Fibroblast growth factor is a permissive factor mediating the cellular action of rat hypothalamic growth hormone-releasing factor.
A clonal multipeptide-secreting cell line (44-2C) was used to study the interaction of basic fibroblast growth factor (bFGF) and GRF. The experiments were carried out in cells maintained under serum-free conditions in the absence of growth factors and hormonal supplements. We have shown that in 44-2C cells, rat hypothalamic GRF (rGRF) stimulates neurotensin, calcitonin, and somatostatin secretion. bFGF is not a mitogen in the 44-2C cells, but does regulate differentiated function by a mechanism involving regulation of RNA stabilization. The results presented here show for the first time that FGF acts as a competence factor mediating the cellular action of rGRF. In FGF-pretreated cells, 4-h exposure to rGRF stimulated RNA and protein synthesis. In this cell line rGRF was biologically active at 10(-14) M, and the ED50 for rGRF-mediated RNA and protein synthesis ranged from 10(-11) to 10(-12) M. We conclude that the interaction of FGF, acting as a permissive factor, and rGRF results in a novel mechanism of action for rGRF. These findings suggest that hypophysiotropic factors affect the cellular milieu in concert with growth factors, such as bFGF.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D009490:Neurosecretory Systems / Q000187:drug effects / Q000502:physiology*; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D014316:Tritium
D000596:Amino Acids; D014316:Tritium; D005346:Fibroblast Growth Factors; D012313:RNA; D013007:Growth Hormone-Releasing Hormone