KEGG   PATHWAY: ocu04929
Entry
ocu04929                    Pathway                                
Name
GnRH secretion - Oryctolagus cuniculus (rabbit)
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
ocu04929  GnRH secretion
ocu04929

Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100008648  KCNJ11; ATP-sensitive inward rectifier potassium channel 11 [KO:K05004]
100008730  [KO:K04956]
100008732  HCN1; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 [KO:K04954]
100008865  [KO:K05000]
100008939  [KO:K04960]
100008982  SPP1; osteopontin precursor [KO:K06250]
100009102  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100009235  [KO:K04439]
100009316  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100009352  TRPC1; short transient receptor potential channel 1 [KO:K04964]
100009366  [KO:K04997]
100009427  LHB; lutropin subunit beta precursor [KO:K08521]
100009481  CGA; glycoprotein hormones alpha chain precursor [KO:K08522]
100009505  [KO:K04958]
100009574  TRPC5; short transient receptor potential channel 5 [KO:K04968]
100009585  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
100037719  PRKCB; protein kinase C beta type isoform I [KO:K19662] [EC:2.7.11.13]
100037720  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100101555  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
100327259  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
100337822  [KO:K00922] [EC:2.7.1.153]
100340719  [KO:K04634]
100341204  [KO:K04439]
100341512  [KO:K05858] [EC:3.1.4.11]
100342605  [KO:K04943]
100342852  [KO:K04456] [EC:2.7.11.1]
100344241  [KO:K07828]
100345181  [KO:K00922] [EC:2.7.1.153]
100345250  [KO:K02649]
100345513  [KO:K05002]
100346309  [KO:K04854]
100346635  [KO:K04944]
100346748  [KO:K08551]
100346845  [KO:K04615]
100347345  [KO:K04371] [EC:2.7.11.24]
100347407  [KO:K04366] [EC:2.7.11.1]
100347487  [KO:K07827]
100347718  [KO:K04246]
100348561  [KO:K04371] [EC:2.7.11.24]
100348663  [KO:K00922] [EC:2.7.1.153]
100348672  [KO:K05858] [EC:3.1.4.11]
100350395  [KO:K05858] [EC:3.1.4.11]
100351872  [KO:K04945]
100352473  [KO:K04999]
100352824  [KO:K05252]
100353026  [KO:K04615]
100353706  [KO:K04456] [EC:2.7.11.1]
100353818  [KO:K04967]
100356806  [KO:K04959]
100357261  [KO:K04853]
100357841  [KO:K02649]
103347536  [KO:K05858] [EC:3.1.4.11]
108176286  [KO:K04955]
127486116  [KO:K04456] [EC:2.7.11.1]
127486418  [KO:K04855]
127486605  [KO:K02833]
127489236  [KO:K07827]
127489461  [KO:K04368] [EC:2.7.12.2]
127489908  [KO:K08374]
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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
ocu04010  MAPK signaling pathway
ocu04020  Calcium signaling pathway
ocu04151  PI3K-Akt signaling pathway
ocu04912  GnRH signaling pathway
ocu04913  Ovarian steroidogenesis
ocu04915  Estrogen signaling pathway
KO pathway
ko04929   

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