KEGG   PATHWAY: rno04912
Entry
rno04912                    Pathway                                

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
Pathway map
rno04912  GnRH signaling pathway
rno04912

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
25194  Gnrh1; progonadoliberin-1 precursor [KO:K05252]
81668  Gnrhr; gonadotropin-releasing hormone receptor [KO:K04280]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
305509  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
64508  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
54223  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:4.6.1.1]
84420  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
29241  Adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
302950  Adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
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]
50663  Calm2; calmodulin-2 [KO:K02183]
24242  Calm1; calmodulin-1 [KO:K02183]
24244  Calm3; calmodulin-3 [KO:K02183]
364774  Calml5; calmodulin-like protein 5 [KO:K02183]
307100  Calml3; calmodulin-like protein 3 [KO:K02183]
691455  Calml4; calmodulin-like protein 4 [KO:K02183]
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]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
170538  Prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
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]
116667  Map3k1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
171492  Map3k2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
303604  Map3k3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
308106  Map3k4; mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
303200  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
114495  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
114509  Mapk7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
296091  Pla2g4e; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
24653  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
311341  Pla2g4b; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
691905  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
691907  Pla2g4f; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
691810  Pla2g4c; phospholipase A2, group IVC [KO:K16342] [EC:3.1.1.4]
25097  Pld2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
25096  Pld1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
83805  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
64465  Cdc42; cell division control protein 42 homolog [KO:K04393]
287398  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
363855  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
25272  Mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
50658  Mapk9; mitogen-activated protein kinase 9 isoform 2 [KO:K04440] [EC:2.7.11.24]
116554  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
24516  Jun; transcription factor AP-1 [KO:K04448]
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]
50646  Ptk2b; protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
81686  Mmp2; 72 kDa type IV collagenase precursor [KO:K01398] [EC:3.4.24.24]
81707  Mmp14; matrix metalloproteinase-14 precursor [KO:K07763] [EC:3.4.24.80]
25433  Hbegf; proheparin-binding EGF-like growth factor precursor [KO:K08523]
24329  Egfr; epidermal growth factor receptor precursor [KO:K04361] [EC:2.7.10.1]
81504  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
85384  Sos2; son of sevenless homolog 2 [KO:K03099]
313845  Sos1; son of sevenless homolog 1 [KO:K03099]
293621  Hras; GTPase HRas [KO:K02833]
367858  GTPase HRas [KO:K02833]
24525  Kras; GTPase KRas [KO:K07827]
24605  Nras; GTPase NRas [KO:K07828]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
314436  Elk1; ETS domain-containing protein Elk-1 [KO:K04375]
24330  Egr1; early growth response protein 1 [KO:K09203]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00219  Arachidonate
C00416  Phosphatidate
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
  Authors
Ruf F, Sealfon SC.
  Title
Genomics view of gonadotrope signaling circuits.
  Journal
Trends Endocrinol Metab 15:331-8 (2004)
DOI:10.1016/j.tem.2004.07.008
Reference
  Authors
Harrison GS, Wierman ME, Nett TM, Glode LM.
  Title
Gonadotropin-releasing hormone and its receptor in normal and malignant cells.
  Journal
Endocr Relat Cancer 11:725-48 (2004)
DOI:10.1677/erc.1.00777
Reference
  Authors
Pawson AJ, McNeilly AS.
  Title
The pituitary effects of GnRH.
  Journal
Anim Reprod Sci 88:75-94 (2005)
DOI:10.1016/j.anireprosci.2005.05.010
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
Trends Endocrinol Metab 11:91-9 (2000)
DOI:10.1016/S1043-2760(99)00232-5
Reference
  Authors
Ruf F, Fink MY, Sealfon SC.
  Title
Structure of the GnRH receptor-stimulated signaling network: insights from genomics.
  Journal
Front Neuroendocrinol 24:181-99 (2003)
DOI:10.1016/S0091-3022(03)00027-X
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
J Steroid Biochem Mol Biol 85:337-47 (2003)
DOI:10.1016/S0960-0760(03)00226-7
Reference
  Authors
Shah BH, Catt KJ.
  Title
Matrix metalloproteinases in reproductive endocrinology.
  Journal
Trends Endocrinol Metab 15:47-9 (2004)
DOI:10.1016/j.tem.2004.01.004
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
J Biol Chem 278:47307-18 (2003)
DOI:10.1074/jbc.M304377200
Reference
  Authors
Naor Z
  Title
Signaling by G-protein-coupled receptor (GPCR): studies on the GnRH receptor.
  Journal
Front Neuroendocrinol 30:10-29 (2009)
DOI:10.1016/j.yfrne.2008.07.001
Related
pathway
rno04010  MAPK signaling pathway
rno04020  Calcium signaling pathway
rno04024  cAMP signaling pathway
rno04060  Cytokine-cytokine receptor interaction
rno04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   

DBGET integrated database retrieval system