Entry Name GnRH secretion - Homo sapiens (human)
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 systemBRITE hierarchy
Pathway map Network nt06323 KISS1-GnRH-LH/FSH-E2 signaling
Element N00869 KISS1-KISS1R-PLCB-PKC signaling pathway
Organism Homo sapiens (human) [GN:
hsa ]
Gene 1081 CGA; glycoprotein hormones alpha chain isoform 2 precursor [KO:K08522 ]
208 AKT2; RAC-beta serine/threonine-protein kinase isoform 1 [KO:K04456 ] [EC:2.7.11.1 ]
2100 ESR2; estrogen receptor beta isoform 1 [KO:K08551 ]
23236 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform a [KO:K05858 ] [EC:3.1.4.11 ]
2550 GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform a precursor [KO:K04615 ]
2767 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
2776 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
2796 GNRH1; progonadoliberin-1 isoform 2 preproprotein [KO:K05252 ]
2797 GNRH2; progonadoliberin-2 isoform a preproprotein [KO:K05252 ]
2852 GPER1; G-protein coupled estrogen receptor 1 [KO:K04246 ]
348980 HCN1; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 [KO:K04954 ]
3708 ITPR1; inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 isoform 4 [KO:K04958 ]
3709 ITPR2; inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 isoform 1 [KO:K04959 ]
3710 ITPR3; inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 [KO:K04960 ]
3760 KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform 1 [KO:K04997 ]
3762 KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999 ]
3763 KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000 ]
3765 KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002 ]
3767 KCNJ11; ATP-sensitive inward rectifier potassium channel 11 isoform 1 [KO:K05004 ]
3780 KCNN1; small conductance calcium-activated potassium channel protein 1 isoform 1 [KO:K04942 ]
3781 KCNN2; small conductance calcium-activated potassium channel protein 2 isoform a [KO:K04943 ]
3782 KCNN3; small conductance calcium-activated potassium channel protein 3 isoform a [KO:K04944 ]
3783 KCNN4; intermediate conductance calcium-activated potassium channel protein 4 [KO:K04945 ]
3814 KISS1; metastasis-suppressor KiSS-1 preproprotein [KO:K23140 ]
3972 LHB; lutropin subunit beta precursor [KO:K08521 ]
408 ARRB1; beta-arrestin-1 isoform A [KO:K04439 ]
409 ARRB2; beta-arrestin-2 isoform 1 [KO:K04439 ]
5290 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform 1 [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform 1 [KO:K02649 ]
5296 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
5330 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform 1 [KO:K05858 ] [EC:3.1.4.11 ]
5331 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform 1 [KO:K05858 ] [EC:3.1.4.11 ]
5332 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform b [KO:K05858 ] [EC:3.1.4.11 ]
5604 MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform 1 [KO:K04368 ] [EC:2.7.12.2 ]
5605 MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform 1 [KO:K04369 ] [EC:2.7.12.2 ]
57657 HCN3; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 [KO:K04956 ]
5894 RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform b [KO:K04366 ] [EC:2.7.11.1 ]
610 HCN2; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 [KO:K04955 ]
6696 SPP1; osteopontin isoform OPN-a precursor [KO:K06250 ]
7220 TRPC1; short transient receptor potential channel 1 isoform 1 [KO:K04964 ]
7223 TRPC4; short transient receptor potential channel 4 isoform alpha [KO:K04967 ]
7224 TRPC5; short transient receptor potential channel 5 [KO:K04968 ]
775 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform 18 [KO:K04850 ]
776 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform b [KO:K04851 ]
778 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform 1 [KO:K04853 ]
779 CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
8503 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform 1 [KO:K02649 ]
8911 CACNA1I; voltage-dependent T-type calcium channel subunit alpha-1I isoform a [KO:K04856 ]
8912 CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H isoform a [KO:K04855 ]
8913 CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform 1 [KO:K04854 ]
9568 GABBR2; gamma-aminobutyric acid type B receptor subunit 2 precursor [KO:K04615 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
C04637 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
Reference Authors Ronnekleiv OK, Kelly MJ
Title Kisspeptin excitation of GnRH neurons.
Journal 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 Reference Authors Oakley AE, Clifton DK, Steiner RA
Title Kisspeptin signaling in the brain.
Journal Reference Authors Pinilla L, Aguilar E, Dieguez C, Millar RP, Tena-Sempere M
Title Kisspeptins and reproduction: physiological roles and regulatory mechanisms.
Journal Reference Authors d'Anglemont de Tassigny X, Colledge WH
Title The role of kisspeptin signaling in reproduction.
Journal Reference Authors Tena-Sempere M
Title Kisspeptin signaling in the brain: recent developments and future challenges.
Journal Reference Authors Colledge WH
Title Kisspeptins and GnRH neuronal signalling.
Journal 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 Reference Authors Piet R, de Croft S, Liu X, Herbison AE
Title Electrical properties of kisspeptin neurons and their regulation of GnRH neurons.
Journal 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 Reference Authors Ronnekleiv OK, Bosch MA, Zhang C
Title Regulation of endogenous conductances in GnRH neurons by estrogens.
Journal 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 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 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 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 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 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 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 Reference Authors Radovick S, Levine JE, Wolfe A
Title Estrogenic regulation of the GnRH neuron.
Journal Reference Authors Dungan HM, Clifton DK, Steiner RA
Title Minireview: kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion.
Journal 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 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 Related KO pathway
