Transcortin Explained

Transcortin, also known as corticosteroid-binding globulin (CBG) or serpin A6, is a protein produced in the liver in animals. In humans it 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).^[3]

Binding

Transcortin binds several steroid hormones at high rates:

• Cortisol - Approximately 90% 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.
• Cortisone^[4]
• Deoxycorticosterone (DOC)
• 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.^[5]
• 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.^[6]
• 17α-Hydroxyprogesterone

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.

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, bound plasma cortisol in term pregnancy is approximately 2 to 3 times that of nonpregnant women.^{[10] [11]}

See also

• Serpin
• Circaseptan, 7-day biological cycle

Further reading

• Rosner W, Beers PC, Awan T, Khan MS . Identification of corticosteroid-binding globulin in human milk: measurement with a filter disk assay. . J. Clin. Endocrinol. Metab. . 42 . 6 . 1064–73 . 1976 . 932172 . 10.1210/jcem-42-6-1064 .
• Smith CL, Power SG, Hammond GL . 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 . 1992 . 1504007 . 10.1016/0960-0760(92)90107-T . 45601231 .
• Brotherton J . Cortisol and transcortin in human seminal plasma and amniotic fluid as estimated by modern specific assays. . Andrologia . 22 . 3 . 197–204 . 1990 . 2240617 . 10.1111/j.1439-0272.1990.tb01966.x . 2577211 . free .
• Underhill DA, Hammond GL . Organization of the human corticosteroid binding globulin gene and analysis of its 5'-flanking region. . Mol. Endocrinol. . 3 . 9 . 1448–54 . 1990 . 2608068 . 10.1210/mend-3-9-1448 . free .
• Loric S, Egloff M, Domingo M, etal . Immunochemical characterization of corticosteroid-binding globulin in human bronchoalveolar fluid. . Clin. Chim. Acta . 186 . 1 . 19–23 . 1990 . 2612005 . 10.1016/0009-8981(89)90198-8 .
• Heubner A, Belovsky O, Müller W, etal . Application of liquid-liquid partition chromatography in the simultaneous purification of sex-hormone-binding globulin and corticosteroid-binding globulin. . J. Chromatogr. . 397 . 419–34 . 1987 . 2821037 . 10.1016/S0021-9673(01)85027-5 .
• Kato EA, Hsu BR, Kuhn RW . Comparative structural analyses of corticosteroid binding globulin. . J. Steroid Biochem. . 29 . 2 . 213–20 . 1988 . 3347061 . 10.1016/0022-4731(88)90268-3 .
• Bardin CW, Gunsalus GL, Musto NA, etal . 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 . 1988 . 3386241 . 10.1016/0022-4731(88)90085-4 .
• Hammond GL, Langley MS . Identification and measurement of sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) in human saliva. . Acta Endocrinol. . 112 . 4 . 603–8 . 1986 . 3751467 . 10.1530/acta.0.1120603.
• Agrimonti F, Frairia R, Fornaro D, etal . Circadian and circaseptan rhythmicities in corticosteroid-binding globulin (CBG) binding activity of human milk. . Chronobiologia . 9 . 3 . 281–90 . 1983 . 7172869 .
• Misao R, Hori M, Ichigo S, etal . 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 . 1995 . 7734053 . 10.1051/rnd:19950204 . free .
• Misao R, Hori M, Ichigo S, etal . Corticosteroid-binding globulin mRNA levels in human uterine endometrium. . Steroids . 59 . 10 . 603–7 . 1995 . 7878688 . 10.1016/0039-128X(94)90055-8 . 24945362 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Avvakumov GV, Hammond GL . Glycosylation of human corticosteroid-binding globulin. Differential processing and significance of carbohydrate chains at individual sites. . Biochemistry . 33 . 19 . 5759–65 . 1994 . 8180202 . 10.1021/bi00185a012 .
• Van Baelen H, Power SG, Hammond GL . Decreased cortisol-binding affinity of transcortin Leuven is associated with an amino acid substitution at residue-93. . Steroids . 58 . 6 . 275–7 . 1993 . 8212073 . 10.1016/0039-128X(93)90072-U . 25160586 .
• Misao R, Nakanishi Y, Fujimoto J, etal . Expression of corticosteroid-binding globulin mRNA in human uterine endometrial cancers. . Steroids . 60 . 10 . 720–4 . 1996 . 8539782 . 10.1016/0039-128X(95)00106-Z . 37077783 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .

External links

• • The MEROPS online database for peptidases and their inhibitors: I04.954

Notes and References

1. Hammond GL, Smith CL, Goping IS, Underhill DA, Harley MJ, Reventos J, Musto NA, Gunsalus GL, Bardin CW . 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 . August 1987 . 3299377 . 298812 . 10.1073/pnas.84.15.5153 . 1987PNAS...84.5153H . free .
2. Byth BC, Billingsley GD, Cox DW . 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 . July 1994 . 7912884 . 1918218 .
3. Web site: Entrez Gene: SERPINA6 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6.
4. Book: E. Edward Bittar . Neville Bittar . Molecular and Cellular Endocrinology . 23 August 2012 . 1997 . Elsevier . 978-1-55938-815-3 . 238.
5. Book: Principles and Practice of Endocrinology and Metabolism . 23 August 2012 . 24 April 2001 . Lippincott Williams & Wilkins . 978-0-7817-1750-2 . 712.
6. Book: Negi . Introduction To Endocrinology . 23 August 2012 . 2009 . PHI Learning Pvt. Ltd. . 978-81-203-3850-0 . 268.
7. Dunn JF, Nisula BC, Rodbard D . 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 . July 1981 . 7195404 . 10.1210/jcem-53-1-58 . 23 August 2012 . 14 December 2019 . https://web.archive.org/web/20191214212905/http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=7195404 . dead .
8. Musa BU, Seal US, Doe RP . Elevation of certain plasma proteins in man following estrogen administration: a dose-response relationship . J. Clin. Endocrinol. Metab. . 25 . 9 . 1163–6 . September 1965 . 4284083 . 10.1210/jcem-25-9-1163 .
9. Torpy DJ, Lundgren BA, Ho JT, Lewis JG, Scott HS, Mericq V . CBG Santiago: a novel CBG mutation . J. Clin. Endocrinol. Metab. . 97 . 1 . E151–5 . January 2012 . 22013108 . 10.1210/jc.2011-2022 . free .
10. Book: Rosen MI, Shnider SM, Levinson G, Hughes . Shnider and Levinson's anesthesia for obstetrics . Lippincott Williams & Wilkins . Hagerstwon, MD . 2002 . 13 . 0-683-30665-0 .
11. Book: Ann M. Gronowski. Handbook of Clinical Laboratory Testing During Pregnancy. 6 May 2004. Springer Science & Business Media. 978-1-59259-787-1. 408–.