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GnRH1 receptor

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Target id: 256

Nomenclature: GnRH1 receptor

Family: Gonadotrophin-releasing hormone receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 328 4q13.2 GNRHR gonadotropin releasing hormone receptor 16,27-28,42,44,51,63
Mouse 7 327 5 43.56 cM Gnrhr gonadotropin releasing hormone receptor 79,92
Rat 7 327 14p21 Gnrhr gonadotropin releasing hormone receptor 25,39,45,64,75
Previous and Unofficial Names Click here for help
luteinizing hormone-releasing hormone (LHRH) receptor | GNRHR1 | LHRH receptor | Type I GnRHR | gnRH receptor | GnRH-R | GnRH I receptor | GnRHR | luliberin receptor | LHRHR
Database Links Click here for help
Specialist databases
GPCRdb gnrhr_human (Hs), gnrhr_mouse (Mm), gnrhr_rat (Rn)
Other databases
Alphafold P30968 (Hs), Q01776 (Mm), P30969 (Rn)
ChEMBL Target CHEMBL1855 (Hs), CHEMBL3232679 (Mm), CHEMBL3066 (Rn)
DrugBank Target P30968 (Hs)
Ensembl Gene ENSG00000109163 (Hs), ENSMUSG00000029255 (Mm), ENSRNOG00000002011 (Rn)
Entrez Gene 2798 (Hs), 14715 (Mm), 81668 (Rn)
Human Protein Atlas ENSG00000109163 (Hs)
KEGG Gene hsa:2798 (Hs), mmu:14715 (Mm), rno:81668 (Rn)
OMIM 138850 (Hs)
Orphanet ORPHA122226 (Hs)
Pharos P30968 (Hs)
RefSeq Nucleotide NM_000406 (Hs), NM_010323 (Mm), NM_031038 (Rn)
RefSeq Protein NP_000397 (Hs), NP_034453 (Mm), NP_112300 (Rn)
UniProtKB P30968 (Hs), Q01776 (Mm), P30969 (Rn)
Wikipedia GNRHR (Hs)
Natural/Endogenous Ligands Click here for help
GnRH I {Sp: Human, Mouse, Rat}
GnRH II {Sp: Human}
Comments: GnRH I is the more potent agonist
Potency order of endogenous ligands (Human)
GnRH I (GNRH1, P01148) > GnRH II (GNRH2, O43555)  [60]

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
buserelin Peptide Approved drug Hs Full agonist 9.5 – 10.4 pKd 65-66
⤷ pKd 9.5 – 10.4 (Kd 3x10-10 – 4x10-11 M) [65-66]
deslorelin Peptide Hs Full agonist 9.4 – 10.0 pKd 65
⤷ pKd 9.4 – 10.0 (Kd 4x10-10 – 1x10-10 M) [65]
histerelin Peptide Hs Full agonist 9.0 – 10.4 pKd 65
⤷ pKd 9.0 – 10.4 (Kd 1x10-9 – 4x10-11 M) [65]
alarelin Peptide Hs Full agonist 9.4 – 9.7 pKd 65
⤷ pKd 9.4 – 9.7 (Kd 4x10-10 – 2x10-10 M) [65]
Conditions: using the ethyl amide form of alarelin
[125I][des-Gly10,D-Ala6]GnRH N-ethylamide Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 9.3 pKd 1
⤷ pKd 9.3 [1]
[125I]triptorelin Peptide Ligand is labelled Ligand is radioactive Rn Full agonist 9.3 pKd 22
⤷ pKd 9.3 [22]
fertirelin Peptide Hs Full agonist 9.1 – 9.1 pKd 65
⤷ pKd 9.1 – 9.1 (Kd 9x10-10 – 8x10-10 M) [65]
[125I][Tyr5,DAla6,NMeLeu7,Pro9-NEt]GnRH Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 8.5 pKd 76
⤷ pKd 8.5 [76]
GnRH III Peptide Hs Full agonist 8.2 pKd 58
⤷ pKd 8.2 (Kd 6.3x10-9 M) [58]
GnRH I {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Hs Full agonist 7.7 – 8.5 pKd 65
⤷ pKd 7.7 – 8.5 (Kd 2.2x10-8 – 2.9x10-9 M) [65]
[125I]buserelin Peptide Ligand is labelled Ligand is radioactive Rn Full agonist 7.4 pKd 46
⤷ pKd 7.4 (Kd 4x10-8 M) [46]
buserelin Peptide Approved drug Hs Full agonist 9.4 – 10.0 pKi 65
⤷ pKi 9.4 – 10.0 (Ki 4x10-10 – 1x10-10 M) [65]
deslorelin Peptide Hs Full agonist 9.1 – 10.0 pKi 65
⤷ pKi 9.1 – 10.0 (Ki 8x10-10 – 1x10-10 M) [65]
triptorelin Peptide Approved drug Hs Full agonist 9.3 – 9.5 pKi 6
⤷ pKi 9.3 – 9.5 (Ki 5.1x10-10 – 3.2x10-10 M) [6]
histerelin Peptide Hs Full agonist 8.7 – 9.7 pKi 65
⤷ pKi 8.7 – 9.7 (Ki 1.9x10-9 – 2x10-10 M) [65]
alarelin Peptide Hs Full agonist 9.1 – 9.3 pKi 65
⤷ pKi 9.1 – 9.3 (Ki 9x10-10 – 5x10-10 M) [65]
Conditions: using the ethyl amide form of alarelin
fertirelin Peptide Hs Full agonist 9.0 – 9.1 pKi 65
⤷ pKi 9.0 – 9.1 (Ki 1x10-9 – 7x10-10 M) [65]
leuprolide Peptide Approved drug Primary target of this compound Hs Full agonist 8.5 – 9.1 pKi 87
⤷ pKi 8.5 – 9.1 (Ki 3.16x10-9 – 7.9x10-10 M) [87]
triptorelin Peptide Approved drug Rn Full agonist 8.5 – 8.8 pKi 6
⤷ pKi 8.5 – 8.8 [6]
[His5,D-Tyr6]GnRH Peptide Hs Full agonist 7.8 – 8.4 pKi 87
⤷ pKi 7.8 – 8.4 [87]
GnRH I {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Hs Full agonist 7.3 – 8.4 pKi 6,65,87
⤷ pKi 7.9 – 8.4 (Ki 1.3x10-8 – 4x10-9 M) [65]
pKi 7.3 – 8.4 [6,87]
GnRH I {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Rn Full agonist 6.8 pKi 6
⤷ pKi 6.8 [6]
buserelin Peptide Approved drug Hs Full agonist 10.5 pEC50 66
⤷ pEC50 10.5 (EC50 3x10-11 M) [66]
GnRH I {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Hs Full agonist 10.0 pEC50 66
⤷ pEC50 10.0 (EC50 1x10-10 M) [66]
buserelin Peptide Approved drug Mm Full agonist 9.3 – 10.1 pEC50 66
⤷ pEC50 9.3 – 10.1 (EC50 4.6x10-10 – 9x10-11 M) [66]
GnRH I {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Mm Full agonist 7.8 – 7.9 pEC50 66
⤷ pEC50 7.8 – 7.9 (EC50 1.7x10-8 – 1.2x10-8 M) [66]
[des-Gly10,D-Ala6]GnRH N-ethylamide Peptide Mm Full agonist 9.9 pIC50 79
⤷ pIC50 9.9 [79]
leuprolide Peptide Approved drug Rn Full agonist 9.1 pIC50 46
⤷ pIC50 9.1 [46]
GnRH I {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Hs Full agonist 8.6 pIC50 55
⤷ pIC50 8.6 [55]
GnRH I {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Mm Full agonist 8.3 pIC50 79
⤷ pIC50 8.3 [79]
GnRH I {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Rn Full agonist 7.7 pIC50 46
⤷ pIC50 7.7 [46]
[D-Lys6]GnRH-II Peptide Hs Full agonist 7.6 pIC50 29
⤷ pIC50 7.6 (IC50 2.6x10-8 M) [29]
GnRH II {Sp: Human} Peptide Ligand is endogenous in the given species Hs Full agonist 7.1 – 7.9 pIC50 29,55,86
⤷ pIC50 7.1 – 7.9 [29,55,86]
[Gln8]GnRH Peptide Hs Full agonist 7.1 pIC50 55
⤷ pIC50 7.1 [55]
[Trp8]GnRH Peptide Hs Full agonist 7.0 pIC50 55
⤷ pIC50 7.0 [55]
[Tyr8]GnRH Peptide Hs Full agonist 6.7 pIC50 55
⤷ pIC50 6.7 [55]
[Ser8]GnRH Peptide Hs Full agonist 6.2 pIC50 55
⤷ pIC50 6.2 [55]
[125I]GnRH I (human, mouse, rat) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist - -
⤷
goserelin Peptide Approved drug Primary target of this compound Hs Full agonist - -
⤷
histrelin Peptide Approved drug Hs Full agonist - -
⤷
nafarelin Peptide Approved drug Primary target of this compound Hs Full agonist - -
⤷
View species-specific agonist tables
Agonist Comments
Although GnRH II has been shown to be present in several tissues in man, a full length GnRH II receptor transcript has not been identified, although it is present in other mammals. Thus, in man there is one functional receptor with two endogenous ligands that both have a high affinity for the receptor [60].

Several peptide agonist derivatives of GnRH are being used to design so-called bioconjugates, where the peptide is used as a targeting moiety and a chemotherapeutic agent is coupled for the cytotoxic effect (for reviews see [54] and [84]).

The receptor binding kinetics (i.e. association rate and dissociation rates) of some peptide agonists have also been determined in Nederpelt et al., 2016 [65].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]cetrorelix Peptide Ligand is labelled Ligand is radioactive Hs Antagonist 9.7 pKd 36
⤷ pKd 9.7 [36]
[3H]NBI-49202 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 9.7 pKd 89
⤷ pKd 9.7 [89]
D-23487 Peptide Hs Antagonist 10.0 pKi 8
⤷ pKi 10.0 [8]
sufugolix Small molecule or natural product Hs Antagonist 10.0 pKi 83
⤷ pKi 10.0 [83]
cetrorelix Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Antagonist 9.3 – 10.0 pKi 7-8,87
⤷ pKi 9.3 – 10.0 [7-8,87]
antarelix Peptide Hs Antagonist 9.6 pKi 8
⤷ pKi 9.6 [8]
iturelix Peptide Hs Antagonist 9.5 pKi 80
⤷ pKi 9.5 (Ki 3.5x10-10 M) [80]
abarelix Peptide Approved drug Primary target of this compound Hs Antagonist 9.1 – 9.5 pKi 87
⤷ pKi 9.1 – 9.5 (Ki 7.9x10-10 – 3.2x10-10 M) [87]
NBI-42902 Small molecule or natural product Hs Antagonist 9.0 – 9.5 pKi 87
⤷ pKi 9.1 – 9.5 [87]
pKi 9.0 – 9.3 [87]
elagolix Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Antagonist 9.1 pKi 12,48
⤷ pKi 9.1 (Ki 9x10-10 M) [12,48]
degarelix Peptide Approved drug Primary target of this compound Hs Antagonist 8.8 pKi 94
⤷ pKi 8.8 (Ki 1.7x10-9 M) [94]
D-24710 Peptide Hs Antagonist 8.6 pKi 8
⤷ pKi 8.6 [8]
FD-1 Small molecule or natural product Hs Antagonist 8.3 pKi 34
⤷ pKi 8.3 [34]
compound 4 [PMID: 32677155] Small molecule or natural product Rn Antagonist 8.3 pKi 9
⤷ pKi 8.3 (Ki 5.49x10-9 M) [9]
Description: Binding affinity to rat GnRH receptors as determined from competitive binding studies against [125I]buserelin.
CMPD-1 Small molecule or natural product Hs Antagonist 8.2 pKi 1
⤷ pKi 8.2 [1]
cyclorelix Peptide Hs Antagonist 7.9 pKi 8
⤷ pKi 7.9 [8]
T-98475 Small molecule or natural product Hs Antagonist 9.7 pIC50 17
⤷ pIC50 9.7 [17]
merigolix Small molecule or natural product Hs Antagonist 9.6 pIC50 43
⤷ pIC50 9.6 (IC50 2.5x10-10 M) [43]
relugolix Small molecule or natural product Approved drug Hs Antagonist 9.5 pIC50 62
⤷ pIC50 9.5 (IC50 3.3x10-10 M) [62]
relugolix Small molecule or natural product Approved drug Rn Antagonist 9.5 pIC50 62
⤷ pIC50 9.5 (IC50 3.3x10-10 M) [62]
IN-3 Small molecule or natural product Hs Antagonist 9.2 pIC50 5,38
⤷ pIC50 9.2 (IC50 6x10-10 M) [5,38]
[Ac-D-2Nal1,D4CPA2,D-3Pal3,6,Leu8, D-Ala10]GnRH-II Peptide Hs Antagonist 9.2 pIC50 29
⤷ pIC50 9.2 (IC50 6.6x10-10 M) [29]
iturelix Peptide Hs Antagonist 9.0 pIC50 67
⤷ pIC50 9.0 (IC50 1.05x10-9 M) [67]
IN-3 Small molecule or natural product Rn Antagonist 8.8 pIC50 5
⤷ pIC50 8.8 (IC50 1.7x10-9 M) [5]
cetrorelix Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Antagonist 8.7 pIC50 67
⤷ pIC50 8.7 (IC50 1.98x10-9 M) [67]
WAY-207024 Small molecule or natural product Hs Antagonist 7.9 pIC50 73
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [73]
BAY1214784 Small molecule or natural product Hs Antagonist 7.7 pIC50 70
⤷ pIC50 7.7 (IC50 2.1x10-8 M) [70]
Description: Antagonism of buserelin-induced GnRHR activation in a proprietary IP-One HTRF assay
linzagolix Small molecule or natural product Approved drug Hs Antagonist 7.4 pIC50 90
⤷ pIC50 7.4 (IC50 3.67x10-8 M) [90]
Description: Inhibition of GnRH-stimulated Ca2+ flux in HEK293 cells stably expressing hGnRHR.
WAY-207024 Small molecule or natural product Rn Antagonist 7.2 pIC50 73
⤷ pIC50 7.2 (IC50 7.1x10-8 M) [73]
linzagolix Small molecule or natural product Approved drug Monkey Antagonist 6.3 pIC50 90
⤷ pIC50 6.3 (IC50 4.42x10-7 M) [90]
Description: Inhibition of GnRH-induced Ca2+ flux in HEK293 cells stably expressing cynomolgus monkey GnRHR
View species-specific antagonist tables
Antagonist Comments
In addition, non-peptide GnRH receptor antagonists have been reviewed recently [10,33]

The GnRH-I receptor has been shown to be highly sensitive polymorphisms, which often result in lower plasma membrane expression due to retention or degredation in the ER. Hence, so-called pharmacochaperones are being developed for this receptor. Some GnRH receptor antagonists have been reported as pharmacochaperons, e.g. IN3 and TAK-013 (for review see [19])

Note: antarelix is sometimes refered to as teverelix, and TAK-385 is now named relugolix.

There are some novel developments with regard to small molecule GnRH receptor antagonists:
- designed as tracer ligands for PET studies in vivo in rats [9,37,69]
- designed as a tracer ligand for SPECT studies in vivo in rats [30]
- conjugated with cytotoxic agents, e.g. paclitaxel-degarelix [95], or with a fluorescent probe for (metastatic) imaging [21,53].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CMPD-1 Small molecule or natural product Hs Negative 7.8 pIC50 88
⤷ pIC50 7.8 [88]
FD-1 Small molecule or natural product Hs Negative 5.3 pIC50 34
⤷ pIC50 5.3 [34]
5-(N,N-hexamethylene)-amiloride Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Negative 4.3 pIC50 34
⤷ pIC50 4.3 [34]
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  77,85
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Other - See Comments
Comments:  GnRH receptor coupling to Gi has been demonstrated in several cancer cells, but also in rat pituitary cells.
References:  60
Tissue Distribution Click here for help
Ovary: granulosa-luteal cells.
Species:  Human
Technique:  RT-PCR.
References:  74
Pituitary, breast, ovary, prostate.
Species:  Human
Technique:  RT-PCR.
References:  40
Liver, heart, skeletal muscle, kidney, placenta, pituitary.
Species:  Human
Technique:  RT-PCR.
References:  41
Pituitary.
Species:  Human
Technique:  RT-PCR.
References:  61,82
Peripheral blood mononuclear cells.
Species:  Human
Technique:  RT-PCR.
References:  13
Sperm, anterior pituitary.
Species:  Human
Technique:  Immunohistochemistry.
References:  50
Pituitary.
Species:  Human
Technique:  Immunohistochemistry.
References:  47
Heart (cardiomyocytes)
Species:  Mouse
Technique:  Ca2+ release in cardiomyocytes
References:  24
Heart (cardiomyocytes)
Species:  Mouse
Technique:  Cardiomyocyte contractility
References:  24
Anterior pituitary, ovary.
Species:  Rat
Technique:  Radioligand binding.
References:  78
Mammary gland.
Species:  Rat
Technique:  RT-PCR.
References:  52
Prostate.
Species:  Rat
Technique:  RT-PCR.
References:  49
Pituitary.
Species:  Rat
Technique:  Radioligand binding.
References:  18,20,31,56
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of IP levels in immature and mature rat ovarian granulosa cells endogenously expressing the GnRH receptor.
Species:  Rat
Tissue:  Ovarian granulosa cells.
Response measured:  Stimulation of IP accumulation.
References:  2
Measurement of IP levels in COS-M6 cells transfected with the rat GnRH receptor.
Species:  Rat
Tissue:  COS-M6 cells.
Response measured:  Stimulation of IP accumulation.
References:  75
Measurement of arachidonic acid release from mouse pituitary gonadotrope alpha T3-1 cells endogenously expressing the GnRH receptor.
Species:  Mouse
Tissue:  T3-1 cells.
Response measured:  Stimulation of arachidonic acid production.
References:  77
Measurement of IP levels in mouse pituitary gonadotrope alpha T3-1 cells endogenously expressing the GnRH receptor.
Species:  Mouse
Tissue:  T3-1 cells.
Response measured:  Stimulation of IP accumulation.
References:  3-4,77,85
Measurement of IP levels in HEK 293 cells transfected with the rat GnRH receptor.
Species:  Rat
Tissue:  HEK 293 cells.
Response measured:  Stimulation of IP accumulation.
References:  3,32
Measurement of Ca2+ levels in mouse pituitary gonadotrope alpha T3-1 cells endogenously expressing the GnRH receptor.
Species:  Mouse
Tissue:  T3-1 cells.
Response measured:  Stimulation of calcium mobilisation.
References:  3-4
Measurement of Ca2+ levels in HEK 293 cells transfected with the rat GnRH receptor.
Species:  Rat
Tissue:  HEK 293 cells.
Response measured:  Stimulation of calcium mobilisation.
References:  3
Measurement of in Ca2+ levels in immature and mature rat ovarian granulosa cells endogenously expressing the GnRH receptor.
Species:  Rat
Tissue:  Ovarian granulosa cells.
Response measured:  Stimulation of calcium mobilisation.
References:  2
Measurement of phosphatidylethanol (PEt) in mouse pituitary gonadotrope alpha T3-1 cells endogenously expressing the GnRH receptor.
Species:  Mouse
Tissue:  T3-1 cells.
Response measured:  Stimulation of PEt production.
References:  68,77
Measurement of IP levels in COS-7 cells transfected with the rat GnRH receptor.
Species:  Rat
Tissue:  COS-7 cells.
Response measured:  Stimulation of IP accumulation.
References:  32
Measurement of IP levels in COS-M6 cells transfected with the mouse GnRH receptor.
Species:  Mouse
Tissue:  COS-M6 cells.
Response measured:  Stimulation of IP accumulation.
References:  75
Measurement of prolactin release from GH3 cells transfected with the rat GnRH receptor.
Species:  Rat
Tissue:  GGH3-1' cells.
Response measured:  Prolactin release by a cAMP-dependent mechanism.
References:  46
Measurement of Ca2+ in Xenopus oocytes transfected with the mouse GnRH receptor.
Species:  Mouse
Tissue:  Xenopus oocytes.
Response measured:  Stimulation of calcium mobilisation.
References:  79
Measurement of IP levels in Sf9 insect cells transfected with the rat GnRH receptor.
Species:  Rat
Tissue:  Sf9 cells.
Response measured:  Stimulation of IP accumulation.
References:  22
Measurement of cAMP levels in Sf9 insect cells transfected with the rat GnRH receptor.
Species:  Rat
Tissue:  Sf9 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  22
Measurement of IP levels in CHO cells transfected with the human GnRH receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Stimulation of IP accumulation.
References:  23
Measurement of arachidonic acid release from CHO cells transfected with the human GnRH receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Stimulation of arachidonic acid production.
References:  83
Measurement of IP levels in RBL cells transfected with the human GnRH receptor.
Species:  Human
Tissue:  RBL cells.
Response measured:  Stimulation of IP accumulation.
References:  88
Effect on growth of human ovarian cancer cells.
Species:  Human
Tissue:  A2780, Acis2780, Ovcar-3 or SKOV-3 cells.
Response measured:  Inhibition of cell growth.
References:  26
Effect on cell migration of ovarian cancer cells.
Species:  Human
Tissue:  ES-2 cells.
Response measured:  Cell migration.
References:  91
cAMP production
Species:  Mouse
Tissue:  L-beta-T2 gonadotrope cells
Response measured:  Activation
References:  93
hERG potassium channel
Species:  Mouse
Tissue:  Gonadotrophs
Response measured:  Inhibition
References:  35
Inhibition of LH release from primary rat pituitary cells
Species:  Rat
Tissue:  Pituitary cells
Response measured:  LH release
References:  72
Inhibition of breast cancer cell proliferation
Species:  Human
Tissue:  Human breast cancer cell lines (T47D and SKBR3)
Response measured:  Cell number/proliferation
References:  81
Inhibition of ovarian cancer cell proliferation
Species:  Human
Tissue:  Human ovarian cancer cell lines (OVCAR3 and CAOV4)
Response measured:  Cell number/proliferation
References:  81
Effect on cardiomyocyte contraction
Species:  Mouse
Tissue:  Heart (cardiomyocytes)
Response measured:  Cardiomyocyte contraction
References:  24
Ca2+ release in cardiomyocytes
Species:  Mouse
Tissue:  Heart (cardiomyocytes)
Response measured:  Ca2+ release
References:  24
Effect on growth of human endometrial cancer cells.
Species:  Human
Tissue:  Hec1A, Ishikawa and OAW-42 cells.
Response measured:  Inhibition of cell growth.
References:  26
Impedance-based real-time measurement of cell morphology.
Species:  Human
Tissue:  CHOhGnRH cells
Response measured:  Changes in impedance induced by changes in cell morphology.
References:  66
Impedance-based real-time measurement of cell morphology.
Species:  Mouse
Tissue:  αT3-1 cells
Response measured:  Changes in impedance induced by changes in cell morphology.
References:  66
Effect on cell migration or cell invasion of endometrial cancer cells.
Species:  Human
Tissue:  Ishikawa or ECC-1 cells.
Response measured:  Cell migration or invasion.
References:  96
Physiological Functions Click here for help
Gonadotropin synthesis and secretion.
Species:  Human
Tissue:  Pituitary.
References:  14
Ovarian steroidogenesis.
Species:  Human
Tissue:  Ovary.
References:  14
Cell proliferation.
Species:  Human
Tissue:  Malignant tumours.
References:  14
Apoptosis.
Species:  Human
Tissue:  Ovarian granulosa cells.
References:  14
Physiological Consequences of Altering Gene Expression Click here for help
Mutant mice with inactive GnRH receptors exhibit a deficiency in LH, follicle-stimulating hormone and gonadal steroids. In addition, there is failure of the sex organs to develop postnatally, resulting in small, undescended testes that are located in the low abdominal position as well as poor differentiation of Leydig cells.
Species:  Mouse
Tissue: 
Technique:  Induced mutation.
References:  57,71
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0005189 abnormal anogenital distance PMID: 15625238 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0005418 abnormal circulating hormone level PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0009199 abnormal external male genitalia morphology PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0001119 abnormal female reproductive system morphology PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0003699 abnormal female reproductive system physiology PMID: 20068010 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0009209 abnormal internal female genitalia morphology PMID: 20068010 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0009205 abnormal internal male genitalia morphology PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0001145 abnormal male reproductive system morphology PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0001126 abnormal ovary morphology PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0009363 abnormal secondary ovarian follicle morphology PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0002216 abnormal seminiferous tubule morphology PMID: 20068010 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0006379 abnormal spermatocyte morphology PMID: 20068010 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0001146 abnormal testis morphology PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0001134 absent corpus luteum PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0009009 absent estrous cycle PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0008261 arrest of male meiosis PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0001143 constricted vagina opening PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0002286 cryptorchism PMID: 15625238 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0003510 decreased circulating dihydrotestosterone level PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0005181 decreased circulating estradiol level PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0002790 decreased circulating follicle stimulating hormone level PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0002790 decreased circulating follicle stimulating hormone level PMID: 20068010 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0002773 decreased circulating luteinizing hormone level PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0005185 decreased circulating progesterone level PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0005185 decreased circulating progesterone level PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0002780 decreased circulating testosterone level PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0002780 decreased circulating testosterone level PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0005130 decreased follicle stimulating hormone level PMID: 15625238 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0005132 decreased luteinizing hormone level PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0004856 decreased ovary weight PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0004852 decreased testis weight PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0004852 decreased testis weight PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0002636 delayed vaginal opening PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0002636 delayed vaginal opening PMID: 20068010 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0001926 female infertility PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0001129 impaired ovarian folliculogenesis PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0001129 impaired ovarian folliculogenesis PMID: 20068010 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0001260 increased body weight PMID: 20068010 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0001925 male infertility PMID: 20068010 
Gnrhrtm1(cre)Uboe Gnrhrtm1(cre)Uboe/?
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0002169 no abnormal phenotype detected PMID: 18325995 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0004930 small epididymis PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0004930 small epididymis PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0001116 small gonad PMID: 15625238 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0001127 small ovary PMID: 15625238 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0005188 small penis PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0005188 small penis PMID: 20068010 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0002716 small preputial glands PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0001157 small seminal vesicle PMID: 15625238 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0001157 small seminal vesicle PMID: 20068010 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0001153 small seminiferous tubules PMID: 20068010 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0001147 small testis PMID: 20068010 
GnrhrGt(CMHD-GT_181A6-3)Cmhd GnrhrGt(CMHD-GT_181A6-3)Cmhd/GnrhrGt(CMHD-GT_181A6-3)Cmhd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:95790  MP:0009081 thin uterus PMID: 20068010 
Gnrhrhh Gnrhrhh/Gnrhrhh
involves: 129S6/SvEvTac * C57BL/6		 MGI:95790  MP:0001121 uterus hypoplasia PMID: 15625238 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Fertile eunuch syndrome
OMIM: 228300
Orphanet: ORPHA432
Disease:  Hypogonadotropic hypogonadism 7 with or without anosmia; HH7
Synonyms: Idiopathic hypogonadotropic hypogonadism
Isolated hypogonadotropic hypogonadism
OMIM: 146110
Orphanet: ORPHA432
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human N10K 15
Missense Human T32I 15
Missense Human Q106R 15
Missense Human A129D 15
Missense Human A171T 15
Missense Human C200Y 15
Missense Human R262Q 15
Missense Human L266R 15
Missense Human Y284C 15
Disease:  Normosmic congenital hypogonadotropic hypogonadism
Orphanet: ORPHA432
Comments:  A number of inactivating single nucleotide polymorphisms have been identified in the human GnRH receptor gene, resulting in complete loss of ligand binding, receptor-mediated signalling or reduced receptor expression. Defects in GnRHR are a cause of hypogonadotropic hypogonadism (HH).
References:  11
Clinically-Relevant Mutations and Pathophysiology Comments
Many more somatic mutations have been described. It remains a challenge to link the severity of the gonadotropic deficiency to the genotype.
General Comments
The mammalian GnRH receptor is the only GPCR in which the intracellular C-terminal tail is completely absent. Unlike other GPCRs, it does not show rapid desensitisation of IP production and the rate of internalisation is low. The addition of a functional intracellular C-terminal tail to the receptor produces rapid desinsitisation and increases internalisation rates [32].

For a review on GnRH and the GnRH receptor see [21,59].

References

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