EFFECTS OF DIACYLGLYCEROL AND GONADOTROPIN-RELEASING-HORMONE ON HUMAN CHORIONIC-GONADOTROPIN RELEASE BY CULTURED TROPHOBLAST CELLS

The effect of activation of calcium- and phospholipid-dependent protein kinase (protein kinase C) on human chorionic gonadotropin (hCG) release by cultured trophoblast cells was studied and a role of protein kinase C in the GnRH-mediated hCG release was also evaluated. Both GnRH and 1-oleoyl-2- acetylglycerol (OAG), a protein kinase C activator, stimulated h CG release after 3 h incubation in a dosedependent manner with ED50 of 55 nmol/l and 4.0 nmol/l, respectively. A tumor-promoting phorbol ester, 12-0-tetradecanoylphorbol-13-acetate (TPA) also stimulated hCG release while two non-tumor-promoting compounds, phorbol and 4α-phorbol, failed to stimulate hCG release. hCG release by maximal effective dose of GnRH (10 μmol/l or OAG (1 μmol/l) was further stimulated when cells were incubated with same concentrations of GnRH and OAG. OAG-stimulated hCG release was completely inhibited by a protein kinase C inhibitor, H-7, with ID50 of 23 nmol/l while H-7 did not affect GnRH-mediated hCG release. These results indicate that GnRH-stimulated hCG release is not mediated by protein kinase C pathway, however, the secretion of hCG is also regulated by the mechanism that involves protein kinase C activation. © 1992.