Entry Name GnRH secretion
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 Orthology K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04246 GPER1, GPR30; G-protein coupled estrogen receptor 1
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04615 GABBR; gamma-aminobutyric acid type B receptor
K04634 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04635 GNA11; guanine nucleotide-binding protein subunit alpha-11
K04850 CACNA1C, CAV1.2; voltage-dependent calcium channel L type alpha-1C
K04851 CACNA1D, CAV1.3; voltage-dependent calcium channel L type alpha-1D
K04853 CACNA1F, CAV1.4; voltage-dependent calcium channel L type alpha-1F
K04854 CACNA1G, CAV3.1; voltage-dependent calcium channel T type alpha-1G
K04855 CACNA1H, CAV3.2; voltage-dependent calcium channel T type alpha-1H
K04856 CACNA1I, CAV3.3; voltage-dependent calcium channel T type alpha-1I
K04857 CACNA1S, CAV1.1; voltage-dependent calcium channel L type alpha-1S
K04942 KCNN1, KCA2.1; potassium intermediate/small conductance calcium-activated channel subfamily N member 1
K04943 KCNN2, KCA2.2; potassium intermediate/small conductance calcium-activated channel subfamily N member 2
K04944 KCNN3, KCA2.3; potassium intermediate/small conductance calcium-activated channel subfamily N member 3
K04945 KCNN4, KCA3.1; potassium intermediate/small conductance calcium-activated channel subfamily N member 4
K04954 HCN1; hyperpolarization activated cyclic nucleotide-gated potassium channel 1
K04955 HCN2; hyperpolarization activated cyclic nucleotide-gated potassium channel 2
K04956 HCN3; hyperpolarization activated cyclic nucleotide-gated potassium channel 3
K04958 ITPR1; inositol 1,4,5-triphosphate receptor type 1
K04959 ITPR2; inositol 1,4,5-triphosphate receptor type 2
K04960 ITPR3; inositol 1,4,5-triphosphate receptor type 3
K04964 TRPC1; transient receptor potential cation channel subfamily C member 1
K04967 TRPC4; transient receptor potential cation channel subfamily C member 4
K04968 TRPC5; transient receptor potential cation channel subfamily C member 5
K04997 KCNJ3, KIR3.1; potassium inwardly-rectifying channel subfamily J member 3
K04999 KCNJ5, KIR3.4; potassium inwardly-rectifying channel subfamily J member 5
K05000 KCNJ6, KIR3.2; potassium inwardly-rectifying channel subfamily J member 6
K05002 KCNJ9, KIR3.3; potassium inwardly-rectifying channel subfamily J member 9
K05004 KCNJ11, KIR6.2; potassium inwardly-rectifying channel subfamily J member 11
K05252 GNRH; gonadotropin-releasing hormone
K06250 SPP1, BNSP, OPN; secreted phosphoprotein 1
K07827 KRAS, KRAS2; GTPase KRas
K08521 LHB; lutropin subunit beta
K08522 CGA; glycoprotein hormones alpha chain
K08551 ESR2, NR3A2; estrogen receptor beta
K23140 KISS1; metastasis-suppressor KiSS-1
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.
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