Multiple G proteins compete for binding with the human gonadotropin releasing hormone receptor

The GnRH receptor is coupled to G proteins of the families Gq and G11. Gq and G11 coupling leads to intracellular signaling through the phospholipase C pathway. GnRHR coupling to other G proteins is controversial. This study provides evidence that G protein families Gs, Gi, Gq and G11 complete for binding with the GnRHR. We quantified interactions of over-expressed G proteins with GnRHR by a competitive binding approach, using measurements of second messengers, IP and cAMP. Transient co-transfection of HEK293 cells with human WT GnRHR and with stimulatory and inhibitory G proteins (Gq, G11 and Gs, Gi) led to either production or inhibition of total inositol phosphate (IP) production, depending on the G protein that was over-expressed. Studies were conducted in different human (COS7, HeLa) and rodent-derived (CHO-K1, GH3) cell lines in order to confirm that G protein promiscuity observed with the GnRHR was not limited to a particular cell type.