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 hCG release after 3 h incubation in a dose-dependent manner with ED50 of 55 nmol/l and 4.0 nmol/l, respectively. A tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) also stimulated hCG release while two non-tumor-promoting compounds, phorbol and 4 alpha-phorbol, failed to stimulate hCG release. hCG release by maximal effective dose of GnRH (10 mumol/l) or OAG (1 mumol/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.
Iwashita
M
M
Maternal and Perinatal Center, Tokyo, Japan.
Watanabe
M
M
Setoyama
T
T
Mimuro
T
T
Nakayama
S
S
Adachi
T
T
Takeda
Y
Y
Sakamoto
S
S
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism
D006063:Chorionic Gonadotropin; D004075:Diglycerides; D007546:Isoquinolines; D010879:Piperazines; D007987:Gonadotropin-Releasing Hormone; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate