GPER

Source: Wikipedia, the free encyclopedia.
GPER1
Identifiers
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000164850

ENSMUSG00000053647

UniProt

Q99527

Q8BMP4

RefSeq (mRNA)

NM_001031682
NM_001039966
NM_001098201
NM_001505

NM_029771

RefSeq (protein)

NP_001035055
NP_001091671
NP_001496

NP_084047

Location (UCSC)Chr 7: 1.08 – 1.09 MbChr 5: 139.41 – 139.41 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans is encoded by the GPER gene.[5] GPER binds to and is activated by the female sex hormone estradiol and is responsible for some of the rapid effects that estradiol has on cells.[6]

Discovery

The classical

gene transcription. Since it takes time for genes to be transcribed into RNA and translated into protein, the effects of estrogens binding to these classical estrogen receptors is delayed. However, estrogens are also known to have effects that are too fast to be caused by regulation of gene transcription.[8] In 2005, it was discovered that a member of the G protein-coupled receptor (GPCR) family, GPR30 also binds with high affinity to estradiol and is responsible in part for the rapid non-genomic actions of estradiol. Based on its ability to bind estradiol, GPR30 was renamed as G protein-coupled estrogen receptor (GPER). GPER is localized in the plasma membrane but is predominantly detected in the endoplasmic reticulum.[9][8]

Ligands

GPER binds estradiol with high

Niacin and nicotinamide bind to the receptor in vitro with very low affinity.[15][16] CCL18 has been identified as an endogenous antagonist of the GPER.[17] GPER-selective ligands (that do not bind the classical estrogen receptors) include the agonist G-1[18] and the antagonists G15[19] and G36.[20][6]

Agonists

Antagonists

Unknown

Non-ligand

Function

This protein is a member of the

kidney medulla and developing follicles of the ovary.[22]

Role in cancer

GPER expression has been studied in cancer using immunohistochemical and transcriptomic approaches, and has been detected in: colon, lung, melanoma, pancreatic, breast,[23] ovarian,[24] and testicular cancer.[25]

Many groups have demonstrated that GPER signaling is tumor suppressive in cancers that are not traditionally hormone responsive, including melanoma, pancreatic, lung and colon cancer.[26][27][28][29] Additionally, many groups have demonstrated that GPER activation is also tumor suppressive in cancers that are classically considered sex hormone responsive, including endometrial cancer, ovarian cancer, prostate cancer, and Leydig cell tumors.[30][31][32][33][34] Although GPER signaling was originally thought to be tumor promoting in some breast cancer models,[35] subsequent reports show that GPER signaling inhibits breast cancer.[36][37][38] Consistent with this, recent studies showed that the presence of GPER protein in human breast cancer tissue correlates with longer survival.[39] In summary, many independent groups have demonstrated that GPER activation may be a therapeutically useful mechanism for a wide range of cancer types.

Linnaeus Therapeutics is currently running NCI clinical trial (NCT04130516) using GPER agonist, LNS8801, as monotherapy and in combination with the immune checkpoint inhibitor, pembrolizumab, for the treatment of multiple solid tumor malignancies. Activation of GPER with LNS8801 has demonstrated efficacy in humans in cutaneous melanoma, uveal melanoma, lung cancer, neuroendocrine cancer, colorectal cancer, and other PD-1 inhibitor refractory cancers.[40][41][42]

Role in normal tissues

Reproductive tissue

Estradiol produces

axis.[48]

Cardiovascular effects

GPER is expressed in the blood vessel

17β-estradiol.[49] GPER also regulates components of the renin–angiotensin system, which also controls blood pressure,[50][51] and is required for superoxide-mediated cardiovascular function and aging.[52]

Central nervous system activity

GPER and ERα, but not ERβ, have been found to mediate the

medial preoptic area and medial basal hypothalamus, actions that may be mediated by activation of GPER and/or ERβ.[58] Estradiol, as well as tamoxifen and fulvestrant, have been found to rapidly induce lordosis through activation of GPER in the arcuate nucleus of the hypothalamus of female rats.[59][60]

Metabolic roles

Female GPER

trabecular bone volume, and persistent growth plate activity resulting in longer bones.[62][63] The GPER-selective agonist G-1 shows therapeutic efficacy in mouse models of obesity and diabetes.[64]

Role in neurological disorders

GPER is broadly expressed on the nervous system, and GPER activation promotes beneficial effects in several brain disorders.[65] A study suggests that GPER levels were significantly lower in children with ADHD compared to controls.[66]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164850 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000053647 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. PMID 9479505
    .
  6. ^
    PMID 26023144
    .
  7. S2CID 196618575
    .
  8. ^
    PMID 25351351
    .
  9. ^
    S2CID 15789136
    .
  10. S2CID 33801811
    .
  11. S2CID 27712910
    .
  12. PMID 17222505
    .
  13. S2CID 28968323
    .
  14. S2CID 28896943
    .
  15. PMID 24662263
    . Nicotinic acid, also known as niacin, is the water soluble vitamin B3 used for decades for the treatment of dyslipidemic diseases. Its action is mainly mediated by the G protein-coupled receptor (GPR) 109A; however, certain regulatory effects on lipid levels occur in a GPR109A-independent manner. The amide form of nicotinic acid, named nicotinamide, acts as a vitamin although neither activates the GPR109A nor exhibits the pharmacological properties of nicotinic acid. In the present study, we demonstrate for the first time that nicotinic acid and nicotinamide bind to and activate the GPER-mediated signalling in breast cancer cells and cancer-associated fibroblasts (CAFs)
  16. PMID 26921679
    .
  17. S2CID 24889239
    .
  18. S2CID 2364534
    .
  19. PMID 19430488
    .
  20. PMID 21782022
    .
  21. ^ "Entrez Gene: GPR30 G protein-coupled receptor 30".
  22. PMID 19420011
    .
  23. S2CID 10593826
    .
  24. PMID 19501895
    .
  25. PMID 22496838
    .
  26. PMID 27082459
    .
  27. PMID 28476123
    .
  28. PMID 28467693
    .
  29. doi:10.7554/elife.31770.017. {{cite journal}}: Cite journal requires |journal= (help
    )
  30. PMID 23849542
    .
  31. PMID 25287069
    .
  32. PMID 23921077
    .
  33. PMID 23907461
    .
  34. doi:10.1101/365668
    . Retrieved 8 April 2024.
  35. PMID 24834064
    .
  36. PMID 25275589
    .
  37. PMID 24515910
    .
  38. PMID 24553912
    .
  39. PMID 29899833
    .
  40. ISSN 0732-183X
    .
  41. ISSN 0923-7534
    .
  42. doi:10.1136/jitc-2022-sitc2022.0759
    .
  43. ^
    PMID 24718936
    .
  44. PMID 24834064
    .
  45. PMID 22139333
    .
  46. PMID 21703280
    .
  47. PMID 22440937
    .
  48. ^
    PMID 24474947
    .
  49. PMID 22203741
    . The development of the GPER-selective agonist G-114 has facilitated studies that demonstrate GPER activation induces acute vasodilation and lowers blood pressure in rodents. We18 and others17,19 have shown that acute GPER-mediated vasodilator effects are at least partly endothelium- and NO-dependent.
  50. PMID 22153880
    .
  51. PMID 23466742
    .
  52. PMID 27803283
    .
  53. S2CID 205595404
    .
  54. PMID 19430488
    .
  55. ^
    PMID 19095043
    .
  56. PMID 22143579
    .
  57. ^
    ISBN 978-0-521-19035-0
    .
  58. ^
    ISBN 978-0-387-30362-8
    .
  59. PMID 25245158
    .
  60. PMID 28063803
    .
  61. PMID 18845638
    .
  62. PMID 20734455
    .
  63. PMID 23970785
    .
  64. PMID 31996464
    .
  65. S2CID 202043731
    .
  66. PMID 29659348
    .

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Retrieved from "https://en.wikipedia.org/w/index.php?title=GPER&oldid=1223296445"
This page is based on the copyrighted Wikipedia article: GPER. Articles is available under the CC BY-SA 3.0 license; additional terms may apply.Privacy Policy