KEGG   PATHWAY: pps04929
Entry
pps04929                    Pathway                                
Name
GnRH secretion - Pan paniscus (bonobo)
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
pps04929  GnRH secretion
pps04929

Organism
Pan paniscus (bonobo) [GN:pps]
Gene
112436700  KISS1; metastasis-suppressor KiSS-1 [KO:K23140]
100967874  KISS1R; kiSS-1 receptor [KO:K08374]
100986730  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
100972605  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
100969660  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
100987524  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
100969344  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X4 [KO:K05858] [EC:3.1.4.11]
100978643  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100967981  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100970296  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
100990245  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100984884  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
100980378  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
100982024  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X6 [KO:K04960]
100994699  HCN1; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 [KO:K04954]
100989417  LOW QUALITY PROTEIN: potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2-like [KO:K04955]
100981425  HCN3; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X1 [KO:K04956]
100983419  voltage-dependent T-type calcium channel subunit alpha-1G isoform X6 [KO:K04854]
100983134  CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H isoform X8 [KO:K04855]
100972510  CACNA1I; voltage-dependent T-type calcium channel subunit alpha-1I isoform X1 [KO:K04856]
100973473  TRPC1; short transient receptor potential channel 1 isoform X4 [KO:K04964]
100989868  TRPC4; short transient receptor potential channel 4 isoform X2 [KO:K04967]
100991195  TRPC5; short transient receptor potential channel 5 [KO:K04968]
100980303  KCNJ11; ATP-sensitive inward rectifier potassium channel 11 isoform X1 [KO:K05004]
100972367  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
100975815  KCNJ6; G protein-activated inward rectifier potassium channel 2 isoform X1 [KO:K05000]
100969260  KCNJ9; G protein-activated inward rectifier potassium channel 3 isoform X1 [KO:K05002]
100969758  KCNJ5; G protein-activated inward rectifier potassium channel 4 isoform X1 [KO:K04999]
100983001  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X1 [KO:K04615]
100974195  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X2 [KO:K04615]
100971347  KCNN1; small conductance calcium-activated potassium channel protein 1 isoform X4 [KO:K04942]
100989539  KCNN2; small conductance calcium-activated potassium channel protein 2 isoform X1 [KO:K04943]
100971008  KCNN3; small conductance calcium-activated potassium channel protein 3 isoform X1 [KO:K04944]
100979144  KCNN4; intermediate conductance calcium-activated potassium channel protein 4 isoform X1 [KO:K04945]
100982136  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
100971701  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
100975108  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X3 [KO:K04851]
100988624  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
100988967  ARRB2; beta-arrestin-2 isoform X2 [KO:K04439]
100984768  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
100993386  HRAS; GTPase HRas isoform X1 [KO:K02833]
100990801  KRAS; GTPase KRas isoform X1 [KO:K07827]
100970465  NRAS; GTPase NRas isoform X2 [KO:K07828]
100972902  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100988422  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100977025  dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
100988437  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
100979542  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
100995567  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100994315  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100986080  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
100969981  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100989732  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100990828  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100990108  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100969444  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100991804  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100969217  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100992576  GNRH1; progonadoliberin-1 isoform X1 [KO:K05252]
100988122  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
100967334  G-protein coupled estrogen receptor 1 [KO:K04246]
117974319  LOW QUALITY PROTEIN: G-protein coupled estrogen receptor 1-like [KO:K04246]
100994106  SPP1; osteopontin isoform X1 [KO:K06250]
103786698  osteopontin [KO:K06250]
100987945  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
pps04010  MAPK signaling pathway
pps04020  Calcium signaling pathway
pps04151  PI3K-Akt signaling pathway
pps04912  GnRH signaling pathway
pps04913  Ovarian steroidogenesis
pps04915  Estrogen signaling pathway
KO pathway
ko04929   
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