enhancing the secretion of these intermediates over that of LHRH, bFG F can control the biological activity of the decapeptide and regulate LHRH neuronal function.