Sex hormone-binding globulin

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Sex hormone-binding globulin (SHBG) is a glycoprotein that binds to sex hormones, specifically testosterone and estradiol. Other steroid hormones such as progesterone, cortisol, and other corticosteroids are bound by transcortin.

Transport of sex hormones

Testosterone and estradiol circulate in the bloodstream, bound mostly to SHBG and to some degree bound to serum albumin. Only a small fraction is unbound, or "free," and thus biologically active and able to enter a cell and activate its receptor. The SHBG inhibits the function of these hormones. Thus bioavailability of sex hormones is influenced by the level of SHBG.

SHBG production

SHBG is produced by the liver cells and is released into the bloodstream. Other sites that produce SHBG are the brain, uterus, and placenta and vagina. In addition SHBG is produced by the testes; testes-produced SHBG is also called androgen-binding protein. The gene for SHBG is located on chromosome 17.

Control

SHBG levels appear to be controlled by a delicate balance of enhancing and inhibiting factors. Its level is decreased by high levels of insulin and insulin-like growth factor 1 (IGF-1). Also, high androgen levels decrease SHBG, while high estrogen and thyroxine levels increase it.

However, recent evidence suggests that it is the liver's production of fats that reduces SHBG levels, not any direct effect of insulin and specific genetic mechanisms have been found that do this.

Conditions with high or low levels

Conditions with low SHBG include polycystic ovary syndrome, diabetes, and hypothyroidism. Conditions with high SHBG include pregnancy, hyperthyroidism, and anorexia nervosa. There has recently been research to link high SHBG levels with breast and testicular cancer as well.

Measurement of sex hormones

When determining levels of circulating estradiol or testosterone, either a total measurement could be done that includes the "free" and the bound fractions, or only the "free" hormone could be measured. A free androgen index expresses the ratio of testosterone to the sex hormone binding globulin and can be used to summarise the activity of free testosterone.

The total testosterone is likely the most accurate measurement of testosterone levels and should always be measured at 8 o'clock in the morning. Sex hormone binding globulin can be measured separate from the total fraction of testosterone.

See also

• Androgen binding protein

Further reading

• Hammond GL, Bocchinfuso WP (1996). Sex hormone-binding globulin: gene organization and structure/function analyses. Horm. Res. 45 (3-5): 197–201.
• 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.
• 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.
• 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.
• 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.
• 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.
• Que BG, Petra PH (1987). Characterization of a cDNA coding for sex steroid-binding protein of human plasma. FEBS Lett. 219 (2): 405–9.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

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