Proestrus Differentially Regulates Expression of Ion Channel and Calcium Homeostasis Genes in GnRH Neurons of Mice

Vastagh, Csaba; Solymosi, Norbert; Farkas, Imre; Liposits, Zsolt

doi:10.3389/fnmol.2019.00137

Cited by 18 publications

(15 citation statements)

References 92 publications

(142 reference statements)

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“…The most potential neurotransmitter regulators include gammaaminobutyric acid (GABA) (Herbison and Moenter, 2011), glutamate (Iremonger et al, 2010), dopamine (DA) (Liu and Herbison, 2013), norepinephrine (NE) (Hosny and Jennes, 1998), serotonin (Bhattarai et al, 2014), acetylcholine (Ach) (Turi et al, 2008), and histamine (H) (Fekete et al, 1999). The expression of genes encoding for neurotransmitter receptors (Todman et al, 2005) and ion channels (Bosch et al, 2013;Norberg et al, 2013;Vastagh et al, 2019) in GnRH neurons has also been verified. In a recent study, we have reported that several neurotransmitter receptors belonging to the aforementioned systems show differential expression in GnRH neurons of proestrous mice (Vastagh et al, 2016).…”

Section: Introductionmentioning

confidence: 95%

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

Vastagh

Csillag

Solymosi

et al. 2021

Front. Mol. Neurosci.

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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.

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Section: Introductionmentioning

confidence: 95%

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

Vastagh

Csillag

Solymosi

et al. 2021

Front. Mol. Neurosci.

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“…T-type Ca 2+ channels (T-channels) can be activated by small depolarizations of the plasma membrane and have been implicated in a variety of physiological processes, including fertilization, neuronal firing, cancer therapy, hormone secretion and muscle fiber development [8][9][10][11][12] . Bijlenga 13 .…”

Section: Introductionmentioning

confidence: 99%

CACNA1H downregulation induces skeletal muscle atrophy involving endoplasmic reticulum stress activation and autophagy flux blockade

Hao

et al. 2020

Cell Death Dis

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Multiple vaginal delivery (MVD) is an important factor for pelvic floor muscle (PFM) function decline and pelvic floor dysfunction (PFD). PFD is common in middle-aged and elderly women, but its pathogenesis is not clear. In this study, we found that the expression of CACNA1H was lower in the PFM of old mice after MVD compared with old or adult mice. In in-vitro studies, we found that treatment with the T-type Ca 2+ channel (T-channel) inhibitor NNC-55 or downregulation of the CACNA1H gene by siRNA intervention promoted myotube atrophy and apoptosis. Mechanistically, we revealed that NNC-55 increased the expression of GRP78 and DDIT3 in myotubes, indicating endoplasmic reticulum stress (ERS) activation, and that the IRE1 and PERK pathways might be involved in this effect. NNC-55 induced the formation of autophagosomes but inhibited autophagy flux. Moreover, rapamycin, an autophagy activator, did not rescue myotube atrophy or apoptosis induced by NNC-55, and the autophagy inhibitors 3-MA and HCQ accelerated this damage. Further studies showed that the ERS inhibitors 4-PBA and TUDAC relieved NNC-55-induced damage and autophagy flux blockade. Finally, we found multisite muscle atrophy and decreased muscle function in Cacna1h −/− (TH-null) mice, as well as increased autophagy inhibition and apoptotic signals in the PFM of old WT mice after MVD and TH-null mice. Taken together, our results suggest that MVD-associated PFD is partially attributed to CACNA1H downregulation-induced PFM atrophy and that ERS is a potential therapeutic target for this disease.

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“…Moreover, Cav3.2 may have a role in reproduction since it facilitates the influx of Ca 2+ in mouse oocytes and eggs to maintain Ca 2+ homeostasis during oocyte maturation and post fertilization 38 . The murine Cacna1h gene is also upregulated in the proestrus of the Gonadotropin-releasing hormone (GnRH) neurons 39 . GnRH determines the pattern of secretion of follicle stimulating hormone (FSH) and luteinising hormone (LH) that regulate the endocrine function and gamete maturation of gonads 40 .…”

Section: Discussionmentioning

confidence: 99%

Detection of loci exhibiting pleiotropic effects on body weight and egg number in female broilers

Tarsani

Kranis

Maniatis

et al. 2021

Sci Rep

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The objective of the present study was to discover the genetic variants, functional candidate genes, biological processes and molecular functions underlying the negative genetic correlation observed between body weight (BW) and egg number (EN) traits in female broilers. To this end, first a bivariate genome-wide association and second stepwise conditional-joint analyses were performed using 2586 female broilers and 240 k autosomal SNPs. The aforementioned analyses resulted in a total number of 49 independent cross-phenotype (CP) significant SNPs with 35 independent markers showing antagonistic action i.e., positive effects on one trait and negative effects on the other trait. A number of 33 independent CP SNPs were located within 26 and 14 protein coding and long non-coding RNA genes, respectively. Furthermore, 26 independent markers were situated within 44 reported QTLs, most of them related to growth traits. Investigation of the functional role of protein coding genes via pathway and gene ontology analyses highlighted four candidates (CPEB3, ACVR1, MAST2 and CACNA1H) as most plausible pleiotropic genes for the traits under study. Three candidates (CPEB3, MAST2 and CACNA1H) were associated with antagonistic pleiotropy, while ACVR1 with synergistic pleiotropic action. Current results provide a novel insight into the biological mechanism of the genetic trade-off between growth and reproduction, in broilers.

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Proestrus Differentially Regulates Expression of Ion Channel and Calcium Homeostasis Genes in GnRH Neurons of Mice

Cited by 18 publications

References 92 publications

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

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

CACNA1H downregulation induces skeletal muscle atrophy involving endoplasmic reticulum stress activation and autophagy flux blockade

Detection of loci exhibiting pleiotropic effects on body weight and egg number in female broilers

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