KEGG   PATHWAY: ko04912
Entry
ko04912                     Pathway                                

Name
GnRH signaling pathway
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
ko04912  GnRH signaling pathway
ko04912

Disease
H00255  Hypogonadotropic hypogonadism
H00746  Hypokalemic periodic paralysis (HypoPP)
H00937  Precocious puberty
H01253  Isolated follicle-stimulating hormone deficiency
H01860  Abnormal pituitary gonadotropin secretion
Drug
D03694  Deslorelin (USAN/INN)
D04174  Fertirelin acetate (USAN)
Orthology
K05252  gonadotropin-releasing hormone
K04280  gonadotropin-releasing hormone receptor
K04632  guanine nucleotide-binding protein G(s) subunit alpha
K08041  adenylate cyclase 1 [EC:4.6.1.1]
K08042  adenylate cyclase 2 [EC:4.6.1.1]
K08043  adenylate cyclase 3 [EC:4.6.1.1]
K08044  adenylate cyclase 4 [EC:4.6.1.1]
K08045  adenylate cyclase 5 [EC:4.6.1.1]
K08046  adenylate cyclase 6 [EC:4.6.1.1]
K08047  adenylate cyclase 7 [EC:4.6.1.1]
K08048  adenylate cyclase 8 [EC:4.6.1.1]
K08049  adenylate cyclase 9 [EC:4.6.1.1]
K04345  protein kinase A [EC:2.7.11.11]
K04374  cyclic AMP-dependent transcription factor ATF-4
K04634  guanine nucleotide-binding protein G(q) subunit alpha
K04635  guanine nucleotide-binding protein subunit alpha-11
K05858  phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K04958  inositol 1,4,5-triphosphate receptor type 1
K04959  inositol 1,4,5-triphosphate receptor type 2
K04960  inositol 1,4,5-triphosphate receptor type 3
K02183  calmodulin
K04515  calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17]
K02677  classical protein kinase C alpha type [EC:2.7.11.13]
K19662  classical protein kinase C beta type [EC:2.7.11.13]
K06068  novel protein kinase C delta type [EC:2.7.11.13]
K04850  voltage-dependent calcium channel L type alpha-1C
K04851  voltage-dependent calcium channel L type alpha-1D
K04853  voltage-dependent calcium channel L type alpha-1F
K04857  voltage-dependent calcium channel L type alpha-1S
K04416  mitogen-activated protein kinase kinase kinase 1 [EC:2.7.11.25]
K04420  mitogen-activated protein kinase kinase kinase 2 [EC:2.7.11.25]
K04421  mitogen-activated protein kinase kinase kinase 3 [EC:2.7.11.25]
K04428  mitogen-activated protein kinase kinase kinase 4 [EC:2.7.11.25]
K04432  mitogen-activated protein kinase kinase 3 [EC:2.7.12.2]
K04433  mitogen-activated protein kinase kinase 6 [EC:2.7.12.2]
K04441  p38 MAP kinase [EC:2.7.11.24]
K04464  mitogen-activated protein kinase 7 [EC:2.7.11.24]
K16342  cytosolic phospholipase A2 [EC:3.1.1.4]
K01115  phospholipase D1/2 [EC:3.1.4.4]
K05704  tyrosine-protein kinase Src [EC:2.7.10.2]
K04393  cell division control protein 42
K04430  mitogen-activated protein kinase kinase 4 [EC:2.7.12.2]
K04431  mitogen-activated protein kinase kinase 7 [EC:2.7.12.2]
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04448  transcription factor AP-1
K08521  lutropin subunit beta
K08522  glycoprotein hormones alpha chain
K05250  follitropin subunit beta
K05871  focal adhesion kinase 2 [EC:2.7.10.2]
K01398  matrix metalloproteinase-2 (gelatinase A) [EC:3.4.24.24]
K07763  matrix metalloproteinase-14 (membrane-inserted) [EC:3.4.24.80]
K08523  heparin-binding EGF-like growth factor
K04361  epidermal growth factor receptor [EC:2.7.10.1]
K04364  growth factor receptor-bound protein 2
K03099  son of sevenless
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04375  ETS domain-containing protein Elk-1
K09203  early growth response protein 1
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
ko04010  MAPK signaling pathway
ko04020  Calcium signaling pathway
ko04024  cAMP signaling pathway
ko04060  Cytokine-cytokine receptor interaction
ko04080  Neuroactive ligand-receptor interaction
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