Follicle-stimulating hormone induces transient expression of the protooncogene c-fos in primary Sertoli cell cultures.

The expression of the protooncogene c-fos has been associated with the transduction of cell surface stimuli into changes in nuclear function. To evaluate the possibility that this protooncogene plays a role in the gonadotropin-dependent gene regulation, the effect of FSH on the expression of c-fos was studied in primary Sertoli cell cultures. Sertoli cells were stimulated for different time intervals with FSH and c-fos mRNA levels measured by Northern RNA blot analysis. FSH treatment increased c-fos mRNA transiently with a maximal stimulation reached in 1 h. The level of c-fos mRNA returned to basal level within 4-6 h. The induction of c-fos mRNA was dependent on the concentration of FSH used with an ED50 of 3-5 ng/ml ovine FSH-16. A similar increase in c-fos expression was induced with highly purified hFSH. The c-fos mRNA was also elevated after treatment of the Sertoli cell with (Bu)2cAMP and forskolin. (Bu)2cAMP treatment led to a sustained induction of c-fos mRNA, with increased mRNA levels being maintained after 12 h. The FSH-dependent induction of c-fos mRNA was still present in cells treated for 3 h with cycloheximide, but it was greatly reduced by actinomycin D pretreatment. These data indicate that FSH induces a transient expression of c-fos in cultured Sertoli cells. This induction is probably mediated by cAMP and likely involves an increased transcription of the c-fos gene. Early expression of this gene might be an intermediate step required for gonadotropin-dependent regulation of expression of other genes.