グルココルチコイド受容体、グルココルチコイドレセプター、糖質コルチコイド受容体

関: GR

WordNet

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
a steroid hormone that is produced by the adrenal cortex of animals; affects functioning of gonads and has anti-inflammatory activity

PrepTutorEJDIC

=sense organ / 受信装置

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/10/07 12:32:17」(JST)

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[Wiki en表示]

The glucocorticoid receptor (GR, or GCR) also known as NR3C1 (nuclear receptor subfamily 3, group C, member 1) is the receptor to which cortisol and other glucocorticoids bind.

The GR is expressed in almost every cell in the body and regulates genes controlling the development, metabolism, and immune response. Because the receptor gene is expressed in several forms, it has many different (pleiotropic) effects in different parts of the body.

When the GR binds to glucocorticoids, its primary mechanism of action is the regulation of gene transcription.^[3]^[4] The unbound receptor resides in the cytosol of the cell. After the receptor is bound to glucocorticoid, the receptor-glucorticoid complex can take either of two paths. The activated GR complex up-regulates the expression of anti-inflammatory proteins in the nucleus or represses the expression of pro-inflammatory proteins in the cytosol (by preventing the translocation of other transcription factors from the cytosol into the nucleus).

In humans, the GR protein is encoded by NR3C1 gene which is located on chromosome 5 (5q31).^[5]^[6]

Structure

Like the other steroid receptors,^[7] the glucocorticoid receptor is modular in structure^[8] and contains the following domains (labeled A - F):

A/B - N-terminal regulatory domain
C - DNA-binding domain (DBD)
D - hinge region
E - ligand-binding domain (LBD)
F - C-terminal domain

Ligand binding and response

In the absence of hormone, the glucocorticoid receptor (GR) resides in the cytosol complexed with a variety of proteins including heat shock protein 90 (hsp90), the heat shock protein 70 (hsp70) and the protein FKBP52 (FK506-binding protein 52).^[9] The endogenous glucocorticoid hormone cortisol diffuses through the cell membrane into the cytoplasm and binds to the glucocorticoid receptor (GR) resulting in release of the heat shock proteins. The resulting activated form GR has two principal mechanisms of action, transactivation and transrepression,^[10]^[11] described below.

Transactivation

A direct mechanism of action involves homodimerization of the receptor, translocation via active transport into the nucleus, and binding to specific DNA responsive elements activating gene transcription. This mechanism of action is referred to as transactivation. The biologic response depends on the cell type.

Transrepression

In the absence of activated GR, other transcription factors such as NF-κB or AP-1 themselves are able to transactivate target genes.^[12] However activated GR can complex with these other transcription factors and prevent them from binding their target genes and hence repress the expression of genes that are normally upregulated by NF-κB or AP-1. This indirect mechanism of action is referred to as transrepression.

Clinical significance

The GR is abnormal in familial glucocorticoid resistance.^[13]

In central nervous system structures, the glucocorticoid receptor is gaining interest as a novel representative of neuroendocrine integration, functioning as a major component of endocrine influence - specifically the stress response - upon the brain. The receptor is now implicated in both short and long-term adaptations seen in response to stressors and may be critical to the understanding of psychological disorders, including some or all subtypes of depression and post-traumatic stress disorder (PTSD).^[14] Indeed, long-standing observations such as the mood dysregulations typical of Cushing's disease demonstrate the role of corticosteroids in regulating psychologic state; recent advances have demonstrated interactions with norepinephrine and serotonin at the neural level.^[15]^[16]

Agonists and antagonists

Dexamethasone and other corticosteroids are agonists, and mifepristone and ketoconazole are antagonists of the GR.

Interactions

Glucocorticoid receptor has been shown to interact with:

BAG1,^[17]^[18]
CEBPB,^[19]
CREBBP,^[20]
DAP3,^[21]
DAXX,^[22]
HSP90AA1,^[21]^[23]^[24]^[25]^[26]^[27]^[28]
HNRPU,^[29]
MED1,^[30]^[31]
MED14,^[31]
Mineralocorticoid receptor,^[32]
NRIP1,^[30]^[33]^[34]
NCOR1,^[35]^[36]
NCOA1,^[30]^[37]
NCOA2,^[30]^[38]
NCOA3,^[30]^[39]
POU2F1,^[40]^[40]^[41]
RANBP9,^[42]
RELA,^[42]^[43]^[44]
SMAD3,^[45]^[46]
SMARCD1,^[39]
SMARCA4^[39]^[47]
STAT3,^[48]^[49]
STAT5B,^[50]
Thioredoxin,^[51]
TRIM28,^[52] and
YWHAH.^[53]

References

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^ "Mouse PubMed Reference:".
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^ Stancato LF, Silverstein AM, Gitler C, Groner B, Pratt WB (April 1996). "Use of the thiol-specific derivatizing agent N-iodoacetyl-3-[125I]iodotyrosine to demonstrate conformational differences between the unbound and hsp90-bound glucocorticoid receptor hormone binding domain". J. Biol. Chem. 271 (15): 8831–6. doi:10.1074/jbc.271.15.8831. PMID 8621522.
^ Eggert M, Michel J, Schneider S, Bornfleth H, Baniahmad A, Fackelmayer FO, Schmidt S, Renkawitz R (November 1997). "The glucocorticoid receptor is associated with the RNA-binding nuclear matrix protein hnRNP U". J. Biol. Chem. 272 (45): 28471–8. doi:10.1074/jbc.272.45.28471. PMID 9353307.
^ ^a ^b ^c ^d ^e Zilliacus J, Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson JA (April 2001). "Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140". Mol. Endocrinol. 15 (4): 501–11. doi:10.1210/mend.15.4.0624. PMID 11266503.
^ ^a ^b Hittelman AB, Burakov D, Iñiguez-Lluhí JA, Freedman LP, Garabedian MJ (October 1999). "Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins". EMBO J. 18 (19): 5380–8. doi:10.1093/emboj/18.19.5380. PMC 1171607. PMID 10508170.
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^ Stevens A, Garside H, Berry A, Waters C, White A, Ray D (May 2003). "Dissociation of steroid receptor coactivator 1 and nuclear receptor corepressor recruitment to the human glucocorticoid receptor by modification of the ligand-receptor interface: the role of tyrosine 735". Mol. Endocrinol. 17 (5): 845–59. doi:10.1210/me.2002-0320. PMID 12569182.
^ Schulz M, Eggert M, Baniahmad A, Dostert A, Heinzel T, Renkawitz R (July 2002). "RU486-induced glucocorticoid receptor agonism is controlled by the receptor N terminus and by corepressor binding". J. Biol. Chem. 277 (29): 26238–43. doi:10.1074/jbc.M203268200. PMID 12011091.
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^ ^a ^b Rao, Mira A; Cheng Helen; Quayle Alandra N; Nishitani Hideo; Nelson Colleen C; Rennie Paul S (Dec 2002). "RanBPM, a nuclear protein that interacts with and regulates transcriptional activity of androgen receptor and glucocorticoid receptor". J. Biol. Chem. United States. 277 (50): 48020–7. doi:10.1074/jbc.M209741200. ISSN 0021-9258. PMID 12361945.
^ Nissen RM, Yamamoto KR (September 2000). "The glucocorticoid receptor inhibits NFkappaB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain". Genes Dev. 14 (18): 2314–29. doi:10.1101/gad.827900. PMC 316928. PMID 10995388.
^ Caldenhoven E, Liden J, Wissink S, Van de Stolpe A, Raaijmakers J, Koenderman L, Okret S, Gustafsson JA, Van der Saag PT (April 1995). "Negative cross-talk between RelA and the glucocorticoid receptor: a possible mechanism for the antiinflammatory action of glucocorticoids". Mol. Endocrinol. 9 (4): 401–12. doi:10.1210/me.9.4.401. PMID 7659084.
^ Li G, Wang S, Gelehrter TD (October 2003). "Identification of glucocorticoid receptor domains involved in transrepression of transforming growth factor-beta action". J. Biol. Chem. 278 (43): 41779–88. doi:10.1074/jbc.M305350200. PMID 12902338.
^ Song CZ, Tian X, Gelehrter TD (October 1999). "Glucocorticoid receptor inhibits transforming growth factor-beta signaling by directly targeting the transcriptional activation function of Smad3". Proc. Natl. Acad. Sci. U.S.A. 96 (21): 11776–81. doi:10.1073/pnas.96.21.11776. PMC 18362. PMID 10518526.
^ Wallberg AE, Neely KE, Hassan AH, Gustafsson JA, Workman JL, Wright AP (March 2000). "Recruitment of the SWI-SNF chromatin remodeling complex as a mechanism of gene activation by the glucocorticoid receptor tau1 activation domain". Mol. Cell. Biol. 20 (6): 2004–13. doi:10.1128/MCB.20.6.2004-2013.2000. PMC 110817. PMID 10688647.
^ Lerner L, Henriksen MA, Zhang X, Darnell JE (October 2003). "STAT3-dependent enhanceosome assembly and disassembly: synergy with GR for full transcriptional increase of the alpha 2-macroglobulin gene". Genes Dev. 17 (20): 2564–77. doi:10.1101/gad.1135003. PMC 218150. PMID 14522952.
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External links

Human Protein Reference Database
Glucocorticoid receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
FactorBook GR

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2. ステロイドの薬理学的使用 pharmacologic use of glucocorticoids
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4. 敗血症性ショックのステロイド療法 corticosteroid therapy in septic shock
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English Journal

T regulatory markers expression in unexplained recurrent spontaneous abortion.

Saifi B1,2, Aflatoonian R3, Tajik N4, Erfanian Ahmadpour M2, Vakili R5, Amjadi F1, Valizade N6, Ahmadi S5, Rezaee SA6, Mehdizadeh M7.
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.J Matern Fetal Neonatal Med.2016 Apr;29(7):1175-80. doi: 10.3109/14767058.2015.1039507. Epub 2015 Jun 2.
OBJECTIVE: To evaluate expression of glucocorticoid-induced tumor necrosis factor receptor (GITR), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and IL-10 in peripheral blood mononuclear cells (PBMCs) of 20 women with unexplained recurrent spontaneous abortion (URSA) compared to 20 normal non
PMID 26037627

Expression of hepatic miRNAs targeting porcine glucocorticoid receptor (GR) 3'UTR in the neonatal piglets under a maternal gestational betaine supplementation.

Cai D1, Liu H2, Yuan M1, Pan S3, Jia Y1, Zhao R1.
Data in brief.Data Brief.2015 Nov 26;6:4-7. doi: 10.1016/j.dib.2015.11.037. eCollection 2016.
Glucocorticoid receptor (GR) has been previously demonstrated an important transcriptional factor of hepatic metabolic genes in the neonates under a maternal gestational betaine supplementation ("Gestational dietary betaine supplementation suppresses hepatic expression of lipogenic genes in neonatal
PMID 26759820

Hippocampal microglial activation and glucocorticoid receptor down-regulation precipitate visceral hypersensitivity induced by colorectal distension in rats.

Zhang G1, Zhao BX2, Hua R3, Kang J2, Shao BM2, Carbonaro TM4, Zhang YM5.
Neuropharmacology.Neuropharmacology.2016 Mar;102:295-303. doi: 10.1016/j.neuropharm.2015.11.028. Epub 2015 Dec 2.
Visceral hypersensitivity is a common characteristic in patients suffering from irritable bowel syndrome (IBS) and other disorders with visceral pain. Although the pathogenesis of visceral hypersensitivity remains speculative due to the absence of pathological changes, the long-lasting sensitization
PMID 26656865

Japanese Journal

去勢抵抗性前立腺がんの緩和医療における合成グルココルチコイドの有用性と有害性

茅根義和,井上重治
日本緩和医療薬学雑誌 5(2), 19-29, 2012-06
NAID 40019405965

Glucocorticoids Decrease Astrocyte Numbers by Reducing Glucocorticoid Receptor Expression In Vitro and In Vivo

Unemura Kazuhiro,Kume Toshiaki,Kondo Minami [他]
Journal of pharmacological sciences 119(1), 30-39, 2012-05
NAID 40019255662

Related Pictures

★リンクテーブル★

リンク元	「糖質コルチコイド受容体」「グルココルチコイドレセプター」「グルココルチコイド受容体」「GR」
関連記事	「glucocorticoid」

「糖質コルチコイド受容体」

NR3C1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1M2Z, 1NHZ, 1P93, 3BQD, 3CLD, 3E7C, 3H52, 3K22, 3K23, 4CSJ, 4HN5, 4HN6, 4LSJ, 4MDD, 4P6W, 4P6X, 5CBY, 5CBX, 4UDC, 4UDD, 5CBZ, 5CC1, 5EMQ, 5EMC, 5EMP
Identifiers
Aliases	NR3C1, GCCR, GCR, GCRST, GR, GRL, nuclear receptor subfamily 3 group C member 1, Glucocorticoid Receptor
External IDs	MGI: 95824 HomoloGene: 30960 GeneCards: 2908
Gene ontology
Molecular function	• steroid hormone binding; • DNA binding; • sequence-specific DNA binding; • transcription factor activity, sequence-specific DNA binding; • zinc ion binding; • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; • glucocorticoid receptor activity; • glucocorticoid-activated RNA polymerase II transcription factor binding transcription factor activity; • metal ion binding; • RNA polymerase II core promoter proximal region sequence-specific DNA binding; • steroid hormone receptor activity; • steroid binding; • protein binding; • lipid binding; • RNA binding; • protein complex binding;
Cellular component	• cytoplasm; • nucleoplasm; • mitochondrial matrix; • mitochondrion; • nucleus; • cytoskeleton; • protein complex; • spindle; • microtubule organizing center;
Biological process	• cellular response to steroid hormone stimulus; • regulation of transcription, DNA-templated; • glucocorticoid mediated signaling pathway; • transcription from RNA polymerase II promoter; • transcription, DNA-templated; • transcription initiation from RNA polymerase II promoter; • glucocorticoid receptor signaling pathway; • signal transduction; • positive regulation of transcription from RNA polymerase II promoter; • steroid hormone mediated signaling pathway; • mitotic nuclear division; • cell cycle; • cell division; • apoptotic process; • chromosome segregation; • chromatin modification;
	Sources:Amigo / QuickGO
RNA expression pattern
	; ; ; ;
	More reference expression data
Orthologs
	2908
	14815
	ENSG00000113580
	ENSMUSG00000024431
	P04150; Q3MSN4
	P06537
NM_000176; NM_001018074; NM_001018075; NM_001018076; NM_001018077;
	NM_001020825; NM_001024094; NM_001204258; NM_001204259; NM_001204260; NM_001204261; NM_001204262; NM_001204263; NM_001204264; NM_001204265
	NM_008173
NP_000167.1; NP_001018084.1; NP_001018085.1; NP_001018086.1; NP_001018087.1;
	NP_001018661.1; NP_001019265.1; NP_001191187.1; NP_001191188.1; NP_001191189.1; NP_001191190.1; NP_001191191.1; NP_001191192.1; NP_001191193.1; NP_000167.1; NP_001018084.1; NP_001018085.1; NP_001018086.1; NP_001018087.1; NP_001018661.1; NP_001019265.1; NP_001191187.1; NP_001191188.1; NP_001191189.1; NP_001191190.1; NP_001191191.1; NP_001191192.1; NP_001191193.1
	n/a
	Wikidata
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　　[★]

英: glucocorticoid receptor GR
関: グルココルチコイド受容体、グルココルチコイドレセプター

「グルココルチコイドレセプター」

　　[★]

英: glucocorticoid receptor
関: グルココルチコイド受容体、糖質コルチコイド受容体

「グルココルチコイド受容体」

　　[★]

英: glucocorticoid receptor, GR
関: グルココルチコイド

「GR」

　　[★]

グルココルチコイド受容体

関: glucocorticoid receptor

「glucocorticoid」

　　[★] 糖質コルチコイド　

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glucocorticoid receptor