GONADOTROPIN-RELEASING-HORMONE STIMULATES PHOSPHOLIPASE-C BUT NOT PROTEIN-PHOSPHORYLATION DEPHOSPHORYLATION IN PLASMA-MEMBRANE FROM HUMAN EPITHELIAL OVARIAN-CANCER

In view of advances in treatment of certain hormone-dependent cancers with analogues of gonadotropin-releasing hormone (Gn-RH), this study was undertaken to establish the signal transduction events interacting with Gn-RH receptor in a cell-free system prepared from human ovarian mucinous cystadenocarcinoma samples. A high affinity specific binding (K(d) = 8 x 10(-9) M) of [H-3]Gn-RH was demonstrated in two from two plasma membrane preparations. Gn-RH showed no effects on the rate of protein phosphorylation from [gamma-P-32] adenosine triphosphate in the plasma membrane preparations. On the other hand, incubation of plasma membrane isolated form [H-3]inositol-labeled specimens with Gn-RH in the presence of guanosine thiotriphosphate resulted in the rapid production of inositol phosphates. The Gn-RH effects was concentration-dependent, and half-maximal activation occurred with 1-3 nm Gn-RH. The Gn-RH-stimulated membrane event was observed in all plasma membrane isolations tested, but not in those from uterine endometrial carcinoma of a given case. These results provide the first direct evidence that Gn-RH receptor is coupled to phosphoinositide hydrolysis but not to certain membrane protein phosphorylation/dephosphorylation in ovarian carcinoma plasma membrane. Though the functional role of this event in human ovarian cancer is still obscure, it might be part of a possible point of attack for therapeutic approaches using Gn-RH analogues in this malignancy.