Sex hormone-binding globulin - Wikipedia

Sex hormone-binding globulin - Wikipedia

Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to sex hormones, to be specific, androgens and estrogens. Other steroid hormones such as progesterone, cortisol, and other corticosteroids are bound by transcortin.

Contents 1 Transport of sex hormones 2 SHBG production 3 Control 4 Blood values 5 Conditions associated with high or low levels 6 Measurement of sex hormones 7 See also 8 References 9 Further reading

Transport of sex hormones

Testosterone and estradiol circulate in the bloodstream, bound mostly to SHBG and to a lesser extent serum albumin and corticosteroid-binding globulin (CBG) (AKA transcortin). Only a very small fraction of about 1-2% is unbound, or "free," and thus biologically active and able to enter a cell and activate its receptor. SHBG inhibits the function of these hormones. Thus, bioavailability of sex hormones is influenced by the level of SHBG. The binding affinity of sex steroids for SHBG is dihydrotestosterone (DHT) > testosterone > androstenediol > estradiol > estrone.^[1] DHEA is weakly bound to SHBG as well, but DHEA-S is not.^[1] Androstenedione is not bound to SHBG either, and is instead bound solely to albumin.^[2]

SHBG production

SHBG is produced mostly by the liver and is released into the bloodstream. Other sites that produce SHBG include the brain, uterus, testes, and placenta. Testes-produced SHBG is called androgen-binding protein. The gene for SHBG is located on chromosome 17.

Control

SHBG has both enhancing and inhibiting hormonal influences. It decreases with high levels of insulin, growth hormone, insulin-like growth factor 1 (IGF-1), androgens, prolactin and transcortin. High estrogen, and thyroxine cause it to increase.
Recent evidence suggests hepatic lipogenesis reduces SHBG, not insulin. Genetic corollaries to this mechanism have been identified.^[3][4]

Blood values

Reference ranges for blood tests for SHBG have been estimated to be:^[5]

Patient type	Range
Adult female, premenopausal	40 - 120 nmol/L
Adult female, postmenopausal	28 - 112 nmol/L
Adult male	20 - 60 nmol/L
Age 1 - 23 months	60 - 252 nmol/L
Prepubertal (24m - 8y)	72 - 220 nmol/L
Pubertal female	36 - 125 nmol/L
Pubertal male	16 - 100 nmol/L

Conditions associated with high or low levels

SHBG levels are decreased by androgens, anabolic steroids,^[6] polycystic ovary syndrome, hypothyroidism, diabetes, obesity, Cushing's syndrome, and acromegaly. SHBG levels increase with estrogenic states (oral contraceptives), pregnancy, hyperthyroidism, cirrhosis, anorexia nervosa, and certain drugs. Long-term calorie restriction of more than 50 percent increases SHBG, while lowering free and total testosterone and estradiol. DHEA-S, which lacks affinity for SHBG, is not affected by calorie restriction.^[7]

Measurement of sex hormones

When checking serum estradiol or testosterone, a total level that includes free and bound fractions can be assayed, or the free portion may be measured alone. A free androgen index expresses the ratio of testosterone to SHBG and can be used to summarize the activity of free testosterone. The total testosterone is likely the most accurate measurement of testosterone levels.^{[citation needed]} Sex hormone-binding globulin can be measured separate from the total fraction of testosterone.

See also

• Androgen-binding protein

References

1. ^ ^{a b} Somboonporn W, Davis SR (June 2004). "Testosterone effects on the breast: implications for testosterone therapy for women". Endocrine Reviews 25 (3): 374–88. doi:10.1210/er.2003-0016. PMID 15180949.
2. ^ Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. 24 April 2001. ISBN 978-0-7817-1750-2. Retrieved 4 August 2012.
3. ^ "Too much sugar turns off gene that controls the effects of sex steroids". PhysOrg.com. 2007-11-07. Retrieved 2008-02-10.
4. ^ Selva DM, Hogeveen KN, Innis SM, Hammond GL (2007). "Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone–binding globulin gene". J. Clin. Invest. 117 (12): 3979–87. doi:10.1172/JCI32249. PMC 2066187. PMID 17992261.
5. ^ Unit Code 91215 at Mayo Clinic Medical Laboratories. Retrieved April 2011
6. ^ Ruokonen A, Alén M, Bolton N, Vihko R (July 1985). "Response of serum testosterone and its precursor steroids, SHBG and CBG to anabolic steroid and testosterone self-administration in man". Journal of Steroid Biochemistry 23 (1): 33–8. PMID 3160892.
7. ^ Cangemi R, Friedmann AJ, Holloszy JO, Fontana L (April 2010). "Long-term effects of calorie restriction on serum sex-hormone concentrations in men". Aging Cell 9 (2): 236–42. doi:10.1111/j.1474-9726.2010.00553.x. PMID 20096034.

Further reading

• Hammond GL, Bocchinfuso WP (1996). "Sex hormone-binding globulin: gene organization and structure/function analyses". Horm. Res. 45 (3–5): 197–201. doi:10.1159/000184787. PMID 8964583.
• Rosner W, Hryb DJ, Khan MS, et al. (1999). "Sex hormone-binding globulin mediates steroid hormone signal transduction at the plasma membrane". J. Steroid Biochem. Mol. Biol. 69 (1–6): 481–5. doi:10.1016/S0960-0760(99)00070-9. PMID 10419028.
• Power SG, Bocchinfuso WP, Pallesen M, et al. (1992). "Molecular analyses of a human sex hormone-binding globulin variant: evidence for an additional carbohydrate chain". J. Clin. Endocrinol. Metab. 75 (4): 1066–70. doi:10.1210/jc.75.4.1066. PMID 1400872.
• Bérubé D, Séralini GE, Gagné R, Hammond GL (1991). "Localization of the human sex hormone-binding globulin gene (SHBG) to the short arm of chromosome 17 (17p12----p13)". Cytogenet. Cell Genet. 54 (1–2): 65–7. doi:10.1159/000132958. PMID 2249477.
• Gershagen S, Lundwall A, Fernlund P (1990). "Characterization of the human sex hormone binding globulin (SHBG) gene and demonstration of two transcripts in both liver and testis". Nucleic Acids Res. 17 (22): 9245–58. doi:10.1093/nar/17.22.9245. PMC 335128. PMID 2587256.
• Hammond GL, Underhill DA, Rykse HM, Smith CL (1990). "The human sex hormone-binding globulin gene contains exons for androgen-binding protein and two other testicular messenger RNAs". Mol. Endocrinol. 3 (11): 1869–76. doi:10.1210/mend-3-11-1869. PMID 2608061.
• Que BG, Petra PH (1987). "Characterization of a cDNA coding for sex steroid-binding protein of human plasma". FEBS Lett. 219 (2): 405–9. doi:10.1016/0014-5793(87)80261-2. PMID 2956125.
• Gershagen S, Fernlund P, Lundwall A (1987). "A cDNA coding for human sex hormone binding globulin. Homology to vitamin K-dependent protein S". FEBS Lett. 220 (1): 129–35. doi:10.1016/0014-5793(87)80890-6. PMID 2956126.
• Walsh KA, Titani K, Takio K, et al. (1987). "Amino acid sequence of the sex steroid binding protein of human blood plasma". Biochemistry 25 (23): 7584–90. doi:10.1021/bi00371a048. PMID 3542030.
• Hammond GL, Underhill DA, Smith CL, et al. (1987). "The cDNA-deduced primary structure of human sex hormone-binding globulin and location of its steroid-binding domain". FEBS Lett. 215 (1): 100–4. doi:10.1016/0014-5793(87)80121-7. PMID 3569533.
• Hammond GL, Robinson PA, Sugino H, et al. (1986). "Physicochemical characteristics of human sex hormone binding globulin: evidence for two identical subunits". J. Steroid Biochem. 24 (4): 815–24. doi:10.1016/0022-4731(86)90442-5. PMID 3702459.
• Hardy DO, Cariño C, Catterall JF, Larrea F (1995). "Molecular characterization of a genetic variant of the steroid hormone-binding globulin gene in heterozygous subjects". J. Clin. Endocrinol. Metab. 80 (4): 1253–6. doi:10.1210/jc.80.4.1253. PMID 7714097.
• Cargill M, Altshuler D, Ireland J, et al. (1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes". Nat. Genet. 22 (3): 231–8. doi:10.1038/10290. PMID 10391209.
• Grishkovskaya I, Avvakumov GV, Sklenar G, et al. (2000). "Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain". EMBO J. 19 (4): 504–12. doi:10.1093/emboj/19.4.504. PMC 305588. PMID 10675319.
• Hogeveen KN, Talikka M, Hammond GL (2001). "Human sex hormone-binding globulin promoter activity is influenced by a (TAAAA)n repeat element within an Alu sequence". J. Biol. Chem. 276 (39): 36383–90. doi:10.1074/jbc.M104681200. PMID 11473114.
• Hryb DJ, Nakhla AM, Kahn SM, et al. (2002). "Sex hormone-binding globulin in the human prostate is locally synthesized and may act as an autocrine/paracrine effector". J. Biol. Chem. 277 (29): 26618–22. doi:10.1074/jbc.M202495200. PMID 12015315.
• Raineri M, Catalano MG, Hammond GL, et al. (2002). "O-Glycosylation of human sex hormone-binding globulin is essential for inhibition of estradiol-induced MCF-7 breast cancer cell proliferation". Mol. Cell. Endocrinol. 189 (1–2): 135–43. doi:10.1016/S0303-7207(01)00725-0. PMID 12039072.
• Grishkovskaya I, Avvakumov GV, Hammond GL, Muller YA (2002). "Resolution of a disordered region at the entrance of the human sex hormone-binding globulin steroid-binding site". J. Mol. Biol. 318 (3): 621–6. doi:10.1016/S0022-2836(02)00169-9. PMID 12054810.
• Thompson DJ, Healey CS, Baynes C, Kalmyrzaev B, et al. (2008). "Identification of common variants in the SHBG gene affecting sex hormone binding globulin levels and breast cancer risk in postmenopausal women". Cancer Epidemiol Biomarkers Prev. 17 (12): 3490–8. doi:10.1158/1055-9965.EPI-08-0734. PMC 2660245. PMID 19064566.