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.
Anderson
L
L
MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, UK.
McGregor
A
A
Cook
J V
JV
Chilvers
E
E
Eidne
K A
KA
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004361:Drug Tolerance; D004622:Embryo, Mammalian; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007295:Inositol Phosphates / Q000096:biosynthesis; D007668:Kidney; D051381:Rats; D011966:Receptors, LHRH / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection
D007295:Inositol Phosphates; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium