Effect of the gonadotropin-releasing hormone antagonist ganirelix on cyclic adenosine monophosphate accumulation of human granulosa-lutein cells

Objective: To evaluate whether the GnRH antagonist ganirelix exerts an effe ct on cyclic adenosine monophosphate (cAMP) production of human granulosa-l utein (GL) cells in vitro. Design: In vitro cell culture study. Setting: Research laboratory of a university hospital. Patient(s): Mural GL and cumulus cells were obtained from 15 patients on wh om controlled ovarian hyperstimulation was being performed for intracytopla smic sperm injection treatment. Intervention(s): Mural CL and cumulus cells were cultured for 48 hours with and without 1 nM ganirelix or triptorelin. For the last 6 hours, the cells were either exposed to 1-5 IU hCG or left unstimulated. Main Outcome Measure(s): At the end of the culturing period, the intracellu lar and extracellular cAMP accumulations were measured by an I-125-scintill ation proximity assay. Result(s): hCG induced dose-dependent increases in total cAMP accumulation. Stimulation with 1 IU/mL hCG resulted in 9-fold and 13-fold increases, and 5 IU/mL hCG resulted in 19-fold and 14-fold increases in total cAMP releas e from cumulus and mural GL cells, respectively. On the other hand, treatme nts with 1 nM GnRH antagonist ganirelix and 1 nM GnRH agonist triptorelin d id not exert any significant changes on the basal and hCG-stimulated cAMP a ccumulation of mural GL cells and cumulus cells as compared with controls. Conclusion(s): Ganirelix does not influence basal and hCG-stimulated cAMP a ccumulation of human GL cells in vitro, cAMP is apparently not involved in the mechanism of action of GnRH analogs in human ovary. (C) 2000 by America n Society for Reproductive Medicine.