Entry
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
BRITE hierarchy
Pathway map
Ortholog table
Drug
D04174 Fertirelin acetate (USAN)
Orthology
K05252 gonadotropin-releasing hormone
K04280 gonadotropin-releasing hormone receptor
K04632 guanine nucleotide-binding protein G(s) subunit alpha
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
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
K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17 ]
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
K04393 cell division control protein 42
K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04448 transcription factor AP-1
K08522 glycoprotein hormones alpha chain
K05250 follitropin subunit beta
K08523 heparin-binding EGF-like growth factor
K04364 growth factor receptor-bound protein 2
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04375 ETS domain-containing protein Elk-1
K09203 early growth response protein 1
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
ko04060 Cytokine-cytokine receptor interaction
ko04080 Neuroactive ligand-receptor interaction
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