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Sex hormone-binding globulin

PDB rendering based on 1d2s.[1]
Available structures
1d2s, 1f5f, 1kdk, 1kdm, 1lhn, 1lho, 1lhu, 1lhv, 1lhw
Identifiers
Symbols SHBG; ABP; MGC126834; MGC138391
External IDs OMIM182205 MGI98295 HomoloGene813 GeneCards: SHBG Gene
RNA expression pattern
PBB GE SHBG 215689 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 6462 20415
Ensembl ENSG00000129214 ENSMUSG00000005202
UniProt P04278 Q5F214
RefSeq (mRNA) NM_001040 XM_001006589
RefSeq (protein) NP_001031 XP_001006589
Location (UCSC) Chr 17:
7.47 - 7.48 Mb
Chr 11:
69.43 - 69.43 Mb
PubMed search [1] [2]

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.

Contents

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. 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) (see:milk). Also, high androgen and transcortin levels decrease SHBG, while high growth hormone, estrogen and thyroxine levels increase it.

However, recent evidence suggests that it is the liver's production of fats that reduces SHBG levels, [2][3] 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 summarize 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

References

  1. ^ Grishkovskaya I, Avvakumov GV, Sklenar G, Dales D, Hammond GL, Muller YA (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. PMID 10675319.  
  2. ^ "Too much sugar turns off gene that controls the effects of sex steroids". PhysOrg.com. 2007-11-07. http://www.physorg.com/news113902673.html. Retrieved 2008-02-10.  
  3. ^ 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. PMID 17992261.  

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. 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. 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. PMID 19064566.  









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