Activation of protein kinase C increases proteoglycan synthesis in immature rat Sertoli cells

In order to determine the signal transduction pathways involved in the regu lation of proteoglycan (PG) synthesis in immature rat Sertoli cells (SC), w e have examined the effect of the tumor promoter phorbol ester PMA (phorbol myristate acetate) on [S-35]sulfate and [H-3]glucosamine incorporation int o PG molecules neosynthesized by cultured rat SC. PMA induced a dose- and t ime-dependent stimulation of labeled cell-associated PG as determined by qu antitative solid phase assay. The overall effect of PMA resulted from enhan cement of both glycosylation and catabolism of cell PG, this latter effect leading to a drastic decrease of their residence time in the membrane. Besi des these quantitative effects, activation of protein kinase C by PMA induc ed qualitative changes as reflected by increase in relative proportion of h eparan sulfate PG (HSPG) in cell membrane PG. In light of our previous resu lts suggesting an inverse relationship between PG synthesis and FSH respons iveness in immature rat Sertoli cells, the PMA-induced upregulation of cell membrane PG, and particularly HSPG, could constitute one mechanism involve d in the repression of FSH-stimulated steroidogenesis induced by PKC activa tion. (C) 1999 Elsevier Science B.V. All rights reserved.