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.[5][6][7]
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.[7]
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]
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.[9]
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.[10]
In addition, approximately 4% of serum testosterone is bound to transcortin.[11] A similarly small fraction of serum estradiol is bound to transcortin as well.[citation needed]
Mutations in this gene are rare. Only four mutations have been described, often in association with fatigue and chronic pain.[13] 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.[14]
^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. PMID4284083.
^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. PMID22013108.
^Rosen MI, Shnider SM, Levinson G, Hughes (2002). Shnider and Levinson's anesthesia for obstetrics. Hagerstwon, MD: Lippincott Williams & Wilkins. p. 13. ISBN0-683-30665-0.{{cite book}}: CS1 maint: multiple names: authors list (link)
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. PMID932172.
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. PMID1504007.
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. PMID2240617.
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. PMID2253941.
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. PMID2608068.
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. PMID2612005.
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. PMID2821037.
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. PMID3386241.
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. PMID3751467.
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. PMID7172869.
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. PMID7734053.
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. PMID7878688.
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. PMID8125298.
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. PMID8180202.
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. PMID8212073.
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. PMID8539782.
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. PMID9373149.