- 同
- corticosteroid-binding globulin
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/08/27 17:14:37」(JST)
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| SERPINA6 |
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| Available structures |
| PDB |
Ortholog search: PDBe RCSB |
| List of PDB id codes |
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2VDX, 2VDY, 4BB2, 4C41, 4C49
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| Identifiers |
| Aliases |
SERPINA6, CBG, serpin family A member 6 |
| External IDs |
OMIM: 122500 MGI: 88278 HomoloGene: 20417 GeneCards: 866 |
| Gene ontology |
| Molecular function |
• steroid binding
• serine-type endopeptidase inhibitor activity
• lipid binding
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| Cellular component |
• extracellular space
• extracellular region
• extracellular exosome
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| Biological process |
• transport
• glucocorticoid metabolic process
• negative regulation of endopeptidase activity
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| Sources:Amigo / QuickGO |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
| Entrez |
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| Ensembl |
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| UniProt |
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| RefSeq (mRNA) |
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| RefSeq (protein) |
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| Location (UCSC) |
Chr 14: 94.3 – 94.32 Mb |
Chr 12: 103.65 – 103.66 Mb |
| PubMed search |
[1] |
[2] |
| Wikidata |
| View/Edit Human |
View/Edit Mouse |
Transcortin, also known as corticosteroid-binding globulin (CBG) or serpin A6 is a protein that in humans is encoded by the SERPINA6 gene. It is an alpha-globulin.[3][4][5]
Contents
- 1 Function
- 2 Binding
- 3 Synthesis
- 4 Clinical significance
- 5 See also
- 6 References
- 7 Further reading
- 8 External links
Function
This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucocorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors (serpins) which have evolved by duplication events.[5]
Binding
Transcortin binds several steroid hormones at high rates:
- Cortisol - Approximately 75% of the cortisol in circulation is bound to transcortin. (The rest is bound to serum albumin.) Cortisol is thought to be biologically active only when it is not bound to transcortin.[citation needed]
- Cortisone[6]
- Deoxycorticosterone (DOC)[6]
- Corticosterone - About 78% of serum corticosterone is bound to transcortin.
- Aldosterone - Approximately 17% of serum aldosterone is bound to transcortin, while another 47% is bound to serum albumin. The remaining 36% is free.[7]
- Progesterone - Approximately 18% of serum progesterone is bound to transcortin, while another 80% of it is bound to serum albumin. The remaining 2% is free.[8]
- 17-Hydroxyprogesterone[6]
In addition, approximately 4% of serum testosterone is bound to transcortin.[9] A similarly small fraction of serum estradiol is bound to transcortin as well.[citation needed]
Synthesis
Transcortin is produced by the liver and is increased by estrogens.[10]
Clinical significance
Mutations in this gene are rare. Only four mutations have been described, often in association with fatigue and chronic pain.[11] This mechanism for these symptoms is not known. This condition must be distinguished from secondary hypocortisolism. Exogenous hydrocortisone does not appear to improve the fatigue.
Hepatic synthesis of corticosteroid-binding globulin more than doubles in pregnancy; that is, unbound plasma cortisol in term pregnancy is approximately 2.5 times that of nonpregnant women.[12]
See also
- Serpin
- Circaseptan, 7-day biological cycle
References
- ^ "Human PubMed Reference:".
- ^ "Mouse PubMed Reference:".
- ^ Hammond GL, Smith CL, Goping IS, Underhill DA, Harley MJ, Reventos J, Musto NA, Gunsalus GL, Bardin CW (Aug 1987). "Primary structure of human corticosteroid binding globulin, deduced from hepatic and pulmonary cDNAs, exhibits homology with serine protease inhibitors". Proc Natl Acad Sci U S A. 84 (15): 5153–7. doi:10.1073/pnas.84.15.5153. PMC 298812. PMID 3299377.
- ^ Byth BC, Billingsley GD, Cox DW (Jul 1994). "Physical and genetic mapping of the serpin gene cluster at 14q32.1: allelic association and a unique haplotype associated with alpha 1-antitrypsin deficiency". Am J Hum Genet. 55 (1): 126–33. PMC 1918218. PMID 7912884.
- ^ a b "Entrez Gene: SERPINA6 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6".
- ^ a b c E. Edward Bittar; Neville Bittar (1997). Molecular and Cellular Endocrinology. Elsevier. p. 238. ISBN 978-1-55938-815-3. Retrieved 23 August 2012.
- ^ Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. 24 April 2001. p. 712. ISBN 978-0-7817-1750-2. Retrieved 23 August 2012.
- ^ Negi (2009). Introduction To Endocrinology. PHI Learning Pvt. Ltd. p. 268. ISBN 978-81-203-3850-0. Retrieved 23 August 2012.
- ^ Dunn JF, Nisula BC, Rodbard D (July 1981). "Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma". The Journal of Clinical Endocrinology and Metabolism. 53 (1): 58–68. doi:10.1210/jcem-53-1-58. PMID 7195404.
- ^ Musa BU, Seal US, Doe RP (September 1965). "Elevation of certain plasma proteins in man following estrogen administration: a dose-response relationship". J. Clin. Endocrinol. Metab. 25 (9): 1163–6. doi:10.1210/jcem-25-9-1163. PMID 4284083.
- ^ Torpy DJ, Lundgren BA, Ho JT, Lewis JG, Scott HS, Mericq V (January 2012). "CBG Santiago: a novel CBG mutation". J. Clin. Endocrinol. Metab. 97 (1): E151–5. doi:10.1210/jc.2011-2022. PMID 22013108.
- ^ Rosen MI, Shnider SM, Levinson G, Hughes (2002). Shnider and Levinson's anesthesia for obstetrics. Hagerstwon, MD: Lippincott Williams & Wilkins. p. 13. ISBN 0-683-30665-0.
Further reading
- Rosner W, Beers PC, Awan T, Khan MS (1976). "Identification of corticosteroid-binding globulin in human milk: measurement with a filter disk assay.". J. Clin. Endocrinol. Metab. 42 (6): 1064–73. doi:10.1210/jcem-42-6-1064. PMID 932172.
- Smith CL, Power SG, Hammond GL (1992). "A Leu----His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol.". J. Steroid Biochem. Mol. Biol. 42 (7): 671–6. doi:10.1016/0960-0760(92)90107-T. PMID 1504007.
- Brotherton J (1990). "Cortisol and transcortin in human seminal plasma and amniotic fluid as estimated by modern specific assays.". Andrologia. 22 (3): 197–204. doi:10.1111/j.1439-0272.1990.tb01966.x. PMID 2240617.
- Seralini GE, Bérubé D, Gagné R, Hammond GL (1991). "The human corticosteroid binding globulin gene is located on chromosome 14q31-q32.1 near two other serine protease inhibitor genes.". Hum. Genet. 86 (1): 73–5. doi:10.1007/bf00205177. PMID 2253941.
- Underhill DA, Hammond GL (1990). "Organization of the human corticosteroid binding globulin gene and analysis of its 5'-flanking region.". Mol. Endocrinol. 3 (9): 1448–54. doi:10.1210/mend-3-9-1448. PMID 2608068.
- Loric S, Egloff M, Domingo M, et al. (1990). "Immunochemical characterization of corticosteroid-binding globulin in human bronchoalveolar fluid.". Clin. Chim. Acta. 186 (1): 19–23. doi:10.1016/0009-8981(89)90198-8. PMID 2612005.
- Heubner A, Belovsky O, Müller W, et al. (1987). "Application of liquid-liquid partition chromatography in the simultaneous purification of sex-hormone-binding globulin and corticosteroid-binding globulin.". J. Chromatogr. 397: 419–34. doi:10.1016/S0021-9673(01)85027-5. PMID 2821037.
- Kato EA, Hsu BR, Kuhn RW (1988). "Comparative structural analyses of corticosteroid binding globulin.". J. Steroid Biochem. 29 (2): 213–20. doi:10.1016/0022-4731(88)90268-3. PMID 3347061.
- Bardin CW, Gunsalus GL, Musto NA, et al. (1988). "Corticosteroid binding globulin, testosterone-estradiol binding globulin, and androgen binding protein belong to protein families distinct from steroid receptors.". J. Steroid Biochem. 30 (1-6): 131–9. doi:10.1016/0022-4731(88)90085-4. PMID 3386241.
- Hammond GL, Langley MS (1986). "Identification and measurement of sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) in human saliva.". Acta Endocrinol. 112 (4): 603–8. doi:10.1530/acta.0.1120603. PMID 3751467.
- Agrimonti F, Frairia R, Fornaro D, et al. (1983). "Circadian and circaseptan rhythmicities in corticosteroid-binding globulin (CBG) binding activity of human milk.". Chronobiologia. 9 (3): 281–90. PMID 7172869.
- Misao R, Hori M, Ichigo S, et al. (1995). "Levels of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) messenger ribonucleic acid (mRNAs) in ovarian endometriosis.". Reprod. Nutr. Dev. 35 (2): 155–65. doi:10.1051/rnd:19950204. PMID 7734053.
- Misao R, Hori M, Ichigo S, et al. (1995). "Corticosteroid-binding globulin mRNA levels in human uterine endometrium.". Steroids. 59 (10): 603–7. doi:10.1016/0039-128X(94)90055-8. PMID 7878688.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene. 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Avvakumov GV, Hammond GL (1994). "Glycosylation of human corticosteroid-binding globulin. Differential processing and significance of carbohydrate chains at individual sites.". Biochemistry. 33 (19): 5759–65. doi:10.1021/bi00185a012. PMID 8180202.
- Van Baelen H, Power SG, Hammond GL (1993). "Decreased cortisol-binding affinity of transcortin Leuven is associated with an amino acid substitution at residue-93.". Steroids. 58 (6): 275–7. doi:10.1016/0039-128X(93)90072-U. PMID 8212073.
- Misao R, Nakanishi Y, Fujimoto J, et al. (1996). "Expression of corticosteroid-binding globulin mRNA in human uterine endometrial cancers.". Steroids. 60 (10): 720–4. doi:10.1016/0039-128X(95)00106-Z. PMID 8539782.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene. 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
External links
- Transcortin at the US National Library of Medicine Medical Subject Headings (MeSH)
- The MEROPS online database for peptidases and their inhibitors: I04.954
- SERPINA6 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
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Proteins: carrier proteins
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| Fatty acid |
- FABP1
- FABP2
- FABP3
- FABP4
- FABP5
- FABP6
- FABP7
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| Hormone |
- peptide hormone: Follistatin
- Growth hormone binding protein
- Insulin-like growth factor binding protein
- IGFBP1
- IGFBP2
- IGFBP3
- IGFBP4
- IGFBP5
- IGFBP6
- IGFBP7
- Neurophysins
- steroid hormone: Sex hormone binding globulin/Androgen binding protein
- Transcortin
- Thyroxine-binding globulin
- Transthyretin
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| Metal/element |
- calcium
- Calcium-binding protein
- Calmodulin-binding proteins
- copper
- iron
- Iron-binding proteins
- Transferrin receptor
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| Vitamin |
- Retinol binding protein
- Transcobalamin
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| Pigment |
- Plant Light-Harvesting Complex
- Orange Carotenoid Protein
- Phycobiliprotein
- Photosynthetic Reaction Centers
- Phytochrome
- Rhodopsin
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| Other |
- Acyl carrier protein
- Adaptor protein
- Cholesterylester transfer protein
- F-box protein
- GTP-binding protein
- Latent TGF-beta binding protein
- Major urinary proteins
- Membrane transport protein
- Odorant binding protein
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Proteins: Globular proteins
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| Serum globulins |
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Alpha globulins
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serpins:
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- alpha-1 (Alpha 1-antichymotrypsin, Alpha 1-antitrypsin)
- alpha-2 (Alpha 2-antiplasmin)
- Antithrombin (Heparin cofactor II)
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carrier proteins:
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- alpha-1 (Transcortin)
- alpha-2 (Ceruloplasmin)
- Retinol binding protein
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other:
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- alpha-1 (Orosomucoid)
- alpha-2 (alpha-2-Macroglobulin, Haptoglobin)
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Beta globulins
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carrier proteins:
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- Sex hormone-binding globulin
- Transferrin
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other:
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- Angiostatin
- Hemopexin
- Beta-2 microglobulin
- Factor H
- Plasminogen
- Properdin
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Gamma globulin
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Other
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- Fibronectin (fFN: Fetal fibronectin)
- Macroglobulin/Microglobulin
- Transcobalamin
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| Other globulins |
- Beta-lactoglobulin
- Thyroglobulin
- Alpha-lactalbumin
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| Albumins |
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Egg white
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- Conalbumin
- Ovalbumin
- Avidin
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Serum albumin
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- Human serum albumin
- Bovine serum albumin
- Prealbumin
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Other
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- C-reactive protein
- Lactalbumin (Alpha-lactalbumin)
- Parvalbumin
- Ricin
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- see also disorders of globin and globulin proteins
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Serpins
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| inhibitory |
- Alpha 1-antichymotrypsin
- Alpha 1-antitrypsin
- Alpha 2-antiplasmin
- Antithrombin
- C1-inhibitor
- Heparin cofactor II
- Protein C inhibitor
- Plasminogen activator inhibitor-1
- Plasminogen activator inhibitor-2
- Protein Z-related protease inhibitor
- SERPINA1
- SERPINA2
- SERPINA3
- SERPINA4
- SERPINA5
- SERPINA6
- SERPINA7
- SERPINA8
- SERPINA9
- SERPINA14
- SERPINB1
- SERPINB2
- SERPINB3
- SERPINB4
- SERPINB5
- SERPINB6
- SERPINB7
- SERPINB8
- SERPINB9
- SERPINB13
- SERPINC1
- SERPIND1
- SERPINE1
- SERPINE2
- SERPINE2
- SERPINF1
- SERPING1
- SERPINH1
- SERPINI1
- SERPINI2
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| Cross class inhibitory |
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| noninhibitory |
- Heat shock protein 47
- Maspin
- Ovalbumin
- SERPINF1
- Thyroxine-binding globulin
- Transcortin
- SERPINF1
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see also disorders of globin and globulin proteins
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Protein, glycoconjugate: glycoproteins and glycopeptides
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| Mucoproteins |
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Mucin
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- CD43
- CD164
- MUC1
- MUC2
- MUC3A
- MUC3B
- MUC4
- MUC5AC
- MUC5B
- MUC6
- MUC7
- MUC8
- MUC12
- MUC13
- MUC15
- MUC16
- MUC17
- MUC19
- MUC20
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Other
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- Haptoglobin
- Intrinsic factor
- Orosomucoid
- Peptidoglycan
- Phytohaemagglutinin
- Ovomucin
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| Proteoglycans |
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CS/DS
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- Decorin
- Biglycan
- Versican
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HS/CS
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CS
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- Chondroitin sulfate proteoglycans: Aggrecan
- Neurocan
- Brevican
- CD44
- CSPG4
- CSPG5
- Platelet factor 4
- Structural maintenance of chromosomes 3
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KS
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- Fibromodulin
- Lumican
- Keratocan
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HS
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| Other |
- Activin and inhibin
- ADAM
- Alpha 1-antichymotrypsin
- Apolipoprotein H
- CD70
- Asialoglycoprotein
- Avidin
- B-cell activating factor
- 4-1BB ligand
- Cholesterylester transfer protein
- Clusterin
- Colony-stimulating factor
- Hemopexin
- Lactoferrin
- Membrane glycoproteins
- Myelin protein zero
- Osteonectin
- Protein C
- Protein S
- Serum amyloid P component
- Sialoglycoprotein
- CD43
- Glycophorin
- Glycophorin C
- Thrombopoietin
- Thyroglobulin
- Thyroxine-binding proteins
- Transcortin
- Tumor necrosis factor alpha
- Uteroglobin
- Vitronectin
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Glucocorticoid receptor modulators
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| GR |
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Agonists
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Mixed (SEGRAs)
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- Dagrocorat
- Fosdagrocorat
- Mapracorat
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Antagonists
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- 3α-Hydroxytibolone
- 3β-Hydroxytibolone
- Aglepristone
- Asoprisnil
- C108297
- C113176
- CORT-108297
- Cyproterone acetate
- Guggulsterone
- Ketoconazole
- Lilopristone
- LLY-2707
- Miconazole
- Mifepristone
- Onapristone
- ORG-34116
- ORG-34517 (SCH-900636)
- ORG-34850
- Pregnenolone 16α-carbonitrile
- Telapristone
- Tibolone
- Toripristone
- Ulipristal acetate
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| Others |
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Indirect
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- ACTH (corticotropin)
- CRH
- DHEA
- DHEA sulfate
- Plasma proteins (albumin, transcortin)
- Steroidogenesis modulators
- Vasopressin
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See also: Androgenics • Estrogenics • Mineralocorticoidics • Progestogenics • Steroid hormone metabolism modulators
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Mineralocorticoid receptor modulators
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| MR |
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Agonists
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- 11-Deoxycorticosterone (desoxycortone)
- 11-Deoxycortisol (cortodoxone)
- 16α,18-Dihydroxy-11-deoxycorticosterone
- 17-Hydroxyaldosterone
- 18-Hydroxy-11-deoxycorticosterone
- 19-Norprogesterone
- Aldosterone
- Corticosterone
- Desoxycortone acetate
- Desoxycortone enanthate
- Desoxycortone glucoside
- Desoxycortone pivalate
- Hydrocortisone (cortisol)
- Fludrocortisone
- Fludrocortisone acetate
- Mometasone furoate
- Prednisolone
- Prednisone
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Antagonists
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- Steroidal: 3α-Hydroxytibolone
- 3β-Hydroxytibolone
- 6β-Hydroxy-7α-thiomethylspironolactone
- 7α-Thiomethylspironolactone
- 17-Hydroxyprogesterone
- 18-Deoxyaldosterone
- Canrenoate potassium (potassium canrenoate)
- Canrenoic acid
- Canrenone
- Dicirenone
- Drospirenone
- Dydrogesterone
- Eplerenone
- Gestodene
- Guggulsterone
- Mespirenone
- Mexrenoate potassium
- Mexrenoic acid
- Mexrenone
- Oxprenoic acid
- Oxprenoate potassium (RU-28318)
- Pregnenolone
- Progesterone
- Prorenoate potassium
- Prorenoic acid (prorenoate)
- Prorenone
- Quingestrone
- RO-14-9012
- RU-26752
- SC-5233
- SC-8109
- SC-11927
- SC-19886
- SC-24813
- SC-25152
- SC-26519
- SC-27169
- Spirorenone
- Spironolactone
- Spiroxasone
- Tibolone
- Trimegestone
- ZK-91587
- ZK-97894
- Non-steroidal: Amlodipine
- Apararenone
- Benidipine
- BR-4628
- Esaxerenone
- Felodipine
- Finerenone
- Nifedipine
- Nimodipine
- Nitrendipine
- PF-03882845
- SM-368229
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| Others |
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Indirect
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- ACTH (corticotropin)
- CRH
- Plasma proteins (albumin, transcortin)
- Steroidogenesis modulators
- Vasopressin
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See also: Androgenics • Estrogenics • Glucocorticoidics • Progestogenics • Steroid hormone metabolism modulators
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Progesterone receptor modulators
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| PR |
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Agonists
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Mixed (SPRMs)
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- Apigenin
- Asoprisnil
- Asoprisnil ecamate
- Guggulsterone
- Kaempferol
- J1042
- LG-120838
- Naringenin
- PRA-910
- Syringic acid
- Telapristone
- Antagonistic: Mifepristone
- Org-31710
- Org-33628
- Ulipristal acetate
- ZK-137316
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Antagonists
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- 3α-Hydroxytibolone
- 3β-Hydroxytibolone
- Aglepristone
- Lilopristone
- Lonaprisan
- Onapristone
- Toripristone
- Valproic acid
- Vilaprisan
- Zanoterone
- ZM-150271
- ZM-172406
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mPRs
(PAQRs) |
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Agonists
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- 5α-Dihydroprogesterone
- 5β-Dihydroprogesterone
- 11-Deoxycorticosterone
- 17α-Hydroxyprogesterone
- 17α,21-Dihydroxyprogesterone
- 21-Hydroxyprogesterone
- Allopregnanolone
- Mifepristone
- Pregnenolone
- Progesterone
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Antagonists
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| Others |
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Indirect
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- Antigonadotropins (e.g., androgens, estrogens, progestogens, prolactin)
- GnRH agonists (e,g, GnRH, leuprorelin)
- GnRH antagonists (e.g., cetrorelix)
- Gonadotropins (e.g., FSH, hCG, LH)
- Plasma proteins (albumin, transcortin)
- Progonadotropins
- Steroidogenesis modulators
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See also: Androgenics • Estrogenics • Glucocorticoidics • Mineralocorticoidics • Steroid hormone metabolism modulators
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UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- Corticosteroid-binding globulin cleavage may be pathogen-dependent in bloodstream infection.
- Nenke MA1, Lewis JG2, Rankin W3, Shaw D4, Torpy DJ5.
- Clinica chimica acta; international journal of clinical chemistry.Clin Chim Acta.2017 Jan;464:176-181. doi: 10.1016/j.cca.2016.11.033. Epub 2016 Nov 22.
- OBJECTIVE: The process of enzymatic cleavage of high- to low-affinity corticosteroid-binding globulin (haCBG to laCBG) by neutrophil elastase leads to local tissue release of cortisol. Recently Pseudomonas aeruginosa was shown to instigate CBG cleavage with release of free cortisol in vitro. Hence,
- PMID 27887960
- Emerging Role of Corticosteroid-Binding Globulin in Glucocorticoid-Driven Metabolic Disorders.
- Moisan MP1, Castanon N1.
- Frontiers in endocrinology.Front Endocrinol (Lausanne).2016 Dec 19;7:160. doi: 10.3389/fendo.2016.00160. eCollection 2016.
- Glucocorticoid hormones (GCs) are critical for survival since they ensure the energy supply necessary to the body in an ever challenging environment. GCs are known to act on appetite, glucose metabolism, fatty acid metabolism, and storage. However, to be beneficial to the body, GC levels should be m
- PMID 28066325
- Enhanced Activity of Topical Hydrocortisone by Competitive Binding of Corticosteroid-Binding Globulin.
- Bodor ET1, Wu WM2, Chandran VR3, Bodor N2.
- Journal of pharmaceutical sciences.J Pharm Sci.2016 Sep;105(9):2873-8. doi: 10.1016/j.xphs.2016.03.028. Epub 2016 May 11.
- Atopic dermatitis of sensitive areas such as the face, particularly in children, is a difficult disease to treat as the standard therapeutic, topical steroids, is contraindicated for this application in children. Hydrocortisone (HC) can be used in these instances because it has been shown to be safe
- PMID 27179671
Japanese Journal
- Acute hepatotoxicity of DDT : Effect on glucocorticoid receptors and serum transcortin
- The Influence of Transcortin on Adrenocorticotropin-Stimulated Corticosterone Production in Monolayer Cultured Rat Adrenal Cells.
- Comparative study of primates' transcortin: Immunoreactivity and steroid-binding activity.
Related Links
- Transcortin, also known as corticosteroid-binding globulin (CBG) or serpin A6 is a protein that in humans is encoded by the SERPINA6 gene. It is an alpha- globulin. Contents. 1 Function; 2 Binding; 3 Synthesis; 4 Clinical significance; 5 See ...
Related Pictures
