GnRH signaling pathway - Homo sapiens (human)
Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnRHR is coupled to Gq/11 proteins to activate phospholipase C which transmits its signal to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG activates the intracellular protein kinase C (PKC) pathway and IP3 stimulates release of intracellular calcium. In addition to the classical Gq/11, coupling of Gs is occasionally observed in a cell-specific fashion. Signaling downstream of protein kinase C (PKC) leads to transactivation of the epidermal growth factor (EGF) receptor and activation of mitogen-activated protein kinases (MAPKs), including extracellular-signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPK. Active MAPKs translocate to the nucleus, resulting in activation of transcription factors and rapid induction of early genes.
Organismal Systems; Endocrine system
Pathway map Ortholog table
N00873 GnRH-GnRHR-PLCB-PKC signaling pathway
D00573 Goserelin acetate (JAN/USP)
D00988 Gonadorelin hydrochloride (USP)
D00989 Leuprolide acetate (USP)
D00990 Nafarelin acetate (USAN)
D01685 Cetrorelix acetate (JAN/USAN)
D01831 Buserelin acetate (JAN/USAN)
D03267 Gonadorelin diacetate (JP18)
D03701 Detirelix acetate (USAN)
D04302 Ganirelix acetate (JAN/USAN)
D04361 Gonadorelin acetate (USP)
D04823 Lutrelin acetate (USAN)
D05599 Prazarelix acetate (USAN)
D06248 Triptorelin pamoate (USAN)
D08635 Degarelix acetate (USAN)
D09400 Degarelix acetate (JAN)
D10888 Relugolix (JAN/USAN/INN)
D11609 Linzagolix choline (USAN)
Homo sapiens (human) [GN:
2796 GNRH1; gonadotropin releasing hormone 1 [KO: K05252]
2797 GNRH2; gonadotropin releasing hormone 2 [KO: K05252]
2798 GNRHR; gonadotropin releasing hormone receptor [KO: K04280]
468 ATF4; activating transcription factor 4 [KO: K04374]
2767 GNA11; G protein subunit alpha 11 [KO: K04635]
3708 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO: K04958]
3709 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO: K04959]
3710 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO: K04960]
815 CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO: K04515] [EC: 126.96.36.199]
817 CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO: K04515] [EC: 188.8.131.52]
816 CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO: K04515] [EC: 184.108.40.206]
818 CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO: K04515] [EC: 220.127.116.11]
775 CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO: K04850]
776 CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO: K04851]
778 CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO: K04853]
779 CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO: K04857]
998 CDC42; cell division cycle 42 [KO: K04393]
3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO: K04448]
3972 LHB; luteinizing hormone subunit beta [KO: K08521]
1081 CGA; glycoprotein hormones, alpha polypeptide [KO: K08522]
2488 FSHB; follicle stimulating hormone subunit beta [KO: K05250]
1839 HBEGF; heparin binding EGF like growth factor [KO: K08523]
2885 GRB2; growth factor receptor bound protein 2 [KO: K04364]
6654 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO: K03099]
6655 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO: K03099]
3265 HRAS; HRas proto-oncogene, GTPase [KO: K02833]
3845 KRAS; KRAS proto-oncogene, GTPase [KO: K07827]
4893 NRAS; NRAS proto-oncogene, GTPase [KO: K07828]
2002 ELK1; ETS transcription factor ELK1 [KO: K04375]
C01245 D-myo-Inositol 1,4,5-trisphosphate
Ruf F, Sealfon SC.
Genomics view of gonadotrope signaling circuits.
Harrison GS, Wierman ME, Nett TM, Glode LM.
Gonadotropin-releasing hormone and its receptor in normal and malignant cells.
Pawson AJ, McNeilly AS.
The pituitary effects of GnRH.
DeGroot LJ, Jameson JL (ed).
Endocrinology (Fifth edition)
Elsevier Saunders (2006)
Naor Z, Benard O, Seger R.
Activation of MAPK cascades by G-protein-coupled receptors: the case of gonadotropin-releasing hormone receptor.
Ruf F, Fink MY, Sealfon SC.
Structure of the GnRH receptor-stimulated signaling network: insights from genomics.
Farshori PQ, Shah BH, Arora KK, Martinez-Fuentes A, Catt KJ.
Activation and nuclear translocation of PKCdelta, Pyk2 and ERK1/2 by gonadotropin releasing hormone in HEK293 cells.
Shah BH, Catt KJ.
Matrix metalloproteinases in reproductive endocrinology.
Roelle S, Grosse R, Aigner A, Krell HW, Czubayko F, Gudermann T.
Matrix metalloproteinases 2 and 9 mediate epidermal growth factor receptor transactivation by gonadotropin-releasing hormone.
Signaling by G-protein-coupled receptor (GPCR): studies on the GnRH receptor.
hsa04060 Cytokine-cytokine receptor interaction
hsa04080 Neuroactive ligand-receptor interaction
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