LIVER-REGULATING PROTEIN (LRP) IS A PLASMA-MEMBRANE PROTEIN INVOLVED IN CELL CONTACT-MEDIATED REGULATION OF SERTOLI-CELL FUNCTION BY PRIMARY SPERMATOCYTES

We have identified a liver-regulating protein involved in cell contact -mediated regulation of Sertoli cell function by primary spermatocytes in rat testis, Liver-regulating protein was studied using monoclonal antibody L8 prepared from rat primitive biliary epithelial cells, This molecule was located in vivo at the interface of Sertoli cells and sp ermatocytes, and expressed in a stage-dependent manner (expression pea ked on leptotene-zygotene spermatocytes), In vitro, the liver-regulati ng protein was found on Sertoli cell, spermatocyte and early spermatid membranes, Immunoaffinity procedures revealed two peptides of 85 and 73 kDa for Sertoli cells, while spermatocytes and spermatids displayed a single smaller peptide of 56 kDa, The involvement of the liver-regu lating protein in cell interaction-mediated regulation of Sertoli cell was assessed in vitro by tracing Sertoli cell transferrin and inhibin secretion, as well as mRNA synthesis in spermatocyte-Sertoli cell coc ultures and in rat liver biliary epithelial cell-Sertoli cell cocultur es, performed in the presence or absence of monoclonal antibody L8. In hibition of the spermatocyte- and liver biliary epithelial cell-stimul ated secretion of transferrin and inhibin by Sertoli cells was observe d in the presence of antibody, whereas spermatocyte adhesiveness was u nchanged, Using northern blot analysis, the steady state levels of tra nsferrin mRNA decreased when the anti-liver-regulating protein antibod y was added to the Sertoli cell-spermatocyte cocultures or to the Sert oli cell-liver biliary epithelial cell cocultures, The data demonstrat e the role of the liver-regulating protein in cell-cell contact-mediat ed regulation of Sertoli function by primary spermatocytes and the imp ortant implications of this cell contact-dependent control in testicul ar activity.