Rapid desensitization of GnRH-stimulated intracellular signalling events in alpha T3-1 and HEK-293 cells expressing the GnRH receptor.

The gonadotropin-releasing hormone receptor (GnRH-R) desensitizes following chronic exposure to GnRH or its agonists. However, it is not certain whether the GnRH-R undergoes rapid homologous desensitization analogous to other members of the G-protein coupled receptor (GPCR) superfamily. This study investigated rapid desensitization events in two cell lines expressing the GnRH-R; (the pituitary gonadotrope alpha T3-1 cell line and the stably transfected human embryonal kidney cells, HEK-293). In both cell types, total inositol phosphate (IP) production did not desensitize, increasing linearly over 10 min. Short-term GnRH pretreatment also did not desensitize the rapid phase ( < or = sec) of the early Ins1,4,5P3 response despite a partial desensitization of the plateau phase ( > 1 min). It is likely that Ins1,4,5P3 metabolism rather than desensitization is responsible for this partial effect. In contrast, GnRH-stimulated calcium responses did desensitize in a dose-dependent fashion in both alpha T3-1 and HEK 293 cells expressing the GnRH-R. These results suggest that rapid GnRH-R desensitization occurs at a level beyond both the receptor and phospholipase C (PLC) activation. These events were receptor specific and not related to cell type, since similar rapid desensitization profiles were observed in both GnRH-R expressing pituitary and nonpituitary cell types. In contrast, profiles of GnRH-stimulated calcium responses were cell type specific.