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Gene Review

SHBG  -  sex hormone-binding globulin

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Disease relevance of SHBG


High impact information on SHBG

  • Moreover, the LWF diet significantly increased plasma SHBG, suggesting that the divergent effects of substituting LWF for other animal-protein sources on plasma cholesterol and lipoproteins may be partly mediated by variations in plasma sex-hormone status [2].
  • They are mosaic proteins possessing a carboxyl-terminal region presenting sequence similarity with plasma sex hormone binding globulin (plasma SHBG), although apparently not involved in steroid binding [3].
  • This module is followed by the thrombin-sensitive region (TSR), sensitive to thrombin cleavage, four epidermal growth factor (EGF)-like modules and a last region referred to as the sex hormone binding globulin (SHBG) domain [4].
  • Affinity purified antibodies to human sex hormone binding globulin (SHBG) were used in screening a human liver cDNA library, constructed in the expression vector lambda gt11 [5].
  • Confirmation that the cDNA clone represented human SHBG was obtained by the finding of a complete agreement in amino acid sequence with several peptide fragments generated from purified SHBG by proteolytic cleavage [5].

Biological context of SHBG

  • Serum SHBG concentrations were unchanged during postpartum anoestrus and over the oestrous cycle, as well as in pregnant animals [6].
  • The serum SHBG concentrations were about double those found in women with normal menstrual cycles, whereas oestradiol concentrations were much lower [6].
  • Structural modifications at C-17 of a steroid molecule involving esterification, epimerization or reduction of the 17 beta-hydroxyl group, or introduction of a bulky 17 alpha group have the effect of decreasing the SHBG binding affinity of the steroid molecule [7].
  • These studies show that SHBG is depressed in girls with premature adrenarche; with the increased testosterone levels, this results in a markedly elevated free androgen index, a measure of testosterone which is bioavailable to target tissue [8].
  • Serum sex hormone-binding globulin (SHBG) concentrations were of the same magnitude as in control cows during their estrous cycles [9].

Anatomical context of SHBG


Associations of SHBG with chemical compounds

  • Bovine steroid hormone and SHBG concentrations postpartum and during the oestrous cycle [6].
  • Differentiation between steroid hormone receptors CBG and SHBG in human target organ extracts by a single-step assay [10].
  • SHBG binding affinities, relative to the reference hormone 5 alpha-dihydrotestosterone, were estimated for the compounds [7].
  • The results demonstrate that binding of steroid hormones to SHBG is facilitated by the 17 beta-hydroxyl group, possibly involving hydrogen binding, and by the methyl group at C-19 of the steroid moiety [7].
  • Mean levels of steroids measured were elevated, and SHBG significantly depressed, in the girls with PA, with values (mean +/- SE) for DHEA-S (1.73 +/- 0.17 vs 0.25 +/- 0.06 mumol/l), 5-ADIOL-S (104 +/- 8 vs 31 +/- 4 nmol/l), AD (0.89 +/- 0.06 vs 0.62 +/- 0.04 nmol/l), and T (0.49 +/- 0.03 vs 0.23 +/- 0.06 nmol/l) [8].

Analytical, diagnostic and therapeutic context of SHBG


  1. Estradiol induction of cAMP in breast cancer cells is mediated by foetal calf serum (FCS) and sex hormone-binding globulin (SHBG). Fortunati, N., Fissore, F., Fazzari, A., Piovano, F., Catalano, M.G., Becchis, M., Berta, L., Frairia, R. J. Steroid Biochem. Mol. Biol. (1999) [Pubmed]
  2. Effects on plasma lipoproteins and endogenous sex hormones of substituting lean white fish for other animal-protein sources in diets of postmenopausal women. Jacques, H., Noreau, L., Moorjani, S. Am. J. Clin. Nutr. (1992) [Pubmed]
  3. SHBG region of the anticoagulant cofactor protein S: secondary structure prediction, circular dichroism spectroscopy, and analysis of naturally occurring mutations. Villoutreix, B.O., García de Frutos, P., Lövenklev, M., Linse, S., Fernlund, P., Dahlbäck, B. Proteins (1997) [Pubmed]
  4. A theoretical model for the Gla-TSR-EGF-1 region of the anticoagulant cofactor protein S: from biostructural pathology to species-specific cofactor activity. Villoutreix, B.O., Teleman, O., Dahlbäck, B. J. Comput. Aided Mol. Des. (1997) [Pubmed]
  5. A cDNA coding for human sex hormone binding globulin. Homology to vitamin K-dependent protein S. Gershagen, S., Fernlund, P., Lundwall, A. FEBS Lett. (1987) [Pubmed]
  6. Bovine steroid hormone and SHBG concentrations postpartum and during the oestrous cycle. Vesanen, M., Isomaa, V., Bolton, N.J., Alanko, M., Vihko, R. Acta Vet. Scand. (1990) [Pubmed]
  7. Binding of steroid hormones and anabolic agents to bovine sex-hormone binding globulin. Shrimanker, K., Salter, L.J., Patterson, R.L. Horm. Metab. Res. (1985) [Pubmed]
  8. Serum 5-androstene-3 beta,17 beta-diol sulphate, sex hormone binding globulin and free androgen index in girls with premature adrenarche. Montalto, J., Yong, A.B., Funder, J.W., Connelly, J.F. J. Steroid Biochem. (1989) [Pubmed]
  9. Bovine uterine, cervical and ovarian cytosol estrogen and progesterone receptor concentrations in cystic ovarian disease. Vesanen, M. Acta Vet. Scand. (1993) [Pubmed]
  10. Differentiation between steroid hormone receptors CBG and SHBG in human target organ extracts by a single-step assay. Wagner, R.K., Jungblut, P.W. Mol. Cell. Endocrinol. (1975) [Pubmed]
  11. Steroid-binding proteins in follicular fluid and peripheral plasma from pigs, cows and sheep. Cook, B., Hunter, R.H., Kelly, A.S. J. Reprod. Fertil. (1977) [Pubmed]
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