A role for GPRx, a novel GPR3/6/12-related G-protein coupled receptor, in the maintenance of meiotic arrest in Xenopus laevis oocytes

Progesterone-induced Xenopus laevis oocyte maturation is mediated via a plasma membrane-bound receptor and does not require gene transcription. Evidence from several species suggests that the relevant progesterone receptor is a G-protein coupled receptor (GPCR) and that a second receptor-GPR3 and/or GPR12 in mammals-tonically opposes the progesterone receptor. We have cloned a novel X. laevis GPCR, GPRx, which may play a similar role to GPR3/GPR12 in amphibians and fishes. GPRx is related to but distinct from GPR3, GPR6, and GPR12; GPRx orthologs are present in Xenopus tropicalis and Danio rerio, but apparently not in birds or mammals. X. laevis GPRx is mainly expressed in brain, ovary, and testis. The GPRx mRNA increases during oogenesis, persists during oocyte maturation and early embryogenesis, and then falls after the midblastula transition. Microinjection of GPRx mRNA increases the concentration of cAMP in oocytes and causes the oocytes to fail to respond to progesterone, and this block is reversed by co-injecting GPRx with morpholino oligonucleotides. Morpholino injections did not cause spontaneous maturation of oocytes, but did accelerate progesterone-induced maturation. Thus, GPRx contributes to the maintenance of G2-arrest in immature X. laevis oocytes.