KEGG   PATHWAY: mmyo04929
Entry
mmyo04929                   Pathway                                
Name
GnRH secretion - Myotis myotis (greater mouse-eared bat)
Description
Hypothalamic gonadotropin-releasing hormone (GnRH) neurons are key regulators of reproduction. They release GnRH into the portal circulation. In turn, GnRH stimulates the pituitary gland to secrete follicle-stimulating hormone and luteinizing hormone (LH) to regulate gonadal functions. Gonadal steroids provide feedback to regulate GnRH release. GnRH neurons express the kisspeptin receptor, GPR 54, and kisspeptins potently stimulate the release of GnRH by depolarising and inducing sustained action potential firing in GnRH neurons. It is also demonstrated that Kisspeptin-GPR54 system positively regulates the GnRH expression  with a time course consistent with activation of Akt and MAP kinase signaling pathways.
Class
Organismal Systems; Endocrine system
Pathway map
mmyo04929  GnRH secretion
mmyo04929

Organism
Myotis myotis (greater mouse-eared bat) [GN:mmyo]
Gene
118672942  KISS1; LOW QUALITY PROTEIN: metastasis-suppressor KiSS-1 [KO:K23140]
118659157  KISS1R; LOW QUALITY PROTEIN: kiSS-1 receptor [KO:K08374]
118667437  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
118658361  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
118649794  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
118663015  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
118663147  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
118665361  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
118671569  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
118655815  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
118660957  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
118668410  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
118652119  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
118679657  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
118657055  HCN1; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 [KO:K04954]
118658358  HCN2; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 [KO:K04955]
118673207  HCN3; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 [KO:K04956]
118671751  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
118652918  CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H isoform X1 [KO:K04855]
118651799  CACNA1I; voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856]
118676003  TRPC1; short transient receptor potential channel 1 isoform X1 [KO:K04964]
118650517  TRPC4; short transient receptor potential channel 4 [KO:K04967]
118654619  TRPC5; short transient receptor potential channel 5 [KO:K04968]
118664885  KCNJ11; ATP-sensitive inward rectifier potassium channel 11 [KO:K05004]
118662127  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
118675034  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
118673633  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
118678506  KCNJ5; G protein-activated inward rectifier potassium channel 4 isoform X1 [KO:K04999]
118667267  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
118659648  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
118658071  KCNN1; small conductance calcium-activated potassium channel protein 1 isoform X1 [KO:K04942]
118656781  KCNN2; small conductance calcium-activated potassium channel protein 2 isoform X1 [KO:K04943]
118673419  KCNN3; small conductance calcium-activated potassium channel protein 3 isoform X1 [KO:K04944]
118674466  KCNN4; intermediate conductance calcium-activated potassium channel protein 4 isoform X1 [KO:K04945]
118678862  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
118652154  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
118667975  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
118654729  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
118671946  ARRB2; beta-arrestin-2 isoform X1 [KO:K04439]
118664634  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
118648965  HRAS; GTPase HRas isoform X1 [KO:K02833]
118649554  KRAS; GTPase KRas isoform X1 [KO:K07827]
118672986  NRAS; GTPase NRas [KO:K07828]
118668076  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
118654213  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
118657986  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
118678650  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
118656605  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
118675217  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
118656203  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
118657573  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
118677590  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118668125  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118675045  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118678909  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118655031  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118674834  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118658895  GNRH1; progonadoliberin-1 [KO:K05252]
118662459  LOW QUALITY PROTEIN: progonadoliberin-2 [KO:K05252]
118664766  ESR2; estrogen receptor beta [KO:K08551]
118659230  GPER1; G-protein coupled estrogen receptor 1 [KO:K04246]
118655448  lutropin subunit beta [KO:K08521]
118671281  SPP1; osteopontin [KO:K06250]
118660297  CGA; glycoprotein hormones alpha chain [KO:K08522]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00238  Potassium cation
C00334  4-Aminobutanoate
C00535  Testosterone
C00951  Estradiol-17beta
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C04637  1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
Reference
PMID:23550004
  Authors
Ronnekleiv OK, Kelly MJ
  Title
Kisspeptin excitation of GnRH neurons.
  Journal
Adv Exp Med Biol 784:113-31 (2013)
DOI:10.1007/978-1-4614-6199-9_6
Reference
PMID:24145132
  Authors
Beltramo M, Dardente H, Cayla X, Caraty A
  Title
Cellular mechanisms and integrative timing of neuroendocrine control of GnRH secretion by kisspeptin.
  Journal
Mol Cell Endocrinol 382:387-399 (2014)
DOI:10.1016/j.mce.2013.10.015
Reference
PMID:19770291
  Authors
Oakley AE, Clifton DK, Steiner RA
  Title
Kisspeptin signaling in the brain.
  Journal
Endocr Rev 30:713-43 (2009)
DOI:10.1210/er.2009-0005
Reference
PMID:22811428
  Authors
Pinilla L, Aguilar E, Dieguez C, Millar RP, Tena-Sempere M
  Title
Kisspeptins and reproduction: physiological roles and regulatory mechanisms.
  Journal
Physiol Rev 92:1235-316 (2012)
DOI:10.1152/physrev.00037.2010
Reference
PMID:20699467
  Authors
d'Anglemont de Tassigny X, Colledge WH
  Title
The role of kisspeptin signaling in reproduction.
  Journal
Physiology (Bethesda) 25:207-17 (2010)
DOI:10.1152/physiol.00009.2010
Reference
PMID:19464345
  Authors
Tena-Sempere M
  Title
Kisspeptin signaling in the brain: recent developments and future challenges.
  Journal
Mol Cell Endocrinol 314:164-9 (2010)
DOI:10.1016/j.mce.2009.05.004
Reference
PMID:19097915
  Authors
Colledge WH
  Title
Kisspeptins and GnRH neuronal signalling.
  Journal
Trends Endocrinol Metab 20:115-21 (2009)
DOI:10.1016/j.tem.2008.10.005
Reference
PMID:18793689
  Authors
Roa J, Castellano JM, Navarro VM, Handelsman DJ, Pinilla L, Tena-Sempere M
  Title
Kisspeptins and the control of gonadotropin secretion in male and female rodents.
  Journal
Peptides 30:57-66 (2009)
DOI:10.1016/j.peptides.2008.08.009
Reference
PMID:24907402
  Authors
Piet R, de Croft S, Liu X, Herbison AE
  Title
Electrical properties of kisspeptin neurons and their regulation of GnRH neurons.
  Journal
Front Neuroendocrinol 36:15-27 (2015)
DOI:10.1016/j.yfrne.2014.05.006
Reference
PMID:23744639
  Authors
Zhang C, Bosch MA, Ronnekleiv OK, Kelly MJ
  Title
Kisspeptin activation of TRPC4 channels in female GnRH neurons requires PIP2 depletion and cSrc kinase activation.
  Journal
Endocrinology 154:2772-83 (2013)
DOI:10.1210/en.2013-1180
Reference
PMID:20816765
  Authors
Ronnekleiv OK, Bosch MA, Zhang C
  Title
Regulation of endogenous conductances in GnRH neurons by estrogens.
  Journal
Brain Res 1364:25-34 (2010)
DOI:10.1016/j.brainres.2010.08.096
Reference
PMID:25612870
  Authors
Ronnekleiv OK, Zhang C, Bosch MA, Kelly MJ
  Title
Kisspeptin and Gonadotropin-Releasing Hormone Neuronal Excitability: Molecular Mechanisms Driven by 17beta-Estradiol.
  Journal
Neuroendocrinology 102:184-93 (2015)
DOI:10.1159/000370311
Reference
PMID:22343183
  Authors
Zhang XB, Spergel DJ
  Title
Kisspeptin inhibits high-voltage activated Ca2+ channels in GnRH neurons via multiple Ca2+ influx and release pathways.
  Journal
Neuroendocrinology 96:68-80 (2012)
DOI:10.1159/000335985
Reference
PMID:19576263
  Authors
Novaira HJ, Ng Y, Wolfe A, Radovick S
  Title
Kisspeptin increases GnRH mRNA expression and secretion in GnRH secreting neuronal cell lines.
  Journal
Mol Cell Endocrinol 311:126-34 (2009)
DOI:10.1016/j.mce.2009.06.011
Reference
PMID:25314270
  Authors
Glanowska KM, Moenter SM
  Title
Differential regulation of GnRH secretion in the preoptic area (POA) and the median eminence (ME) in male mice.
  Journal
Endocrinology 156:231-41 (2015)
DOI:10.1210/en.2014-1458
Reference
PMID:20886089
  Authors
Szereszewski JM, Pampillo M, Ahow MR, Offermanns S, Bhattacharya M, Babwah AV
  Title
GPR54 regulates ERK1/2 activity and hypothalamic gene expression in a Galpha(q/11) and beta-arrestin-dependent manner.
  Journal
PLoS One 5:e12964 (2010)
DOI:10.1371/journal.pone.0012964
Reference
PMID:19710308
  Authors
Zhang C, Bosch MA, Rick EA, Kelly MJ, Ronnekleiv OK
  Title
17Beta-estradiol regulation of T-type calcium channels in gonadotropin-releasing hormone neurons.
  Journal
J Neurosci 29:10552-62 (2009)
DOI:10.1523/JNEUROSCI.2962-09.2009
Reference
PMID:23880664
  Authors
Terasaka T, Otsuka F, Tsukamoto N, Nakamura E, Inagaki K, Toma K, Ogura-Ochi K, Glidewell-Kenney C, Lawson MA, Makino H
  Title
Mutual interaction of kisspeptin, estrogen and bone morphogenetic protein-4 activity in GnRH regulation by GT1-7 cells.
  Journal
Mol Cell Endocrinol 381:8-15 (2013)
DOI:10.1016/j.mce.2013.07.009
Reference
PMID:22654870
  Authors
Radovick S, Levine JE, Wolfe A
  Title
Estrogenic regulation of the GnRH neuron.
  Journal
Front Endocrinol (Lausanne) 3:52 (2012)
DOI:10.3389/fendo.2012.00052
Reference
PMID:16373418
  Authors
Dungan HM, Clifton DK, Steiner RA
  Title
Minireview: kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion.
  Journal
Endocrinology 147:1154-8 (2006)
DOI:10.1210/en.2005-1282
Reference
PMID:16627563
  Authors
Kato M, Tanaka N, Usui S, Sakuma Y
  Title
The SK channel blocker apamin inhibits slow afterhyperpolarization currents in rat gonadotropin-releasing hormone neurones.
  Journal
J Physiol 574:431-42 (2006)
DOI:10.1113/jphysiol.2006.110155
Reference
PMID:23548613
  Authors
Zhang C, Ronnekleiv OK, Kelly MJ
  Title
Kisspeptin inhibits a slow afterhyperpolarization current via protein kinase C and reduces spike frequency adaptation in GnRH neurons.
  Journal
Am J Physiol Endocrinol Metab 304:E1237-44 (2013)
DOI:10.1152/ajpendo.00058.2013
Related
pathway
mmyo04010  MAPK signaling pathway
mmyo04020  Calcium signaling pathway
mmyo04151  PI3K-Akt signaling pathway
mmyo04912  GnRH signaling pathway
mmyo04913  Ovarian steroidogenesis
mmyo04915  Estrogen signaling pathway
KO pathway
ko04929   
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