Entry
Name
GnRH signaling pathway - Rattus norvegicus (rat)
Description
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.
Class
Organismal Systems; Endocrine system
BRITE hierarchy
Pathway map
Ortholog table
Organism
Rattus norvegicus (rat) [GN:
rno ]
Gene
81668 Gnrhr; gonadotropin-releasing hormone receptor [KO:K04280 ]
24896 Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632 ]
79255 Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
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 ]
25400 Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515 ] [EC:2.7.11.17 ]
24246 Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515 ] [EC:2.7.11.17 ]
24245 Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform 2 [KO:K04515 ] [EC:2.7.11.17 ]
171140 Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515 ] [EC:2.7.11.17 ]
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 ]
682930 Cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
64465 Cdc42; cell division control protein 42 homolog [KO:K04393 ]
363855 Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform 1 [KO:K04431 ] [EC:2.7.12.2 ]
25329 Lhb; lutropin subunit beta isoform 1 precursor [KO:K08521 ]
116700 Cga; glycoprotein hormones alpha chain precursor [KO:K08522 ]
25447 Fshb; follitropin subunit beta precursor [KO:K05250 ]
25433 Hbegf; proheparin-binding EGF-like growth factor precursor [KO:K08523 ]
81504 Grb2; growth factor receptor-bound protein 2 [KO:K04364 ]
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 ]
314436 Elk1; ETS domain-containing protein Elk-1 [KO:K04375 ]
24330 Egr1; early growth response protein 1 [KO:K09203 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference
Authors
Ruf F, Sealfon SC.
Title
Genomics view of gonadotrope signaling circuits.
Journal
Reference
Authors
Harrison GS, Wierman ME, Nett TM, Glode LM.
Title
Gonadotropin-releasing hormone and its receptor in normal and malignant cells.
Journal
Reference
Authors
Pawson AJ, McNeilly AS.
Title
The pituitary effects of GnRH.
Journal
Reference
Authors
DeGroot LJ, Jameson JL (ed).
Title
Endocrinology (Fifth edition)
Journal
Elsevier Saunders (2006)
Reference
Authors
Naor Z, Benard O, Seger R.
Title
Activation of MAPK cascades by G-protein-coupled receptors: the case of gonadotropin-releasing hormone receptor.
Journal
Reference
Authors
Ruf F, Fink MY, Sealfon SC.
Title
Structure of the GnRH receptor-stimulated signaling network: insights from genomics.
Journal
Reference
Authors
Farshori PQ, Shah BH, Arora KK, Martinez-Fuentes A, Catt KJ.
Title
Activation and nuclear translocation of PKCdelta, Pyk2 and ERK1/2 by gonadotropin releasing hormone in HEK293 cells.
Journal
Reference
Authors
Shah BH, Catt KJ.
Title
Matrix metalloproteinases in reproductive endocrinology.
Journal
Reference
Authors
Roelle S, Grosse R, Aigner A, Krell HW, Czubayko F, Gudermann T.
Title
Matrix metalloproteinases 2 and 9 mediate epidermal growth factor receptor transactivation by gonadotropin-releasing hormone.
Journal
Reference
Authors
Naor Z
Title
Signaling by G-protein-coupled receptor (GPCR): studies on the GnRH receptor.
Journal
Related pathway
rno04060 Cytokine-cytokine receptor interaction
rno04080 Neuroactive ligand-receptor interaction
KO pathway
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