Transcortin

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Orthologs
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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.[1][2][3]

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.[3]

Binding

Transcortin binds several steroid hormones at high rates:

In addition, approximately 4% of serum testosterone is bound to transcortin.[7] 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.[8]

Clinical significance

Mutations in this gene are rare. Only four mutations have been described, often in association with fatigue and chronic pain.[9] 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.[10]

See also

References

  1. Hammond GL, Smith CL, Goping IS, Underhill DA, Harley MJ, Reventos J, Musto NA, Gunsalus GL, Bardin CW (August 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  2. Byth BC, Billingsley GD, Cox DW (July 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  3. 3.0 3.1 "Entrez Gene: SERPINA6 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6".<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  4. 4.0 4.1 4.2 E. Edward Bittar; Neville Bittar (1997). Molecular and Cellular Endocrinology. Elsevier. p. 238. ISBN 978-1-55938-815-3. Retrieved 23 August 2012.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  5. 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  6. Negi (2009). Introduction To Endocrinology. PHI Learning Pvt. Ltd. p. 268. ISBN 978-81-203-3850-0. Retrieved 23 August 2012.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  7. 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  8. 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  9. 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  10. 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>

Further reading

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  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>

External links