Sertoli cell-spermatogenic cell interaction: the insulin-like growth factor-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-phosphate receptor (CI-MPR) is a multifunctional receptor with distinct binding sites for IGF-II and mannose 6-phosphate (M6P)-bearing glycoproteins. We used the immediate-early response gene c-fos to assay early changes in gene expression in spermatogenic cells in response to ligands 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 phorbol ester or after intercellular calcium levels are raised with calcium ionophore. After determining that IGF-II mRNA is present in Sertoli cells, we treated spermatogenic cells with this growth factor and found that it increased c-fos mRNA levels in a dose-dependent manner. Similarly, Sertoli cell-conditioned medium (SCM) caused a dose-dependent increase in c-fos levels in spermatogenic cells isolated from adult mice. This effect was inhibited in the presence of 5 mM M6P, demonstrating that this change in c-fos gene expression was mediated by the IGF-II/Cl-MPR. In addition, SCM treatment of purified pachytene spermatocytes and round spermatids caused a dose-dependent increase in 18S rRNA levels that was completely abolished in the presence of M6P. Our results provide direct evidence that IGF-II/Cl-MPR ligands secreted by Sertoli cells can modulate gene expression in spermatogenic cells and strongly suggest that they are important in the regulation of spermatogenesis.
Tsuruta
J K
JK
Department of Pediatrics, University of North Carolina, Chapel Hill 27599-7500, USA. jtsuruta@med.unc.edu
O'Brien
D A
DA
D000818:Animals; D001483:Base Sequence; D002412:Cations; D002469:Cell Separation; D002478:Cells, Cultured; D015870:Gene Expression; D016762:Genes, fos; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D017527:Receptor, IGF Type 2 / Q000502:physiology*; D012708:Sertoli Cells / Q000166:cytology*; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism*
D002412:Cations; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D017527:Receptor, IGF Type 2; D011493:Protein Kinase C; D012194:RNA-Directed DNA Polymerase