Cell surface heparan sulfate proteoglycans: target and partners of the basic fibroblast growth factor in rat Sertoli cells.

Basic fibroblast growth factor (bFGF) regulates diversified biological functions in rat Sertoli cells. This report demonstrates that bFGF inhibits steroidogenesis in developing rat Sertoli cells. Follicle stimulating hormone (FSH)-stimulated estradiol production was reduced by bFGF. Moreover, the amount of cytochrome P450 aromatase, responsible for the irreversible transformation of androgens into estrogens, is decreased by bFGF at the transcriptional level. The bFGF inhibitory effect was also observed in the presence of dibutyryl-cAMP, cholera toxin or RO-20-1724, all inducing high levels of cAMP, the second messenger of FSH. Heparan sulfate proteoglycans (HSPGs) were shown to be required as cofactors for bFGF signaling. Indeed, sodium chlorate, described to drastically decrease proteoglycan sulfation, abolishes the bFGF downregulation of FSH-stimulated estradiol synthesis previously observed. Glypican-1, syndecan-1 and -4, potential bFGF coreceptors, are mainly regulated at the transcriptional level. This report shows that the bFGF regulation of their expression specifically depends on the nature of HSPG and of the Sertoli cell developmental stage. In conclusion, HSPG are partners and the target of bFGF in rat Sertoli cells.