Transcortin

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).

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
• 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.
• 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.
• 17α-Hydroxyprogesterone

In addition, approximately 4% of serum testosterone is bound to transcortin. 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.

Clinical significance

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

References

References

1. (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.
2. (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.
3. "Entrez Gene: SERPINA6 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6".
4. (1997). "Molecular and Cellular Endocrinology". Elsevier.
5. (24 April 2001). "Principles and Practice of Endocrinology and Metabolism". Lippincott Williams & Wilkins.
6. Negi. (2009). "Introduction To Endocrinology". PHI Learning Pvt. Ltd..
7. (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.
8. (September 1965). "Elevation of certain plasma proteins in man following estrogen administration: a dose-response relationship". J. Clin. Endocrinol. Metab..
9. (January 2012). "CBG Santiago: a novel CBG mutation". J. Clin. Endocrinol. Metab..
10. Rosen MI, Shnider SM, Levinson G, Hughes. (2002). "Shnider and Levinson's anesthesia for obstetrics". Lippincott Williams & Wilkins.
11. Ann M. Gronowski. (6 May 2004). "Handbook of Clinical Laboratory Testing During Pregnancy". Springer Science & Business Media.