KEGG   PATHWAY: bbub04929
Entry
bbub04929                   Pathway                                
Name
GnRH secretion - Bubalus bubalis (water buffalo)
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
bbub04929  GnRH secretion
bbub04929

Organism
Bubalus bubalis (water buffalo) [GN:bbub]
Gene
102393947  KISS1; metastasis-suppressor KiSS-1 [KO:K23140]
102399302  KISS1R; kiSS-1 receptor [KO:K08374]
102409250  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102391819  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
102412320  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
102405830  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
102413748  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
102389945  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
102415611  PRKCA; protein kinase C alpha type isoform X4 [KO:K02677] [EC:2.7.11.13]
102407189  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
102397646  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
102412452  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X8 [KO:K04958]
102401062  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
102409793  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
102409013  HCN1; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 [KO:K04954]
102390284  HCN2; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 [KO:K04955]
102393285  HCN3; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X3 [KO:K04956]
102396837  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X2 [KO:K04854]
102415705  CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H isoform X4 [KO:K04855]
102411380  TRPC1; short transient receptor potential channel 1 isoform X4 [KO:K04964]
102407365  TRPC4; short transient receptor potential channel 4 [KO:K04967]
102404657  KCNJ11; ATP-sensitive inward rectifier potassium channel 11 [KO:K05004]
102410731  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
102400825  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
102402372  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
102392060  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
102399037  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X1 [KO:K04615]
102393080  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X3 [KO:K04615]
102402582  KCNN1; small conductance calcium-activated potassium channel protein 1 isoform X1 [KO:K04942]
102390288  KCNN2; small conductance calcium-activated potassium channel protein 2 isoform X2 [KO:K04943]
102413053  KCNN3; small conductance calcium-activated potassium channel protein 3 isoform X2 [KO:K04944]
102412110  KCNN4; intermediate conductance calcium-activated potassium channel protein 4 [KO:K04945]
102397191  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
102407190  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X9 [KO:K04850]
102405249  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
102407399  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
102398812  ARRB2; beta-arrestin-2 isoform X3 [KO:K04439]
102408724  ARRB1; beta-arrestin-1 isoform X4 [KO:K04439]
112587129  GTPase HRas-like [KO:K02833]
102392995  KRAS; GTPase KRas isoform X2 [KO:K07827]
102399487  NRAS; GTPase NRas isoform X2 [KO:K07828]
102412922  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102396842  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102401744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
102396206  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
102403296  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102415109  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102404517  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
102395384  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
102404165  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102400519  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102404610  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102397969  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102398761  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102391021  AKT3; RAC-gamma serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
102408995  progonadoliberin-2 [KO:K05252]
102393270  GNRH1; progonadoliberin-1 isoform X1 [KO:K05252]
102390058  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
102391241  LHB; luteinizing hormone beta polypeptide isoform X1 [KO:K08521]
102403043  SPP1; osteopontin [KO:K06250]
123464610  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
bbub04010  MAPK signaling pathway
bbub04020  Calcium signaling pathway
bbub04151  PI3K-Akt signaling pathway
bbub04912  GnRH signaling pathway
bbub04913  Ovarian steroidogenesis
bbub04915  Estrogen signaling pathway
KO pathway
ko04929   
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