Gonadotropin-releasing hormone receptor: Difference between revisions

From Wikipedia, the free encyclopedia
Content deleted Content added
added WP:BUNCH templates; replace external HUGO links with internal wiki links; copyedit
Line 1: Line 1:
{{Fix bunching|beg}}
{{Protein
{{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
Line 14: Line 15:
|UniProt=P30968
|UniProt=P30968
}}
}}
{{Fix bunching|mid}}
{{protein
{{protein
| Name = [[GNRHR2|Gonadotropin-releasing hormone (type 2) receptor 2]]
| Name = [[GNRHR2|Gonadotropin-releasing hormone (type 2) receptor 2]]
Line 20: Line 22:
| width =
| width =
| HGNCid = 16341
| HGNCid = 16341
| Symbol = GNRHR2
| Symbol = [[GNRHR2]]
| AltSymbols =
| AltSymbols =
| EntrezGene = 114814
| EntrezGene = 114814
Line 33: Line 35:
| LocusSupplementaryData =
| LocusSupplementaryData =
}}
}}
{{Fix bunching|end}}

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]].
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]].


Line 40: Line 42:
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 | author = 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>
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 | author = 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>


==Function==
== Function ==
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).
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).


==Gene==
== Genes ==
There are two major forms of the GNRHR, each encoded by a separate receptor ({{gene|GNRHR}}, {{gene|GNRHR2}}).<ref name="pmid15380810">{{cite journal | author = 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 | author = 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 | author = 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 | author = 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 [[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 [[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, [[inhibin]], and [[activin]].
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]].


==Clinical implications==
== Clinical implications ==
{{expert|Medicine|section}}
{{expert|Medicine|section}}
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>
Line 57: Line 59:
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 reproductive [http://en.wiktionary.org/wiki/maturation 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 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]].


Understanding how GnRH-R functions has been key to developing clinical strategies to treat reproductive-related disorders.<ref name="pmid20628612">{{cite journal | author = 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 = }}</ref><ref name="pmid20606386">{{cite journal | author = 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 = }}</ref><ref name="pmid19944289">{{cite journal | author = 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 | year = 2009 | month = December | pmid = 19944289 | doi = 10.1016/j.ecl.2009.08.004 | url = | issn = }}</ref>
Understanding how GnRH-R functions [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0011489] has been key to developing clinical strategies to treat reproductive-related disorders<ref>http://www.ncbi.nlm.nih.gov/pubmed/20606386 Human GnRH Deficiency: A Unique Disease Model to Unravel the Ontogeny of GnRH Neurons.</ref>. Although this receptor has been discovered a long time ago, scientists are still uncovering new information about it and this information will be used to research treatments for puberty and other reproductive-related disorders<ref>http://www.ncbi.nlm.nih.gov/pubmed/19944289 Etiology and treatment of hypogonadism in adolescents</ref>


== References ==
== References ==

Revision as of 04:46, 21 October 2010

Template:Fix bunching

Gonadotropin-releasing hormone receptor
Identifiers
SymbolGNRHR
Alt. symbolsGnRH-R; LRHR;
NCBI gene2798
HGNC4421
OMIM138850
RefSeqNM_000406
UniProtP30968
Other data
LocusChr. 4 q21.2
Search for
StructuresSwiss-model
DomainsInterPro

Template:Fix bunching

Gonadotropin-releasing hormone (type 2) receptor 2
Identifiers
SymbolGNRHR2
NCBI gene114814
HGNC16341
RefSeqNR_002328
UniProtQ96P88
Other data
LocusChr. 1 q12
Search for
StructuresSwiss-model
DomainsInterPro

Template:Fix bunching 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 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 LHRH 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 LHRH and its receptor in extrapituitary tissues as well as a role in progression of some cancers.[2]

Function

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

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.

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 the gonadotropin-releasing hormone (GnRH). GnRH is produced in the hypothalamus but gets secreted and acts upon receptors (GnRH-R) on the anterior pituitary to exert its effects on reproductive maturation.

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

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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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). "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.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  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. PMID 20606386.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Viswanathan V, Eugster EA (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. PMID 19944289. {{cite journal}}: Unknown parameter |month= ignored (help)

External links

Template:Sex hormones