LH receptor
Target not currently curated in GtoImmuPdb
Target id: 254
Nomenclature: LH receptor
Family: Glycoprotein hormone receptors
Annotation status:
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Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Natural/Endogenous Ligands
- Rank order lists
- Agonists
- Antagonists
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Biologically Significant Variants
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 699 | 2p21 | LHCGR | luteinizing hormone/choriogonadotropin receptor | 14 |
| Mouse | 7 | 700 | 17 E4 | Lhcgr | luteinizing hormone/choriogonadotropin receptor | 8 |
| Rat | 7 | 700 | 6q12 | Lhcgr | luteinizing hormone/choriogonadotropin receptor | 13 |
| Previous and Unofficial Names |
| Choriogonadotropin receptor | LCGR | LGR2 | LHR | lutropin-choriogonadotropic hormone receptor | LH-R |
| Database Links |
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| Specialist databases | |
| GPCRDB | lshr_human (Hs), lshr_mouse (Mm), lshr_rat (Rn) |
| Other databases | |
| CATH/Gene3D | 3.80.10.10 |
| ChEMBL Target | CHEMBL1854 (Hs), CHEMBL2456 (Rn) |
| DrugBank Target | P22888 (Hs) |
| Ensembl Gene | ENSG00000138039 (Hs), ENSMUSG00000024107 (Mm), ENSRNOG00000016712 (Rn) |
| Entrez Gene | 3973 (Hs), 16867 (Mm), 25477 (Rn) |
| Human Protein Atlas | ENSG00000138039 (Hs) |
| KEGG Gene | hsa:3973 (Hs), mmu:16867 (Mm), rno:25477 (Rn) |
| OMIM | 152790 (Hs) |
| Orphanet | ORPHA123048 (Hs) |
| Pharos | P22888 (Hs) |
| RefSeq Nucleotide | NM_000233 (Hs), NM_013582 (Mm), NM_012978 (Rn) |
| RefSeq Protein | NP_000224 (Hs), NP_038610 (Mm), NP_037110 (Rn) |
| UniProtKB | P22888 (Hs), P30730 (Mm), P16235 (Rn) |
| Wikipedia | LHCGR (Hs) |
| Natural/Endogenous Ligands |
| hCG {Sp: Human} |
| LH {Sp: Human} , LH {Sp: Mouse} , LH {Sp: Rat} |
| Potency order of endogenous ligands |
| LH (LHB, CGA, P01229, P01215), hCG (CGA, CGB3, P01233, P01215) [9,15] |
Download all structure-activity data for this target as a CSV file 
| Agonists | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Various thienopyrimidine derivatives are known LH receptor agonists binding with pIC50 values of between 7.7 and 5 [18]. There are considerable differences in affinity when comparing various species combinations of receptors and the natural ligands [6]. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonist Comments | ||
| Deglycosylated hCGs (human chorionic gonadotropins) are known LH receptor antagonists [3,12]. |
| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gs family | Adenylate cyclase stimulation |
| References: 7,10 | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
| Gq/G11 family | Phospholipase C stimulation |
| Comments: At high receptor and/or agonist concentrations, Gq/11 is stimulated. | |
| References: 5,10 | |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| In many tissues mRNA expression, protein expression and even receptor activity has been found. It is however still under debate whether such functional expression has physiological relevance, since the human and mouse knockouts do not show deficiencies related to this extragonadal expression. | ||||||||
| Expression Datasets |
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| Functional Assays
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| Physiological Functions
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| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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References
1. Bambino TH, Hsueh AJ. (1981) Direct inhibitory effect of glucocorticoids upon testicular luteinizing hormone receptor and steroidogenesis in vivo and in vitro. Endocrinology, 108 (6): 2142-8. [PMID:6262050]
2. Bukovsky A, Indrapichate K, Fujiwara H, Cekanova M, Ayala ME, Dominguez R, Caudle MR, Wimalsena J, Elder RF, Copas P et al.. (2003) Multiple luteinizing hormone receptor (LHR) protein variants, interspecies reactivity of anti-LHR mAb clone 3B5, subcellular localization of LHR in human placenta, pelvic floor and brain, and possible role for LHR in the development of abnormal pregnancy, pelvic floor disorders and Alzheimer's disease. Reprod. Biol. Endocrinol., 1: 46. [PMID:12816543]
3. Channing CP, Sakai CN, Bahl OP. (1978) Role of the carbohydrate residues of human chorionic gonadotropin in binding and stimulation of adenosine 3',5'-monophosphate accumulation by porcine granulosa cells. Endocrinology, 103 (2): 341-8. [PMID:217642]
4. Dirnhofer S, Berger C, Hermann M, Steiner G, Madersbacher S, Berger P. (1998) Coexpression of gonadotropic hormones and their corresponding FSH- and LH/CG-receptors in the human prostate. Prostate, 35 (3): 212-20. [PMID:9582090]
5. Donadeu FX, Ascoli M. (2005) The differential effects of the gonadotropin receptors on aromatase expression in primary cultures of immature rat granulosa cells are highly dependent on the density of receptors expressed and the activation of the inositol phosphate cascade. Endocrinology, 146 (9): 3907-16. [PMID:15919743]
6. Galet C, Ascoli M. (2005) The differential binding affinities of the luteinizing hormone (LH)/choriogonadotropin receptor for LH and choriogonadotropin are dictated by different extracellular domain residues. Mol Endocrinol, 19: 1263-1276. [PMID:15677709]
7. Gilchrist RL, Ryu KS, Ji I, Ji TH. (1996) The luteinizing hormone/chorionic gonadotropin receptor has distinct transmembrane conductors for cAMP and inositol phosphate signals. J. Biol. Chem., 271 (32): 19283-7. [PMID:8702611]
8. Gudermann T, Birnbaumer M, Birnbaumer L. (1992) Evidence for dual coupling of the murine luteinizing hormone receptor to adenylyl cyclase and phosphoinositide breakdown and Ca2+ mobilization. Studies with the cloned murine luteinizing hormone receptor expressed in L cells. J. Biol. Chem., 267 (7): 4479-88. [PMID:1311310]
9. Jia XC, Oikawa M, Bo M, Tanaka T, Ny T, Boime I, Hsueh AJ. (1991) Expression of human luteinizing hormone (LH) receptor: interaction with LH and chorionic gonadotropin from human but not equine, rat, and ovine species. Mol Endocrinol, 5: 759-768. [PMID:1922095]
10. Kühn B, Gudermann T. (1999) The luteinizing hormone receptor activates phospholipase C via preferential coupling to Gi2. Biochemistry, 38 (38): 12490-8. [PMID:10493819]
11. Lei ZM, Mishra S, Zou W, Xu B, Foltz M, Li X, Rao CV. (2001) Targeted disruption of luteinizing hormone/human chorionic gonadotropin receptor gene. Mol. Endocrinol., 15 (1): 184-200. [PMID:11145749]
12. Matzuk MM, Keene JL, Boime I. (1989) Site specificity of the chorionic gonadotropin N-linked oligosaccharides in signal transduction. J. Biol. Chem., 264 (5): 2409-14. [PMID:2536708]
13. McFarland KC, Sprengel R, Phillips HS, Köhler M, Rosemblit N, Nikolics K, Segaloff DL, Seeburg PH. (1989) Lutropin-choriogonadotropin receptor: an unusual member of the G protein-coupled receptor family. Science, 245 (4917): 494-9. [PMID:2502842]
14. Minegishi T, Nakamura K, Takakura Y, Miyamoto K, Hasegawa Y, Ibuki Y, Igarashi M, Minegish T [corrected to Minegishi T]. (1990) Cloning and sequencing of human LH/hCG receptor cDNA. Biochem. Biophys. Res. Commun., 172 (3): 1049-54. [PMID:2244890]
15. Müller T, Gromoll J, Simoni M. (2003) Absence of exon 10 of the human luteinizing hormone (LH) receptor impairs LH, but not human chorionic gonadotropin action. J. Clin. Endocrinol. Metab., 88 (5): 2242-9. [PMID:12727981]
16. Pabon JE, Bird JS, Li X, Huang ZH, Lei ZM, Sanfilippo JS, Yussman MA, Rao CV. (1996) Human skin contains luteinizing hormone/chorionic gonadotropin receptors. J. Clin. Endocrinol. Metab., 81 (7): 2738-41. [PMID:8675605]
17. Pabon JE, Li X, Lei ZM, Sanfilippo JS, Yussman MA, Rao CV. (1996) Novel presence of luteinizing hormone/chorionic gonadotropin receptors in human adrenal glands. J. Clin. Endocrinol. Metab., 81 (6): 2397-400. [PMID:8964884]
18. Palmer SS, Mckenna S, Arkinstall S. (2005) Discovery of new molecules for the future treatment of infertility. Reproductive Biomedicine Online 10 Suppl (Proceedings: Gonadotropins from Basic Research to Clinical Practice; Munich Germany.,: 45-54.
19. Powell BL, Piersma D, Kevenaar ME, van Staveren IL, Themmen AP, Iacopetta BJ, Berns EM. (2003) Luteinizing hormone signaling and breast cancer: polymorphisms and age of onset. J. Clin. Endocrinol. Metab., 88 (4): 1653-7. [PMID:12679452]
20. Risbridger GP, Robertson DM, de Kretser DM. (1982) The effects of chronic human chorionic gonadotropin treatment on Leydig cell function. Endocrinology, 110 (1): 138-45. [PMID:6274616]
21. Rommerts FF, Cooke BA, Van der Kemp JW, van der Molen HJ. (1973) Effect of luteinizing hormone on 3',5'-cyclic AMP and testosterone production in isolated interstitial tissue of rat testis. FEBS Lett, 33: 114-118. [PMID:4352930]
22. Sonoda N, Katabuchi H, Tashiro H, Ohba T, Nishimura R, Minegishi T, Okamura H. (2005) Expression of variant luteinizing hormone/chorionic gonadotropin receptors and degradation of chorionic gonadotropin in human chorionic villous macrophages. Placenta, 26 (4): 298-307. [PMID:15823616]
23. Themmen APN, Huhtaniemi IT. (2000) Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function. Endocr. Rev., 21 (5): 551-83. [PMID:11041448]
24. Van Damme MP, Robertson DM, Diczfalusy E. (1974) An improved in vitro bioassay method for measuring luteinizing hormone (LH) activity using mouse Leydig cell preparations. Acta Endocrinol (Copenh), 77: 655-671. [PMID:4372842]
25. van Straten NC, Schoonus-Gerritsma GG, van Someren RG, Draaijer J, Adang AE, Timmers CM, Hanssen RG, van Boeckel CA. (2002) The first orally active low molecular weight agonists for the LH receptor: thienopyr(im)idines with therapeutic potential for ovulation induction. Chembiochem, 3 (10): 1023-6. [PMID:12362369]
26. Wang C, Hsueh AJ, Erickson GF. (1981) LH stimulation of estrogen secretion by cultured rat granulosa cells. Mol. Cell. Endocrinol., 24 (1): 17-28. [PMID:6799341]
27. Zhang FP, Poutanen M, Wilbertz J, Huhtaniemi I. (2001) Normal prenatal but arrested postnatal sexual development of luteinizing hormone receptor knockout (LuRKO) mice. Mol. Endocrinol., 15 (1): 172-83. [PMID:11145748]
28. Zhang M, Shi H, Segaloff DL, Van Voorhis BJ, Zheng M. (2001) Expression and localization of luteinizing hormone receptor in the female mouse reproductive tract. Biol. Reprod., 64 (1): 179-87. [PMID:11133673]
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