Sex hormone-binding globulin

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Sex hormone-binding globulin
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM182205 MGI98295 HomoloGene813 ChEMBL: 3305 GeneCards: SHBG Gene
RNA expression pattern
PBB GE SHBG 215689 s at tn.png
More reference expression data
Species Human Mouse
Entrez 6462 20415
Ensembl ENSG00000129214 ENSMUSG00000005202
UniProt P04278 P97497
RefSeq (mRNA) NM_001040 NM_011367
RefSeq (protein) NP_001031 NP_035497
Location (UCSC) Chr 17:
7.52 – 7.54 Mb
Chr 11:
69.61 – 69.62 Mb
PubMed search [1] [2]

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.

Transport of sex hormones[edit]

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 relative binding affinity of various 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[edit]

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.


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.

In an effort to explain obesity-related reductions in SHBG, recent evidence suggests sugar or monosaccharide-induced hepatic lipogenesis, hepatic lipids in general, and cytokines like TNF-alpha and Interleukin reduce SHBG, whereas insulin does not. As an example anti-psoriatic drugs that inhibit TNF-alpha cause an increase in SHBG. The common downstream mechanism for all of these, including the effect of thyroid hormones[3] was downregulation of HNF4, hepatocyte nuclear factor 4.[4][5][6][7][8]

Blood values[edit]

Reference ranges for blood tests for SHBG have been estimated to be:[9]

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[edit]

SHBG levels are decreased by androgens, administration of anabolic steroids,[10] 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.[11] Polycystic Ovarian Syndrome is associated with insulin resistance and excess insulin lowers SHBG, which increases free testosterone levels.

Measurement of sex hormones[edit]

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[edit]


  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. ^ Selva DM, Hammond GL (July 2009). "Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4alpha". J. Mol. Endocrinol. 43 (1): 19–27. doi:10.1677/JME-09-0025. PMID 19336534. 
  4. ^ "Too much sugar turns off gene that controls the effects of sex steroids". 2007-11-07. Retrieved 2008-02-10. 
  5. ^ 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. 
  6. ^ Simó R, Barbosa-Desongles A, Hernandez C, Selva DM (November 2012). "IL1β down-regulation of sex hormone-binding globulin production by decreasing HNF-4α via MEK-1/2 and JNK MAPK pathways". Mol. Endocrinol. 26 (11): 1917–27. doi:10.1210/me.2012-1152. PMID 22902540. 
  7. ^ Simó R, Barbosa-Desongles A, Lecube A, Hernandez C, Selva DM (February 2012). "Potential role of tumor necrosis factor-α in downregulating sex hormone-binding globulin". Diabetes 61 (2): 372–82. doi:10.2337/db11-0727. PMC 3266423. PMID 22210320. 
  8. ^ Goto A, Morita A, Goto M, Sasaki S, Miyachi M, Aiba N, Terauchi Y, Noda M, Watanabe S (2012). "Associations of sex hormone-binding globulin and testosterone with diabetes among men and women (the Saku Diabetes study): a case control study". Cardiovasc Diabetol 11: 130. doi:10.1186/1475-2840-11-130. PMC 3537568. PMID 23066943. 
  9. ^ Unit Code 91215 at Mayo Clinic Medical Laboratories. Retrieved April 2011
  10. ^ 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. 
  11. ^ 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[edit]