Gonadal Cycle-Dependent Expression of Genes Encoding Peptide-, Growth Factor-, and Orphan G-Protein-Coupled Receptors in Gonadotropin- Releasing Hormone Neurons of Mice

Rising serum estradiol triggers the surge release of gonadotropin-releasing hormone (GnRH) at late proestrus leading to ovulation. We hypothesized that evokes alterations in peptidergic signaling onto GnRH neurons inducing a differential expression neuropeptide-, growth factor-, and orphan G-protein-coupled receptor (GPCR) genes. Thus, we analyzed transcriptome collected from intact, proestrous metestrous GnRH-green fluorescent protein (GnRH-GFP) transgenic mice using Affymetrix microarray technique. Proestrus resulted genes coding for peptide/neuropeptide receptors including Adipor1, Prokr1, Ednrb, Rtn4r, Nmbr, Acvr2b, Sctr, Npr3, Nmur1, Mc3r, Cckbr , Amhr2 . In this gene cluster, Adipor1 mRNA was upregulated others were downregulated. Expression factor their related proteins also altered showing upregulation Fgfr1, Igf1r, Grb2, Grb10 Ngfrap1 downregulation Egfr Tgfbr2 Gpr107 an GPCR, during proestrus, while significantly downregulated ( Gpr1, Gpr87, Gpr18, Gpr62, Gpr125, Gpr183, Gpr4 Gpr88 ). Further affected included vomeronasal Vmn1r172, Vmn2r-ps54 Vmn1r148 ) platelet-activating Ptafr ), all with marked downregulation. Patch-clamp recordings mouse GnRH-GFP carried out metestrus confirmed differentially expressed IGF-1, secretin, GPR107 operational, as activation by specific ligands evoked increase frequency miniature postsynaptic currents (mPSCs). These findings show contribution certain novel peptides, factors, GPCRs regulation preparation release.