Biphasic effect of basic fibroblast growth factor on 125I-human chorionic gonadotropin binding to cultured immature Leydig cells.
The present studies examined the effects of basic fibroblast growth factor (bFGF or FGF-2) on 125I-human chorionic gonadotropin (hCG) binding to cultured immature rat Leydig cells. We found that low concentrations of bFGF (0.1-1.0 ng/ml) inhibited 125I-hCG binding to cultured immature Leydig cells in a dose- and time-dependent manner; however, this inhibition was reversed partially at higher bFGF concentrations (10-200 ng/ml). The decline in 125I-hCG binding by bFGF was due to a reduction in the number of binding sites per cell and not to a change in receptor affinity for the ligand. The inclusion of 10 micrograms/ml heparin (a concentration that is reported to block bFGF binding to heparan sulfate proteoglycans) with increasing bFGF concentrations had no effect on the inhibition of 125I-hCG binding by low bFGF concentrations, but completely blocked the secondary increase in binding by higher bFGF concentrations. In addition, neither varying heparin concentrations (0.1-25 micrograms/ml) nor insulin or insulin-like growth factor-I had any effect on the inhibition of 125I-hCG binding by 1 ng/ml bFGF. These studies suggest that receptor-mediated actions of bFGF (inhibition of hCG binding by low bFGF concentrations) on cultured immature Leydig cells are unaffected by heparin; however, the secondary increase in 125I-hCG binding observed with higher bFGF concentrations (mediated by bFGF binding to heparan sulfate proteoglycans) is blocked by heparin.
Murono
E P
EP
Research Service, Dorn Veterans' Hospital, Columbia, SC.
Washburn
A L
AL
Goforth
D P
DP
Wu
N
N
D000818:Animals; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D011967:Receptors, Gonadotropin / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D002738:Chloroquine; D006063:Chorionic Gonadotropin; D016222:Fibroblast Growth Factor 2; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D006497:Heparan Sulfate; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D011509:Proteoglycans; D011967:Receptors, Gonadotropin