SERTOLI-CELL SPERMATOGENIC CELL-INTERACTION - THE INSULIN-LIKE GROWTHFACTOR-II CATION-INDEPENDENT MANNOSE 6-PHOSPHATE RECEPTOR MEDIATES CHANGES IN SPERMATOGENIC CELL GENE-EXPRESSION IN MICE

The insulin-like growth factor (IGF)-II/cation-independent mannose 6-p hosphate receptor (Cl-MPR) is a multifunctional receptor with distinct binding sites for IGF-II and mannose 6-phosphate (M6P)-bearing glycop roteins. We used the immediate-early response gene c-fos to assay earl y changes in gene expression in spermatogenic cells in response to lig ands for this receptor that are present in the seminiferous epithelium . We confirmed that c-fos behaves as an immediate-early response gene in spermatogenic cells after stimulation of protein kinase C with phor bol ester or after intercellular calcium levels are raised with calciu m ionophore. After determining that IGF-II mRNA is present in Sertoli cells, we treated spermatogenic cells with this growth factor and foun d that it increased c-fos mRNA levels in a dose-dependent manner. Simi larly, Sertoli cell-conditioned medium (SCM) caused a dose-dependent i ncrease in c-fos levels in spermatogenic cells isolated from adult mic e. This effect was inhibited in the presence of 5 mM M6P, demonstratin g that this change in c-fos gene expression was mediated by the IGF-II /Cl-MPR. In addition, SCM treatment of purified pachytene spermatocyte s and round spermatids caused a dose-dependent increase in 18S rRNA le vels that was completely abolished in the presence of M6P. Our results provide direct evidence that IGF-II/Cl-MPR ligands secreted by Sertol i cells can modulate gene expression in spermatogenic cells and strong ly suggest that they are important in the regulation of spermatogenesi s.