Entry
Name
GnRH secretion - Rattus norvegicus (rat)
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
BRITE hierarchy
Pathway map
Ortholog table
Organism
Rattus norvegicus (rat) [GN:
rno ]
Gene
289023 Kiss1; metastasis-suppressor KiSS-1 precursor [KO:K23140 ]
81666 Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
81662 Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
24654 Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858 ] [EC:3.1.4.11 ]
29322 Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858 ] [EC:3.1.4.11 ]
85240 Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858 ] [EC:3.1.4.11 ]
25031 Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858 ] [EC:3.1.4.11 ]
25262 Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958 ]
81678 Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959 ]
25679 Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960 ]
84390 Hcn1; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 [KO:K04954 ]
114244 Hcn2; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 [KO:K04955 ]
114245 Hcn3; potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 [KO:K04956 ]
29717 Cacna1g; voltage-dependent T-type calcium channel subunit alpha-1G isoform 1 [KO:K04854 ]
114862 Cacna1h; voltage-dependent T-type calcium channel subunit alpha-1H [KO:K04855 ]
56827 Cacna1i; voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856 ]
89821 Trpc1; short transient receptor potential channel 1 isoform 2 [KO:K04964 ]
84494 Trpc4; short transient receptor potential channel 4 isoform beta [KO:K04967 ]
140933 Trpc5; short transient receptor potential channel 5 [KO:K04968 ]
83535 Kcnj11; ATP-sensitive inward rectifier potassium channel 11 [KO:K05004 ]
50599 Kcnj3; G protein-activated inward rectifier potassium channel 1 [KO:K04997 ]
25743 Kcnj6; G protein-activated inward rectifier potassium channel 2 isoform 1 [KO:K05000 ]
116560 Kcnj9; G protein-activated inward rectifier potassium channel 3 [KO:K05002 ]
29713 Kcnj5; G protein-activated inward rectifier potassium channel 4 [KO:K04999 ]
81657 Gabbr1; gamma-aminobutyric acid type B receptor subunit 1 precursor [KO:K04615 ]
83633 Gabbr2; gamma-aminobutyric acid type B receptor subunit 2 precursor [KO:K04615 ]
54261 Kcnn1; small conductance calcium-activated potassium channel protein 1 [KO:K04942 ]
54262 Kcnn2; small conductance calcium-activated potassium channel protein 2 isoform 2 [KO:K04943 ]
54263 Kcnn3; small conductance calcium-activated potassium channel protein 3 [KO:K04944 ]
65206 Kcnn4; intermediate conductance calcium-activated potassium channel protein 4 isoform a [KO:K04945 ]
682930 Cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
24239 Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850 ]
29716 Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851 ]
114493 Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853 ]
367858 Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833 ]
58960 Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369 ] [EC:2.7.12.2 ]
25513 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
60664 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
29741 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
85243 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
170911 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
366508 Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
134484121 LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922 ] [EC:2.7.1.153 ]
171104 Gper1; G-protein coupled estrogen receptor 1 [KO:K04246 ]
25329 Lhb; lutropin subunit beta isoform 1 precursor [KO:K08521 ]
116700 Cga; glycoprotein hormones alpha chain precursor [KO:K08522 ]
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 pathway
KO pathway
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