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a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response

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=sense organ / 受信装置

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/15 11:06:08」(JST)

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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

^ 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.
^ 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.
^ 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.
^ 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.
^ Layman LC (2007). "Hypogonadotropic hypogonadism". Endocrinol. Metab. Clin. North Am. 36 (2): 283–96. doi:10.1016/j.ecl.2007.03.010. PMID 17543719.
^ Re M, Pampillo M, Savard M, Dubuc C, McArdle CA, Millar RP, Conn PM, Gobeil F, Bhattacharya M, Babwah AV (2010). Koch, Karl-Wilhelm, 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.
^ 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.
^ 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. PMID 19944289.

External links

"Gonadotrophin-Releasing Hormone Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
GNRHR protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 先天性性腺刺激ホルモン放出ホルモン欠乏症（特発性低ゴナドトロピン性性腺機能低下） congenital gonadotropin releasing hormone deficiency idiopathic hypogonadotropic hypogonadism
2. 子宮平滑筋腫（子宮筋腫）の治療の概要 overview of treatment of uterine leiomyomas fibroids
3. 性腺刺激ホルモン（ゴナドトロピン）放出ホルモンの生理学 physiology of gonadotropin releasing hormone
4. Epidemiology and causes of secondary amenorrhea
5. 男性生殖生理学 male reproductive physiology

English Journal

Pharmacologic profiles of investigational kisspeptin/metastin analogues, TAK-448 and TAK-683, in adult male rats in comparison to the GnRH analogue leuprolide.

Matsui H1, Masaki T2, Akinaga Y2, Kiba A2, Takatsu Y2, Nakata D2, Tanaka A2, Ban J3, Matsumoto S2, Kumano S2, Suzuki A2, Ikeda Y3, Yamaguchi M2, Watanabe T2, Ohtaki T2, Kusaka M3.
European journal of pharmacology.Eur J Pharmacol.2014 Jul 15;735:77-85. doi: 10.1016/j.ejphar.2014.03.058. Epub 2014 Apr 18.
Kisspeptin/metastin, a hypothalamic peptide, plays a pivotal role in controlling gonadotropin-releasing hormone (GnRH) neurons, and we have shown that continuous subcutaneous administration of kisspeptin analogues suppresses plasma testosterone in male rats. This study examined pharmacologic profile
PMID 24747751

Initiation of active immunization against testosterone during early puberty alters negative feedback regulation of the hypothalamic-pituitary-testicular axis in rabbits.

Han XF1, Cheng W1, Chen ZY1, Du XG1, Cao XH1, Zeng XY2.
Domestic animal endocrinology.Domest Anim Endocrinol.2014 Jul;48:126-35. doi: 10.1016/j.domaniend.2014.04.001. Epub 2014 Apr 12.
To investigate the effects of antitestosterone immunization, initiated during early puberty, on hypothalamic-pituitary-testicular feedback in rabbits, 16 early pubertal male rabbits were randomly allocated into 2 groups (n = 8), control or immunized against testosterone-3(O-carboxymethyl)oxime-BSA i
PMID 24906938

Disruption of the hormonal network and the enantioselectivity of bifenthrin in trophoblast: Maternal-fetal health risk of chiral pesticides.

Zhao M, Zhang Y, Zhuang S, Zhang Q, Lu C, Liu W.
Environmental science & technology.Environ Sci Technol.2014 Jun 17. [Epub ahead of print]
Endocrine-disrupting chemicals (EDCs) can interfere with normal hormone signaling to increase health risks to the maternal-fetal system, yet few studies have been conducted on the currently used chiral EDCs. This work tested the hypothesis that pyrethroids could enantioselectively interfere with tro
PMID 24938463

Japanese Journal

Cytoplasmic kinases downstream of GPR30 suppress gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone secretion from bovine anterior pituitary cells

Journal of Reproduction and Development 62(1), 65-69, 2016
NAID 130005126318

Structure–activity relationship study on senktide for development of novel potent neurokinin-3 receptor selective agonists

MedChemComm 6(3), 469-476, 2015-01-05
NAID 120005615647

Effects of Caponization on Expression of Gonadotropin-Releasing Hormone-Ⅰ and Gonadotropin Subunits Genes in Roosters

The Journal of Poultry Science 53(1), 58-62, 2015
NAID 130005120947

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★リンクテーブル★

リンク元	「性腺刺激ホルモン放出ホルモン受容体」「LHRH受容体」「GnRH受容体」「GnRHレセプター」
関連記事	「GnRH」

「性腺刺激ホルモン放出ホルモン受容体」

Gonadotropin-releasing hormone (type 2) receptor 2
Identifiers
Symbol	GNRHR2
Entrez	114814
HUGO	16341
RefSeq	NR_002328
UniProt	Q96P88
Other data
Locus	Chr. 1 q12

Gonadotropin-releasing hormone receptor
Identifiers
Symbol	GNRHR
Alt. symbols	GnRH-R; LRHR;
Entrez	2798
HUGO	4421
OMIM	138850
RefSeq	NM_000406
UniProt	P30968
Other data
Locus	Chr. 4 q21.2