Sex hormone-binding globulin
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Sex hormone-binding globulin
Available structures
PDB 1d2s, 1f5f, 1kdk, 1kdm, 1lhn, 1lho, 1lhu,
1lhv, 1lhw
Identifiers
Symbols SHBG; ABP; MGC126834; MGC138391
External OMIM: 182205 MGI: 98295 HomoloGene: 813
IDs
GeneCards: SHBG Gene
Molecular
function
Gene Ontology
• androgen binding
• protein binding
• lipid binding
• protein homodimerization
activity
• extracellular region
Cellular
component
Biological process • hormone transport
Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species
Human
Mouse
Entrez
6462
20415
Ensembl ENSG00000129214 ENSMUSG00000005202
UniProt P04278
RefSeq
Q5F214
NM_001040
XM_001006589
NP_001031
XP_001006589
(mRNA)
RefSeq
(protein)
Location Chr 17:
Chr 11:
(UCSC) 7.47 – 7.48 Mb
69.43 – 69.43 Mb
PubMed [1]
[2]
search
Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a
glycoprotein that binds to sex hormones, to be specific, testosterone and estradiol. Other steroid
hormones such as progesterone, cortisol, and other corticosteroids are bound by transcortin.
Contents
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1 Transport of sex hormones
2 SHBG production
3 Control
4 Blood values
5 Conditions with high or low levels
6 Measurement of sex hormones
7 See also
8 References
9 Further reading
[edit] 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 has a higher affinity for Dihydrotestosterone than for Testosterone or for
Estradiol, making it essential in women for regulating the bio-availability of
Dihydrotestosterone.
[edit] 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.
[edit] 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, whereas 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,[1][2] not any direct effect of insulin and specific genetic mechanisms that do this have been
found.
[edit] Blood values
Reference ranges for blood tests for SHBG have been estimated to be:[3]
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
[edit] 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.
[Cite]
[edit] Measurement of sex hormones
This section does not cite any references or sources. Please help improve this section by
adding citations to reliable sources. Unsourced material may be challenged and removed.
(December 2009)
When determining levels of circulating estradiol or testosterone, either a total measurement that
includes the "free" and the bound fractions could be done, 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.
[edit] See also

Androgen-binding protein
[edit] References
1.
2.
3.
^ "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.
^ 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.
^ Unit Code 91215 at Mayo Clinic Medical Laboratories. Retrieved April 2011
[edit] Further reading
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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 hormonebinding 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.
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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 hormonebinding 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:10.1158/10559965.EPI-08-0734. PMC 2660245. PMID 19064566