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{{Infobox protein
{{Infobox protein
  |Name= [[GNRHR|Gonadotropin-releasing hormone receptor]]
|Name= [[GNRHR|Gonadotropin-releasing hormone receptor]]
  |Symbol=[[GNRHR]]
|Symbol=[[GNRHR]]
  |AltSymbols=GnRH-R; LRHR;
|AltSymbols=GnRH-R; LRHR;
  |HGNCid=4421
|HGNCid=4421
  |Chromosome=4
|Chromosome=4
  |Arm=q
|Arm=q
  |Band=21.2
|Band=21.2
  |LocusSupplementaryData=
|LocusSupplementaryData=
  |ECnumber=
|ECnumber=
  |OMIM=138850
|OMIM=138850
  |EntrezGene=2798
|EntrezGene=2798
  |RefSeq=NM_000406
|RefSeq=NM_000406
  |UniProt=P30968
|UniProt=P30968
}}
}}
{{infobox protein
{{Infobox protein
| Name = [[GNRHR2|Gonadotropin-releasing hormone (type 2) receptor 2]]
| Name = [[GNRHR2|Gonadotropin-releasing hormone (type 2) receptor 2]]
| caption =
| caption =
Line 33: Line 33:
| LocusSupplementaryData =
| LocusSupplementaryData =
}}
}}
The '''gonadotropin-releasing hormone receptor''' (GNRHR), also known as the [[luteinizing hormone releasing hormone]] receptor ('''LHRHR'''), is a member of the seven-transmembrane, [[G-protein coupled receptor]] (GPCR) family. It is expressed on the surface of [[pituitary]] gonadotrope cells as well as [[lymphocyte]]s, [[breast]], [[ovary]], and [[prostate]].


This receptor is a 60 [[kDa]] [[G protein-coupled receptor]] and resides primarily in the [[pituitary]] and is responsible for eliciting the actions of [[LHRH]] after its release from the [[hypothalamus]].<ref name="pmid16140177">{{cite journal | author = Millar RP | title = GnRHs and GnRH receptors | journal = [[Anim. Reprod. Sci.]] | volume = 88 | issue = 1–2 | pages = 5–28 | year = 2005 | pmid = 16140177 | doi = 10.1016/j.anireprosci.2005.05.032 }}</ref> Upon activation, the LHRHr stimulates [[tyrosine phosphatase]] and elicits the release of LH from the pituitary.
The '''gonadotropin-releasing hormone receptor''' ('''GnRHR'''), also known as the [[luteinizing hormone releasing hormone]] receptor ('''LHRHR'''), is a member of the seven-transmembrane, [[G-protein coupled receptor]] (GPCR) family. It is the receptor of [[gonadotropin-releasing hormone]] (GnRH). The GnRHR is expressed on the surface of [[pituitary]] gonadotrope cells as well as [[lymphocyte]]s, [[breast]], [[ovary]], and [[prostate]].


Evidence exists showing the presence of LHRH and its receptor in extrapituitary tissues as well as a role in progression of some [[cancer]]s.<ref name="pmid15613448">{{cite journal |vauthors=Harrison GS, Wierman ME, Nett TM, Glode LM | title = Gonadotropin-releasing hormone and its receptor in normal and malignant cells | journal = Endocr. Relat. Cancer | volume = 11 | issue = 4 | pages = 725–48 | year = 2004 | pmid = 15613448 | doi = 10.1677/erc.1.00777 }}</ref>
This receptor is a 60 [[kDa]] [[G protein-coupled receptor]] and resides primarily in the [[pituitary]] and is responsible for eliciting the actions of GnRH after its release from the [[hypothalamus]].<ref name="pmid16140177">{{cite journal | author = Millar RP | title = GnRHs and GnRH receptors | journal = [[Anim. Reprod. Sci.]] | volume = 88 | issue = 1–2 | pages = 5–28 | year = 2005 | pmid = 16140177 | doi = 10.1016/j.anireprosci.2005.05.032 }}</ref> Upon activation, the LHRHr stimulates [[tyrosine phosphatase]] and elicits the release of LH from the pituitary.


== Function ==
Evidence exists showing the presence of GnRH and its receptor in extrapituitary tissues as well as a role in progression of some [[cancer]]s.<ref name="pmid15613448">{{cite journal |vauthors=Harrison GS, Wierman ME, Nett TM, Glode LM | title = Gonadotropin-releasing hormone and its receptor in normal and malignant cells | journal = Endocr. Relat. Cancer | volume = 11 | issue = 4 | pages = 725–48 | year = 2004 | pmid = 15613448 | doi = 10.1677/erc.1.00777 }}</ref>
Following binding of [[Gonadotropin releasing hormone]] (GNRH), GNRHR associates with G-proteins that activate a [[phosphatidylinositol]] (PtdIns)-[[calcium]] [[second messenger]] system. Activation of GNRHR ultimately causes the release of [[follicle stimulating hormone]] (FSH) and [[luteinizing hormone]] (LH).


== Genes ==
{{TOC limit|3}}
 
==Function==
Following binding of GnRH, the GnRHR associates with G-proteins that activate a [[phosphatidylinositol]] (PtdIns)-[[calcium]] [[second messenger]] system. Activation of the GnRHR ultimately causes the release of [[follicle stimulating hormone]] (FSH) and [[luteinizing hormone]] (LH).
 
==Genes==
There are two major forms of the GNRHR, each encoded by a separate gene (''[[GNRHR]]'' and ''[[GNRHR2]]'').<ref name="pmid15380810">{{cite journal |vauthors=Neill JD, Musgrove LC, Duck LW | title = Newly recognized GnRH receptors: function and relative role | journal = Trends Endocrinol. Metab. | volume = 15 | issue = 8 | pages = 383–92 | year = 2004 | pmid = 15380810 | doi = 10.1016/j.tem.2004.08.005 }}</ref><ref name="pmid15561800">{{cite journal |vauthors=Cheng CK, Leung PC | title = Molecular biology of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and their receptors in humans | journal = Endocr. Rev. | volume = 26 | issue = 2 | pages = 283–306 | year = 2005 | pmid = 15561800 | doi = 10.1210/er.2003-0039 }}</ref>
There are two major forms of the GNRHR, each encoded by a separate gene (''[[GNRHR]]'' and ''[[GNRHR2]]'').<ref name="pmid15380810">{{cite journal |vauthors=Neill JD, Musgrove LC, Duck LW | title = Newly recognized GnRH receptors: function and relative role | journal = Trends Endocrinol. Metab. | volume = 15 | issue = 8 | pages = 383–92 | year = 2004 | pmid = 15380810 | doi = 10.1016/j.tem.2004.08.005 }}</ref><ref name="pmid15561800">{{cite journal |vauthors=Cheng CK, Leung PC | title = Molecular biology of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and their receptors in humans | journal = Endocr. Rev. | volume = 26 | issue = 2 | pages = 283–306 | year = 2005 | pmid = 15561800 | doi = 10.1210/er.2003-0039 }}</ref>


Alternative splicing of the GNRHR gene, ''GNRHR'', results in multiple [[Transcription (genetics)|transcript]] variants encoding different [[isoform]]s. More than 18 [[Transcription (genetics)|transcription]] initiation sites in the 5' region and multiple [[polyA]] signals in the 3' region have been identified for ''GNRHR''.
Alternative splicing of the GNRHR gene, ''GNRHR'', results in multiple [[Transcription (genetics)|transcript]] variants encoding different [[isoform]]s. More than 18 [[Transcription (genetics)|transcription]] initiation sites in the 5' region and multiple [[polyA]] signals in the 3' region have been identified for ''GNRHR''.


== Regulation ==
==Regulation==
The GNRHR responds to GNRH as well as to synthetic [[GNRH agonist]]s. Agonists stimulate the receptor, however prolonged exposure leads to a [[downregulation]] effect resulting in hypogonadism, an effect that is often medically utilized. [[GNRH antagonist]]s block the receptor and inhibit gonadotropin release. GNRHRs are further regulated by the presence of [[sex hormone]]s as well as [[activin and inhibin]].
The GnRHR responds to GnRH as well as to synthetic [[GnRH agonist]]s. Agonists stimulate the receptor, however prolonged exposure leads to a [[downregulation]] effect resulting in hypogonadism, an effect that is often medically utilized. [[GnRH antagonist]]s block the receptor and inhibit gonadotropin release. GnRHRs are further regulated by the presence of [[sex hormone]]s as well as [[activin and inhibin]].
 
==Ligands==
 
===Agonists===


== Clinical implications ==
====Peptides====
* [[Azagly-nafarelin]]
* [[Buserelin]]
* [[Deslorelin]]
* [[Fertirelin]]
* [[Gonadotropin-releasing hormone|GnRH]]
* [[Gonadorelin]]
* [[Goserelin]]
* [[Histrelin]]
* [[Lecirelin]]
* [[Leuprorelin]]
* [[Nafarelin]]
* [[Peforelin]]
* [[Triptorelin]]
 
===Antagonists===
 
====Peptides====
* [[Abarelix]]
* [[Cetrorelix]]
* [[Degarelix]]
* [[Ganirelix]]
* [[Ozarelix]]
 
====Non-peptides====
* [[Elagolix]]
* [[Linzagolix]]
* [[Opigolix]]
* [[Relugolix]]
* [[Sufugolix]]
 
==Clinical implications==
{{Expert needed|Medicine|section|date=March 2011}}
{{Expert needed|Medicine|section|date=March 2011}}
Defects in the ''GNRHR'' are a cause of [[hypogonadotropic hypogonadism]] (HH).<ref name="pmid17543719">{{cite journal | author = Layman LC | title = Hypogonadotropic hypogonadism | journal = Endocrinol. Metab. Clin. North Am. | volume = 36 | issue = 2 | pages = 283–96 | year = 2007 | pmid = 17543719 | doi = 10.1016/j.ecl.2007.03.010 }}</ref>
 
Defects in the GnRHR are a cause of [[hypogonadotropic hypogonadism]] (HH).<ref name="pmid17543719">{{cite journal | author = Layman LC | title = Hypogonadotropic hypogonadism | journal = Endocrinol. Metab. Clin. North Am. | volume = 36 | issue = 2 | pages = 283–96 | year = 2007 | pmid = 17543719 | doi = 10.1016/j.ecl.2007.03.010 }}</ref>


Normal [[puberty]] begins between ages 8 and 14 in girls and between 9 and 14 in boys. Puberty, however, for some children can come much sooner or much later or in many cases never occurs and thereby contributes to the estimated 35-70 million infertile couples worldwide. Among children, the abnormally early or late onset of puberty exerts intense emotional and social stress that too often goes untreated.
Normal [[puberty]] begins between ages 8 and 14 in girls and between 9 and 14 in boys. Puberty, however, for some children can come much sooner or much later or in many cases never occurs and thereby contributes to the estimated 35-70 million infertile couples worldwide. Among children, the abnormally early or late onset of puberty exerts intense emotional and social stress that too often goes untreated.


The timely onset of puberty is regulated by many factors and one factor that is often referred to as the master regulator of puberty and reproduction is the gonadotropin-releasing hormone ([[GnRH]]). GnRH is produced in the hypothalamus but gets secreted and acts upon receptors ([[GNRHR|GnRH-R]]) on the [[anterior pituitary]] to exert its effects on [[sexual maturity|reproductive maturation]].
The timely onset of puberty is regulated by many factors and one factor that is often referred to as the master regulator of puberty and reproduction is GnRH. This peptide hormone is produced in the hypothalamus but gets secreted and acts upon GnRHRs in the [[anterior pituitary]] to exert its effects on [[sexual maturity|reproductive maturation]].


Understanding how GnRH-R functions has been key to developing clinical strategies to treat reproductive-related disorders.<ref name="pmid20628612">{{cite journal | vauthors = Re M, Pampillo M, Savard M, Dubuc C, McArdle CA, Millar RP, Conn PM, Gobeil F, Bhattacharya M, Babwah AV | title = The human gonadotropin releasing hormone type I receptor is a functional intracellular GPCR expressed on the nuclear membrane | journal = PLoS ONE | volume = 5 | issue = 7 | pages = e11489 | year = 2010 | pmid = 20628612 | pmc = 2900216 | doi = 10.1371/journal.pone.0011489 | url = | issn = | editor1-last = Koch | editor1-first = Karl-Wilhelm }}</ref><ref name="pmid20606386">{{cite journal |vauthors=Balasubramanian R, Dwyer A, Seminara SB, Pitteloud N, Kaiser UB, Crowley WF | title = Human GnRH deficiency: a unique disease model to unravel the ontogeny of GnRH neurons | journal = Neuroendocrinology | volume = 92 | issue = 2 | pages = 81–99 | year = 2010 | pmid = 20606386 | doi = 10.1159/000314193 | url = | issn = | pmc=3214927}}</ref><ref name="pmid19944289">{{cite journal |vauthors=Viswanathan V, Eugster EA | title = Etiology and treatment of hypogonadism in adolescents | journal = Endocrinol. Metab. Clin. North Am. | volume = 38 | issue = 4 | pages = 719–38 |date=December 2009 | pmid = 19944289 | doi = 10.1016/j.ecl.2009.08.004 | url = | issn = }}</ref>
Understanding how GnRHR functions has been key to developing clinical strategies to treat reproductive-related disorders.<ref name="pmid20628612">{{cite journal | vauthors = Re M, Pampillo M, Savard M, Dubuc C, McArdle CA, Millar RP, Conn PM, Gobeil F, Bhattacharya M, Babwah AV | title = The human gonadotropin releasing hormone type I receptor is a functional intracellular GPCR expressed on the nuclear membrane | journal = PLoS ONE | volume = 5 | issue = 7 | pages = e11489 | year = 2010 | pmid = 20628612 | pmc = 2900216 | doi = 10.1371/journal.pone.0011489 | url = | issn = | editor1-last = Koch | editor1-first = Karl-Wilhelm }}</ref><ref name="pmid20606386">{{cite journal |vauthors=Balasubramanian R, Dwyer A, Seminara SB, Pitteloud N, Kaiser UB, Crowley WF | title = Human GnRH deficiency: a unique disease model to unravel the ontogeny of GnRH neurons | journal = Neuroendocrinology | volume = 92 | issue = 2 | pages = 81–99 | year = 2010 | pmid = 20606386 | doi = 10.1159/000314193 | url = | issn = | pmc=3214927}}</ref><ref name="pmid19944289">{{cite journal |vauthors=Viswanathan V, Eugster EA | title = Etiology and treatment of hypogonadism in adolescents | journal = Endocrinol. Metab. Clin. North Am. | volume = 38 | issue = 4 | pages = 719–38 |date=December 2009 | pmid = 19944289 | doi = 10.1016/j.ecl.2009.08.004 | url = | issn = | pmc = 4102132 }}</ref>


==See also==
==See also==
* [[GnRH modulator]]
* [[GnRH modulator]]


== References ==
==References==
{{Reflist|2}}
{{Reflist|2}}


Line 69: Line 108:
*{{cite web | url = http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1357 | title = Gonadotrophin-Releasing Hormone Receptors | accessdate = | date = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | archiveurl = | archivedate = }}
*{{cite web | url = http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1357 | title = Gonadotrophin-Releasing Hormone Receptors | accessdate = | date = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | archiveurl = | archivedate = }}
* {{MeshName|GNRHR+protein,+human}}
* {{MeshName|GNRHR+protein,+human}}


{{G protein-coupled receptors}}
{{G protein-coupled receptors}}
{{Neuropeptide receptors}}
{{Neuropeptide receptors}}
{{Peptidergics}}
{{GnRH and gonadotropins}}
{{GnRH and gonadotropin receptor modulators}}


{{DEFAULTSORT:Gonadotropin-Releasing Hormone Receptor}}
{{DEFAULTSORT:Gonadotropin-Releasing Hormone Receptor}}
[[Category:G protein coupled receptors]]
 
[[Category:G protein-coupled receptors]]
[[Category:Gonadotropin-releasing hormone and gonadotropins]]
[[Category:Gonadotropin-releasing hormone and gonadotropins]]

Revision as of 18:00, 24 September 2018

Gonadotropin-releasing hormone receptor
Identifiers
SymbolGNRHR
Alt. symbolsGnRH-R; LRHR;
Entrez2798
HUGO4421
OMIM138850
RefSeqNM_000406
UniProtP30968
Other data
LocusChr. 4 q21.2
Gonadotropin-releasing hormone (type 2) receptor 2
Identifiers
SymbolGNRHR2
Entrez114814
HUGO16341
RefSeqNR_002328
UniProtQ96P88
Other data
LocusChr. 1 q12

The gonadotropin-releasing hormone receptor (GnRHR), also known as the luteinizing hormone releasing hormone receptor (LHRHR), is a member of the seven-transmembrane, G-protein coupled receptor (GPCR) family. It is the receptor of gonadotropin-releasing hormone (GnRH). The GnRHR is expressed on the surface of pituitary gonadotrope cells as well as lymphocytes, breast, ovary, and prostate.

This receptor is a 60 kDa G protein-coupled receptor and resides primarily in the pituitary and is responsible for eliciting the actions of GnRH after its release from the hypothalamus.[1] Upon activation, the LHRHr stimulates tyrosine phosphatase and elicits the release of LH from the pituitary.

Evidence exists showing the presence of GnRH and its receptor in extrapituitary tissues as well as a role in progression of some cancers.[2]

Function

Following binding of GnRH, the GnRHR associates with G-proteins that activate a phosphatidylinositol (PtdIns)-calcium second messenger system. Activation of the GnRHR ultimately causes the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH).

Genes

There are two major forms of the GNRHR, each encoded by a separate gene (GNRHR and GNRHR2).[3][4]

Alternative splicing of the GNRHR gene, GNRHR, results in multiple transcript variants encoding different isoforms. More than 18 transcription initiation sites in the 5' region and multiple polyA signals in the 3' region have been identified for GNRHR.

Regulation

The GnRHR responds to GnRH as well as to synthetic GnRH agonists. Agonists stimulate the receptor, however prolonged exposure leads to a downregulation effect resulting in hypogonadism, an effect that is often medically utilized. GnRH antagonists block the receptor and inhibit gonadotropin release. GnRHRs are further regulated by the presence of sex hormones as well as activin and inhibin.

Ligands

Agonists

Peptides

Antagonists

Peptides

Non-peptides

Clinical implications

Defects in the GnRHR are a cause of hypogonadotropic hypogonadism (HH).[5]

Normal puberty begins between ages 8 and 14 in girls and between 9 and 14 in boys. Puberty, however, for some children can come much sooner or much later or in many cases never occurs and thereby contributes to the estimated 35-70 million infertile couples worldwide. Among children, the abnormally early or late onset of puberty exerts intense emotional and social stress that too often goes untreated.

The timely onset of puberty is regulated by many factors and one factor that is often referred to as the master regulator of puberty and reproduction is GnRH. This peptide hormone is produced in the hypothalamus but gets secreted and acts upon GnRHRs in the anterior pituitary to exert its effects on reproductive maturation.

Understanding how GnRHR functions has been key to developing clinical strategies to treat reproductive-related disorders.[6][7][8]

See also

References

  1. ↑ Millar RP (2005). "GnRHs and GnRH receptors". Anim. Reprod. Sci. 88 (1–2): 5–28. doi:10.1016/j.anireprosci.2005.05.032. PMID 16140177.
  2. ↑ Harrison GS, Wierman ME, Nett TM, Glode LM (2004). "Gonadotropin-releasing hormone and its receptor in normal and malignant cells". Endocr. Relat. Cancer. 11 (4): 725–48. doi:10.1677/erc.1.00777. PMID 15613448.
  3. ↑ Neill JD, Musgrove LC, Duck LW (2004). "Newly recognized GnRH receptors: function and relative role". Trends Endocrinol. Metab. 15 (8): 383–92. doi:10.1016/j.tem.2004.08.005. PMID 15380810.
  4. ↑ Cheng CK, Leung PC (2005). "Molecular biology of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and their receptors in humans". Endocr. Rev. 26 (2): 283–306. doi:10.1210/er.2003-0039. PMID 15561800.
  5. ↑ Layman LC (2007). "Hypogonadotropic hypogonadism". Endocrinol. Metab. Clin. North Am. 36 (2): 283–96. doi:10.1016/j.ecl.2007.03.010. PMID 17543719.
  6. ↑ Re M, Pampillo M, Savard M, Dubuc C, McArdle CA, Millar RP, Conn PM, Gobeil F, Bhattacharya M, Babwah AV (2010). Koch K, ed. "The human gonadotropin releasing hormone type I receptor is a functional intracellular GPCR expressed on the nuclear membrane". PLoS ONE. 5 (7): e11489. doi:10.1371/journal.pone.0011489. PMC 2900216. PMID 20628612.
  7. ↑ Balasubramanian R, Dwyer A, Seminara SB, Pitteloud N, Kaiser UB, Crowley WF (2010). "Human GnRH deficiency: a unique disease model to unravel the ontogeny of GnRH neurons". Neuroendocrinology. 92 (2): 81–99. doi:10.1159/000314193. PMC 3214927. PMID 20606386.
  8. ↑ Viswanathan V, Eugster EA (December 2009). "Etiology and treatment of hypogonadism in adolescents". Endocrinol. Metab. Clin. North Am. 38 (4): 719–38. doi:10.1016/j.ecl.2009.08.004. PMC 4102132. PMID 19944289.

External links


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