NF-kappa B induces cAMP-response element-binding protein gene transcription in Sertoli cells

Spermatogenesis is dependent upon Sertoli cells, which relay hormonal signa ls and provide factors required for the differentiation and proliferation o f germ cells. NF-kappa B transcription factors are constitutively expressed in the nuclei of Sertoli cells in rodent testis. Electrophoretic mobility shift assays demonstrated that Sertoli NF-kappa B proteins specifically bin d to kappa B enhancer motifs within the promoter of the cAMP-response eleme nt-binding protein (CREB) gene, an important mediator of hormonal signals t hat control spermatogenesis. Overexpression of NF-kappa B proteins in prima ry Sertoli and NIH 3T3 fibroblast cells induced the CREB promoter in transi ent transfection assays. Stimulation of Sertoli cells with tumor necrosis f actor-alpha, an NF-kappa B-activating cytokine produced by round spermatids located adjacent to Sertoli cells, stimulated the elimination of I kappa B , the translocation of additional NF-kappa B to the nucleus, and increased NF-kappa B binding to CREB promoter kappa B enhancer elements. Tumor necros is factor-alpha also stimulated transcription from the CREB promoter. These data demonstrate that NF-kappa B contributes to the up-regulation of CREB expression in Sertoli cells and raises the possibility that MF-kappa B may induce other Sertoli genes required for spermatogenesis. Furthermore, the C REB promoter is also inducible by NF-kappa B in MH 3T3 cells suggesting tha t NF-kappa B may be a general regulator of CREB in non-testis tissues.