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RXFP2

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Target not currently curated in GtoImmuPdb

Target id: 352

Nomenclature: RXFP2

Family: Relaxin family peptide 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 7 754 13q13.1 RXFP2 relaxin family peptide receptor 2 26
Mouse 7 737 5 89.23 cM Rxfp2 relaxin/insulin-like family peptide receptor 2 32
Rat 7 737 12p12 Rxfp2 relaxin family peptide receptor 2 33
Previous and Unofficial Names Click here for help
GPR106 | RXFPR2 | relaxin receptor 2 | INSL3 receptor | leucine-rich repeat-containing G protein-coupled receptor 8 | LGR8 | relaxin/insulin like family peptide receptor 2
Database Links Click here for help
Specialist databases
GPCRdb rxfp2_human (Hs), rxfp2_mouse (Mm), q5ecl0_rat (Rn)
Other databases
Alphafold Q8WXD0 (Hs), Q91ZZ5 (Mm), Q5ECL0 (Rn)
CATH/Gene3D 3.80.10.10
ChEMBL Target CHEMBL1628482 (Hs), CHEMBL3714702 (Mm)
Ensembl Gene ENSG00000133105 (Hs), ENSMUSG00000053368 (Mm), ENSRNOG00000000897 (Rn)
Entrez Gene 122042 (Hs), 140498 (Mm), 363866 (Rn)
Human Protein Atlas ENSG00000133105 (Hs)
KEGG Gene hsa:122042 (Hs), mmu:140498 (Mm), rno:363866 (Rn)
OMIM 606655 (Hs)
Pharos Q8WXD0 (Hs)
RefSeq Nucleotide NM_130806 (Hs), NM_080468 (Mm), NM_001012475 (Rn)
RefSeq Protein NP_570718 (Hs), NP_536716 (Mm), NP_001012493 (Rn)
UniProtKB Q8WXD0 (Hs), Q91ZZ5 (Mm), Q5ECL0 (Rn)
Wikipedia RXFP2 (Hs)
Natural/Endogenous Ligands Click here for help
INSL3 {Sp: Human}
relaxin-1 {Sp: Human}
relaxin {Sp: Human}
relaxin-3 {Sp: Human}
Comments: INSL3 is the most potent endogenous agonist. Although human relaxin and relaxin-1 have high affinity for RXFP2 they are unlikely to interact with the receptor physiologically.
Potency order of endogenous ligands (Human)
INSL3 (INSL3, P51460) > relaxin (RLN2, P04090) >> relaxin-3 (RLN3, Q8WXF3)  [30,38]

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
INSL3 {Sp: Human} Peptide Click here for species-specific activity table Hs Full agonist 10.4 pKd 24
⤷ pKd 10.4 [24]
[125I]INSL3 (human) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 10.0 pKd 31
⤷ pKd 10.0 [31]
[33P]relaxin (human) Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 9.0 – 9.2 pKd 19,38
⤷ pKd 9.0 – 9.2 (Kd 1.06x10-9 – 6.3x10-10 M) [19,38]
europium-labelled INSL3 Peptide Ligand is labelled Hs Full agonist 9.0 pKd 35
⤷ pKd 9.0 (Kd 9x10-10 M) [35]
NanoLuc-INSL3 Peptide Ligand is labelled Hs Agonist 8.7 pKd 41
⤷ pKd 8.7 (Kd 2x10-9 M) [41]
Description: Receptor binding affinity
INSL3 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 9.3 – 9.7 pKi 19,24
⤷ pKi 9.3 – 9.7 [19,24]
relaxin-1 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.8 pKi 3
⤷ pKi 8.8 [3]
relaxin {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.3 – 8.5 pKi 19,24
⤷ pKi 8.3 – 8.5 [19,24]
relaxin {Sp: Pig} Peptide Click here for species-specific activity table Hs Full agonist 7.9 pKi 19
⤷ pKi 7.9 [19]
relaxin {Sp: Rhesus macaque} Peptide Click here for species-specific activity table Hs Full agonist 7.8 pKi 19
⤷ pKi 7.8 [19]
INSL3 [A(5-26):B(7-27)] Peptide Hs Agonist 7.8 pKi 4
⤷ pKi 7.8 (Ki 1.6x10-8 M) [4]
Description: Receptor binding
relaxin-3 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 7.0 pKi 3
⤷ pKi 7.0 [3]
INSL3 [A(5-26):B(7-27)] Peptide Hs Agonist 10.0 pEC50 4
⤷ pEC50 10.0 (EC50 1x10-10 M) [4]
Description: Receptor activation
relaxin {Sp: Human} Peptide Click here for species-specific activity table Hs Full agonist 9.1 pEC50 24
⤷ pEC50 9.1 [24]
compound 6641 Small molecule or natural product Hs Agonist 6.4 pEC50 12
⤷ pEC50 6.4 (EC50 3.8x10-7 M) [12]
Description: Determined in a HTRF cAMP assay using HEK-RXFP2 cells.
TamRLX Peptide Click here for species-specific activity table Ligand is labelled Hs Agonist - - 22
⤷ [22]
Agonist Comments
Affinity values were determined in HEK 293 cells expressing human RXFP2.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
A(9-26)INSL3 Peptide Hs Antagonist 9.1 pKi 24
⤷ pKi 9.1 [24]
A(10-24)INSL3 Peptide Hs Antagonist 8.7 pKi 24
⤷ pKi 8.7 [24]
A(C10/15S)INSL3 Peptide Hs Antagonist 8.6 pKi 42
⤷ pKi 8.6 [42]
INSL3 B chain dimer analogue 8 Peptide Hs Antagonist 8.5 pKi 36
⤷ pKi 8.5 [36]
A(Δ10/15C)INSL3 Peptide Hs Antagonist 8.3 pKi 42
⤷ pKi 8.3 [42]
cyclic INSL3 B-chain analogue 6 Peptide Hs Antagonist 6.7 pKi 34
⤷ pKi 6.7 [34]
A(4-24)(B7-24)H2 Peptide Click here for species-specific activity table Hs Antagonist 6.0 pKi 25
⤷ pKi 6.0 [25]
INSL3 B-chain analogue Peptide Hs Antagonist 5.1 pKi 9
⤷ pKi 5.1 (Ki 7.943x10-6 M) [9]
A(4-24)(B7-24)H2 Peptide Click here for species-specific activity table Hs Antagonist 6.0 pEC50 25
⤷ pEC50 6.0 [25]
(des 1-8) A-chain INSL3 analogue Peptide Hs Antagonist - - 5
⤷ [5]
RLF-(A11-B10)-isopeptide amideA26 (xA11-B10) Peptide Hs Antagonist - - 6
⤷ [6]
Antagonist Comments
There are now quite a large range of high affinity antagonists available for RXFP2 that contrast strongly with the paucity of antagonists for the closely related RXFP1. This informs the different modes of interaction of relaxin and INSL3 with their respective cognate receptors.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family
Gi/Go family 		Adenylyl cyclase stimulation
Adenylyl cyclase inhibition
Comments:  RXFP2 couples to a subset of the pathways activated by RXFP1. RXFP2 couples to Gs and GOB but unlike RXFP1 does not couple to Gi3. In some cell types in vivo receptor activation may decrease cAMP levels.
References:  18-19,26-27,30,38
Tissue Distribution Click here for help
Pituitary, testis, kidney.
Species:  Human
Technique:  RT-PCR.
References:  14
Osteoblasts
Species:  Human
Technique:  RT-PCR
References:  13
Prostate
Species:  Human
Technique:  RT-PCR
References:  28
Thyroid.
Species:  Human
Technique:  RT-PCR.
References:  23
Testis, uterus, brain, kidney, thyroid, muscle, peripheral blood cell, bone marrow.
Species:  Human
Technique:  RT-PCR.
References:  26
Bladder.
Species:  Human
Technique:  RT-PCR
References:  10
Skeletal muscle
Species:  Mouse
Technique:  RT-PCR
References:  7
Gubernaculum, testis and brain.
Species:  Mouse
Technique:  RT-PCR.
References:  32
Gubernaculum.
Species:  Rat
Technique:  Northern blot.
References:  30
Kidney.
Species:  Rat
Technique:  RT-PCR, in situ hybridisation.
References:  15
Thalamus.
Species:  Rat
Technique:  RT-PCR, in situ hybridisation.
References:  37
Testis, ovary.
Species:  Rat
Technique:  Northern blot, in situ hybridisation.
References:  27
Gubernaculum, testis.
Species:  Rat
Technique:  RT-PCR.
References:  2,29
Ovary; thecal cells
Species:  Bovine
Technique:  RT-PCR
References:  16
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 cAMP levels in HEK 293T cells transfected with RXFP2 receptors.
Species:  Human
Tissue:  HEK 293T cells.
Response measured:  cAMP accumulation.
References:  18-19,26,30,38
Growth of organ cultures of day 17 fetal rat gubernaculum.
Species:  Rat
Tissue:  Fetal gubernaculum.
Response measured:  Growth by BrdU incorporation.
References:  29
Measurement of cAMP levels in cultured gubernacular cells.
Species:  Rat
Tissue:  Gubernaculum.
Response measured:  cAMP accumulation.
References:  30
Responses in mature myotubes differentiated from C2C12 cells
Species:  Mouse
Tissue:  Mature myotubes differentiated from C2C12 cells
Response measured:  AKT/mTOR/S6 phosphorylation
References:  7
Real time measurement of cAMP levels in HEK 293T cells transfected with RXFP2 receptors.
Species:  Human
Tissue:  HEK 293T cells.
Response measured:  Bret based CAMYEL (cAMP sensor using YFP-Epac-Rluc)
References:  39
Responses in bone and osteoblasts
Species:  Human
Tissue:  Bone biopsies, osteoblast cell line, primary osteoblast cultures
Response measured:  cAMP accumulation, pERK1/2 activation, proliferation, mineralisation, alterations in specific osteoblast gene expression
References:  13
Physiological Functions Click here for help
Oocyte maturation.
Species:  Rat
Tissue:  Oocyte.
References:  27
Male germ cell survival.
Species:  Rat
Tissue:  Male germ cells.
References:  27
Mediates the transabdominal phase of testicular descent.
Species:  Mouse
Tissue:  Gubernaculum.
References:  11,17
Bone formation and maintenance
Species:  Human
Tissue:  Bone-anabolic and bone maintenance
References:  7,13
Androgen production in thecal cells
Species:  Bovine
Tissue:  Thecal cells
References:  16
Preantral follicle growth
Species:  Rat
Tissue:  Ovary.
References:  11,40
Knee laxity related to regulation of RXFP1 and RXFP2 by female and male sex-steroids.
Species:  Rat
Tissue:  Patella tendon and lateral collateral ligament.
References:  8
Maintenance of bone and skeletal muscle
Species:  Mouse
Tissue:  Bone density, osteoblast maturation, skeletal muscle strength.
References:  11
Corneal wound healing.
Species:  Mouse
Tissue:  Cornea, increased MMP and TIMP expression and wound healing.
References:  20
Role in skeletal muscle metabolism and function.
Species:  Mouse
Tissue: 
References:  7
Physiological Consequences of Altering Gene Expression Click here for help
RXFP2 knockout mice develop osteoporosis
Species:  Mouse
Tissue:  Bone
Technique:  Gene knockouts
References:  13
Male mice lacking the RXFP2 receptor demonstrate cryptorchidism due to the failure of the gubernaculum to develop.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  17
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
Rxfp2tm1Aia Rxfp2tm1Aia/Rxfp2tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J		 MGI:2153463  MP:0005149 abnormal gubernaculum morphology PMID: 12217959 
crsp|Rxfp2+|Rxfp2tm1Aia Rxfp2tm1Aia/crsp
involves: 129S7/SvEvBrd * C57BL/6J * FVB/N		 MGI:1313307  MGI:2153463  MP:0005149 abnormal gubernaculum morphology PMID: 12217959 
Rxfp2tm1Aia Rxfp2tm1Aia/Rxfp2tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J		 MGI:2153463  MP:0003673 abnormal inguinal canal morphology PMID: 12217959 
Rxfp1tm1Aia|Rxfp2tm1Aia Rxfp1tm1Aia/Rxfp1tm1Aia,Rxfp2tm1Aia/Rxfp2tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J		 MGI:2153463  MGI:2682211  MP:0001882 abnormal lactation PMID: 15256493 
Rxfp1tm1Aia|Rxfp2tm1Aia Rxfp1tm1Aia/Rxfp1tm1Aia,Rxfp2tm1Aia/Rxfp2tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J		 MGI:2153463  MGI:2682211  MP:0006078 abnormal nipple morphology PMID: 15256493 
crsp|Rxfp2+|Rxfp2tm1Aia Rxfp2tm1Aia/crsp
involves: 129S7/SvEvBrd * C57BL/6J * FVB/N		 MGI:1313307  MGI:2153463  MP:0009213 absent male inguinal canal PMID: 12217959 
Rxfp2tm1Aia Rxfp2tm1Aia/Rxfp2tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J		 MGI:2153463  MP:0001155 arrest of spermatogenesis PMID: 12217959 
crsp|Rxfp2+|Rxfp2tm1Aia Rxfp2tm1Aia/crsp
involves: 129S7/SvEvBrd * C57BL/6J * FVB/N		 MGI:1313307  MGI:2153463  MP:0001155 arrest of spermatogenesis PMID: 12217959 
Rxfp2tm1Aia Rxfp2tm1Aia/Rxfp2tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J		 MGI:2153463  MP:0005159 azoospermia PMID: 12217959 
crsp|Rxfp2+|Rxfp2tm1Aia Rxfp2tm1Aia/crsp
involves: 129S7/SvEvBrd * C57BL/6J * FVB/N		 MGI:1313307  MGI:2153463  MP:0005159 azoospermia PMID: 12217959 
Rxfp2tm1Aia Rxfp2tm1Aia/Rxfp2tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J		 MGI:2153463  MP:0002286 cryptorchism PMID: 12217959 
Rxfp1tm1Aia|Rxfp2tm1Aia Rxfp1tm1Aia/Rxfp1tm1Aia,Rxfp2tm1Aia/Rxfp2tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J		 MGI:2153463  MGI:2682211  MP:0002286 cryptorchism PMID: 15256493 
crsp|Rxfp2+|Rxfp2tm1Aia Rxfp2tm1Aia/crsp
involves: 129S7/SvEvBrd * C57BL/6J * FVB/N		 MGI:1313307  MGI:2153463  MP:0002286 cryptorchism PMID: 12217959 
Rxfp2tm1Aia Rxfp2tm1Aia/Rxfp2tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J		 MGI:2153463  MP:0001925 male infertility PMID: 12217959 
crsp|Rxfp2+|Rxfp2tm1Aia Rxfp2tm1Aia/crsp
involves: 129S7/SvEvBrd * C57BL/6J * FVB/N		 MGI:1313307  MGI:2153463  MP:0001925 male infertility PMID: 12217959 
Rxfp2tm1Aia Rxfp2tm1Aia/Rxfp2tm1Aia
involves: 129S7/SvEvBrd * C57BL/6J		 MGI:2153463  MP:0001147 small testis PMID: 12217959 
crsp|Rxfp2+|Rxfp2tm1Aia Rxfp2tm1Aia/crsp
involves: 129S7/SvEvBrd * C57BL/6J * FVB/N		 MGI:1313307  MGI:2153463  MP:0001147 small testis PMID: 12217959 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Cryptorchidism
Disease Ontology: DOID:11383
Role:  Boys with homozygous missense loss of function variant in RXFP2 all show cryptorchidism
References:  1
Disease:  Cryptorchidism
Disease Ontology: DOID:11383
References:  21
Disease:  Osteoporosis
Disease Ontology: DOID:11476
OMIM: 166710
Role:  Men with the T222P mutation of RXFP2 show a markedly increased susceptibility to osteoporosis a condition that is also displayed by RXFP2 knockout mice
References:  13

References

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1. Ayers K, Kumar R, Robevska G, Bruell S, Bell K, Malik MA, Bathgate RA, Sinclair A. (2019) Familial bilateral cryptorchidism is caused by recessive variants in RXFP2. J Med Genet, 56 (11): 727-733. [PMID:31167797]

2. Barthold JS, Robbins A, Wang Y, Pugarelli J, Mateson A, Anand-Ivell R, Ivell R, McCahan SM, Akins Jr RE. (2014) Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling. Biol Reprod, 91 (2): 41. [PMID:24966393]

3. Bathgate RA, Lin F, Hanson NF, Otvos L, Guidolin A, Giannakis C, Bastiras S, Layfield SL, Ferraro T, Ma S, Zhao C, Gundlach AL, Samuel CS, Tregear GW, Wade JD. (2006) Relaxin-3: Improved Synthesis Strategy and Demonstration of Its High-Affinity Interaction with the Relaxin Receptor LGR7 Both In Vitro and In Vivo. Biochemistry, 45: 1043-1053. [PMID:16411781]

4. Bathgate RA, Zhang S, Hughes RA, Rosengren KJ, Wade JD. (2012) The structural determinants of insulin-like Peptide 3 activity. Front Endocrinol (Lausanne), 3: 11. [PMID:22654853]

5. Büllesbach EE, Schwabe C. (2005) LGR8 signal activation by the relaxin-like factor. J Biol Chem, 280 (15): 14586-90. [PMID:15708846]

6. Büllesbach EE, Schwabe C. (2012) Replacement of disulfides by amide bonds in the relaxin-like factor (RLF/INSL3) reveals a role for the A11-B10 link in transmembrane signaling. Biochemistry, 51 (20): 4198-205. [PMID:22574850]

7. De Toni L, Agoulnik AI, Sandri M, Foresta C, Ferlin A. (2019) INSL3 in the muscolo-skeletal system. Mol Cell Endocrinol, 487: 12-17. [PMID:30625346]

8. Dehghan F, Muniandy S, Yusof A, Salleh N. (2014) Sex-steroid regulation of relaxin receptor isoforms (RXFP1 & RXFP2) expression in the patellar tendon and lateral collateral ligament of female WKY rats. Int J Med Sci, 11 (2): 180-91. [PMID:24465164]

9. Del Borgo MP, Hughes RA, Bathgate RA, Lin F, Kawamura K, Wade JD. (2006) Analogs of insulin-like peptide 3 (INSL3) B-chain are LGR8 antagonists in vitro and in vivo. J Biol Chem,: 727-729. [PMID:16547350]

10. Diaz EC, Briggs M, Wen Y, Zhuang G, Wallace SL, Dobberfuhl AD, Kao CS, Chen BC. (2020) Characterizing relaxin receptor expression and exploring relaxin's effect on tissue remodeling/fibrosis in the human bladder. BMC Urol, 20 (1): 44. [PMID:32321501]

11. Esteban-Lopez M, Agoulnik AI. (2020) Diverse functions of insulin-like 3 peptide. J Endocrinol, 247 (1): R1-R12. [PMID:32813485]

12. Esteban-Lopez M, Wilson KJ, Myhr C, Kaftanovskaya EM, Henderson MJ, Southall NT, Xu X, Wang A, Hu X, Barnaeva E et al.. (2022) Discovery of small molecule agonists of the Relaxin Family Peptide Receptor 2. Commun Biol, 5 (1): 1183. [PMID:36333465]

13. Ferlin A, Pepe A, Gianesello L, Garolla A, Feng S, Facciolli A, Morello R, Agoulnik AI, Foresta C. (2009) New roles for INSL3 in adults. Ann N Y Acad Sci, 1160: 215-8. [PMID:19416191]

14. Foresta C, Ferlin A. (2004) Role of INSL3 and LGR8 in cryptorchidism and testicular functions. Reprod Biomed Online, 9 (3): 294-8. [PMID:15353080]

15. Fu P, Shen PJ, Zhao CX, Scott DJ, Samuel CS, Wade JD, Tregear GW, Bathgate RA, Gundlach AL. (2005) Detection, localization, and action of the INSL3 receptor, LGR8, in rat kidney. Ann N Y Acad Sci, 1041: 516-9. [PMID:15956754]

16. Glister C, Satchell L, Bathgate RA, Wade JD, Dai Y, Ivell R, Anand-Ivell R, Rodgers RJ, Knight PG. (2013) Functional link between bone morphogenetic proteins and insulin-like peptide 3 signaling in modulating ovarian androgen production. Proc Natl Acad Sci USA, 110 (15): E1426-35. [PMID:23530236]

17. Gorlov IP, Kamat A, Bogatcheva NV, Jones E, Lamb DJ, Truong A, Bishop CE, McElreavey K, Agoulnik AI. (2002) Mutations of the GREAT gene cause cryptorchidism. Hum Mol Genet, 11 (19): 2309-18. [PMID:12217959]

18. Halls ML, Bathgate RA, Summers RJ. (2006) Relaxin family peptide receptors RXFP1 and RXFP2 modulate cAMP signaling by distinct mechanisms. Mol Pharmacol, 70 (1): 214-26. [PMID:16569707]

19. Halls ML, Bond CP, Sudo S, Kumagai J, Ferraro T, Layfield S, Bathgate RA, Summers RJ. (2005) Multiple binding sites revealed by interaction of relaxin family peptides with native and chimeric relaxin family peptide receptors 1 and 2 (LGR7 and LGR8). J Pharmacol Exp Ther, 313 (2): 677-87. [PMID:15649866]

20. Hampel U, Klonisch T, Sel S, Schulze U, Garreis F, Seitmann H, Zouboulis CC, Paulsen FP. (2013) Insulin-like factor 3 promotes wound healing at the ocular surface. Endocrinology, 154 (6): 2034-45. [PMID:23539510]

21. Harris RM, Finlayson C, Weiss J, Fisher L, Hurley L, Barrett T, Emge D, Bathgate RA, Agoulnik AI, Jameson JL. (2010) A missense mutation in LRR8 of RXFP2 is associated with cryptorchidism. Mamm Genome, 21 (9-10): 442-9. [PMID:20963592]

22. Hoare BL, Bruell S, Sethi A, Gooley PR, Lew MJ, Hossain MA, Inoue A, Scott DJ, Bathgate RAD. (2019) Multi-Component Mechanism of H2 Relaxin Binding to RXFP1 through NanoBRET Kinetic Analysis. iScience, 11: 93-113. [PMID:30594862]

23. Hombach-Klonisch S, Hoang-Vu C, Kehlen A, Hinze R, Holzhausen HJ, Weber E, Fischer B, Dralle H, Klonisch T. (2003) INSL-3 is expressed in human hyperplastic and neoplastic thyrocytes. Int J Oncol, 22 (5): 993-1001. [PMID:12684664]

24. Hossain MA, Rosengren KJ, Haugaard-Jönsson LM, Zhang S, Layfield S, Ferraro T, Daly NL, Tregear GW, Wade JD, Bathgate RA. (2008) The A-chain of human relaxin family peptides has distinct roles in the binding and activation of the different relaxin family peptide receptors. J Biol Chem, 283 (25): 17287-97. [PMID:18434306]

25. Hossain MA, Rosengren KJ, Samuel CS, Shabanpoor F, Chan LJ, Bathgate RA, Wade JD. (2011) The minimal active structure of human relaxin-2. J Biol Chem, 286 (43): 37555-65. [PMID:21878627]

26. Hsu SY, Nakabayashi K, Nishi S, Kumagai J, Kudo M, Sherwood OD, Hsueh AJ. (2002) Activation of orphan receptors by the hormone relaxin. Science, 295 (5555): 671-4. [PMID:11809971]

27. Kawamura K, Kumagai J, Sudo S, Chun SY, Pisarska M, Morita H, Toppari J, Fu P, Wade JD, Bathgate RA et al.. (2004) Paracrine regulation of mammalian oocyte maturation and male germ cell survival. Proc Natl Acad Sci USA, 101 (19): 7323-8. [PMID:15123806]

28. Klonisch T, Müller-Huesmann H, Riedel M, Kehlen A, Bialek J, Radestock Y, Holzhausen HJ, Steger K, Ludwig M, Weidner W et al.. (2005) INSL3 in the benign hyperplastic and neoplastic human prostate gland. Int J Oncol, 27 (2): 307-15. [PMID:16010410]

29. Kubota Y, Temelcos C, Bathgate RA, Smith KJ, Scott D, Zhao C, Hutson JM. (2002) The role of insulin 3, testosterone, Müllerian inhibiting substance and relaxin in rat gubernacular growth. Mol Hum Reprod, 8 (10): 900-5. [PMID:12356938]

30. Kumagai J, Hsu SY, Matsumi H, Roh JS, Fu P, Wade JD, Bathgate RA, Hsueh AJ. (2002) INSL3/Leydig insulin-like peptide activates the LGR8 receptor important in testis descent. J Biol Chem, 277 (35): 31283-6. [PMID:12114498]

31. Muda M, He C, Martini PG, Ferraro T, Layfield S, Taylor D, Chevrier C, Schweickhardt R, Kelton C, Ryan PL et al.. (2005) Splice variants of the relaxin and INSL3 receptors reveal unanticipated molecular complexity. Mol Hum Reprod, 11 (8): 591-600. [PMID:16051677]

32. Overbeek PA, Gorlov IP, Sutherland RW, Houston JB, Harrison WR, Boettger-Tong HL, Bishop CE, Agoulnik AI. (2001) A transgenic insertion causing cryptorchidism in mice. Genesis, 30 (1): 26-35. [PMID:11353515]

33. Scott DJ, Fu P, Shen PJ, Gundlach A, Layfield S, Riesewijk A, Tomiyama H, Hutson JM, Tregear GW, Bathgate RA. (2005) Characterization of the rat INSL3 receptor. Ann N Y Acad Sci, 1041: 13-6. [PMID:15956681]

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