tailieunhanh - Báo cáo khoa học: Cell surface heparan sulfate proteoglycans Target and partners of the basic ®broblast growth factor in rat Sertoli cells

Basic ®broblast growth factor (bFGF) regulates diversi®ed biological functions in rat Sertoli cells. This report demon-strates 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. | Eur. J. Biochem. 269 502-511 2002 FEBS 2002 Cell surface heparan sulfate proteoglycans Target and partners of the basic fibroblast growth factor in rat Sertoli cells Sylvie Brucato Jean Bocquet and Corinne Villers Laboratoire de Biochimie IRBA Universite de Caen France 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 dibu-tyryl-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-stimu-lated 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. Keywords bFGF aromatase heparansulfateproteoglycans RT-PCR Sertoli cells. The basic fibroblast growth factor bFGF or FGF-2 belongs to a large FGF family of 21 structurally related members 1 . This growth factor is produced by many cell types and tissues including testis 2 . Its biological activity is pleiotropic 3 as it influences aspects of both cellular growth differentiation but also angiogenesis tissue repair and cell migration. In rat testis bFGF affects for instance Leydig and Sertoli .

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