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

血清雌二醇水平升高会触发发情后期晚期促性腺激素释放激素（GnRH）的大量释放，从而导致排卵。我们假设发情期引起了GnRH神经元上的肽能信号的改变，从而诱导了神经肽，生长因子和孤儿G蛋白偶联受体（GPCR）基因的差异表达。因此，我们使用Affymetrix微阵列技术分析了从完整，前发和肠胃的GnRH-绿色荧光蛋白（GnRH-GFP）转基因小鼠中收集的GnRH神经元的转录组。发情期导致编码肽/神经肽受体的基因的差异表达，包括Adipor1，Prokr1，Ednrb，Rtn4r，Nmbr，Acvr2b，Sctr，Npr3，Nmur1，Mc3r，Cckbr和 Amhr2。在这个基因簇中Adipor1mRNA表达上调，其他mRNA下调。生长因子受体及其相关蛋白的表达也被改变，显示出上调Fgfr1，Igf1r，Grb2，Grb10和 Ngfrap1 和下调 埃格弗 和 Tgfbr2 基因。 Gpr107，一个孤儿GPCR，在发情期间被上调，而其他人则被显着下调（Gpr1，Gpr87，Gpr18，Gpr62，Gpr125，Gpr183，Gpr4和 Gpr88）。进一步受影响的受体包括犁鼻受体（Vmn1r172，Vmn2r-ps54和 Vmn1r148）和血小板活化因子受体（聚四氟乙烯），所有这些都有明显的下调。在小鼠腹部进行的小鼠GnRH-GFP神经元的膜片钳记录证实，差异表达的IGF-1，促胰液素和GPR107受体是有效的，因为它们被特定配体激活引起微型突触后电流（mPSC）频率增加。 。这些发现表明，某些新颖的肽，生长因子和孤儿GPCR的配体对GnRH神经元的调节及其为电涌释放所做的准备。