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Gene Review

SHBG  -  sex hormone-binding globulin

Homo sapiens

Synonyms: ABP, MGC126834, MGC138391, SBP, Sex hormone-binding globulin, ...
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Disease relevance of SHBG

  • RESULTS: No clear associations were found between the unadjusted levels of individual hormones or SHBG and the risk of prostate cancer [1].
  • Furthermore, SHBG alleles within the general population contain at least 6-10 TAAAA repeats, and the transcriptional activity of a human SHBG promoter-luciferase reporter construct containing 6 TAAAA repeats was significantly lower than for similar reporter constructs containing 7-10 TAAAA repeats when tested in human HepG2 hepatoblastoma cells [2].
  • Low SHBG levels may contribute to the menstrual disturbance seen in acromegaly in addition to any gonadotropin deficiency or hyperprolactinemia and may account for hirsutism in the presence of normal testosterone levels [3].
  • However, the independent negative correlation between GH and SHBG levels suggests that GH may, directly or indirectly, lead to a fall in SHBG, possibly determined by the hyperinsulinemia known to occur in acromegaly [3].
  • We investigated the prevalence of hypogonadism in type 2 diabetes by measuring serum total T, free T (FT), SHBG, LH, FSH, and prolactin (PRL) in 103 type 2 diabetes patients [4].
  • Dietary isoflavones are thought to reduce breast cancer risk by stimulating circulating sex hormone-binding globulin (SHBG) levels [5].

Psychiatry related information on SHBG


High impact information on SHBG


Chemical compound and disease context of SHBG


Biological context of SHBG

  • This apparent size difference is due in part to differences in glycosylation of plasma and acrosomal SHBG isoforms [18].
  • Little is known about SHBG gene expression in the human testis, but human SHBG transcripts accumulate in a spermatogenic stage-dependent manner in the testes of mice containing an 11-kb human SHBG transgene [18].
  • Remarkably, these mice express the modified human SHBG transgene in the testis as well as the liver [19].
  • This could influence the binding kinetics of 2-MeOE2 and/or facilitate ligand-dependent interactions between SHBG and other proteins [20].
  • These two disparate functions of SHBG, regulation of the concentration of free steroids in plasma and signal transduction in selected tissues, raise the question of how its synthesis and secretion might be regulated so as to best perform these two disparate functions [21].

Anatomical context of SHBG


Associations of SHBG with chemical compounds


Physical interactions of SHBG


Regulatory relationships of SHBG


Other interactions of SHBG

  • Clinical response was assessed monthly together with serum sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogens (E1, E2, and E1S), lipids, insulin-like growth factor-1 (IGF-1), and bone metabolites (CrossLaps CTx) [34].
  • CONCLUSION: This study is the first to demonstrate that targeting the TNF pathway can significantly decrease Lp(a) and homocysteine levels and elevate Apo A-I and SHBG concentrations [35].
  • Whether the action of the IGF/IGFBP system on bone metabolism is mediated partly through its effects on muscle mass or SHBG deserves further study [36].
  • We conclude that high levels of some biochemical markers of bone turnover, low serum estradiol, low DHEA sulfate, high SHBG, and high PTH are associated with increased risk of osteoporotic fracture in postmenopausal women, independently of each other and of BMD [37].
  • IGFBP-2 remained an independent negative predictor of BMD in men, postmenopausal women, and all women combined after additional adjustment for bioavailable sex steroids, but not at all sites after adjustment for SHBG and muscle mass [36].

Analytical, diagnostic and therapeutic context of SHBG

  • Western blots of germ cell extracts from these transgenic mice and from human sperm indicate that the immunoreactive human SHBG in the acrosome composes electrophoretic variants, which are 3-5 kDa smaller than the major electrophoretic isoforms of human SHBG in the blood [18].
  • In addition, in tissue sections of human prostate, we demonstrate the presence of SHBG (immunocytochemistry) and SHBG mRNA (in situ hybridization) [21].
  • The calcium supplemented (n = 15; age 60.9 +/- 9.4 years, body mass index [BMI] 33.2 +/- 4.6 kg/m2) and placebo (n = 16; age 55.8 +/- 8.3 years, BMI 32.9 +/- 4.5 kg/m2) groups lost similar amounts of weight over the study interval (10.2 +/- 5.3% vs. 10.0 +/- 5.2%) and both groups increased SHBG (p < 0.001) [38].
  • Although the relative abundance of the various SHBG-related mRNAs in the testis has not been established, Northern blot analysis indicates that they are similar in size (1.6 kb) to that of hepatic SHBG mRNA [39].
  • Sequence analysis of the gene indicates that the complete coding region for the SHBG precursor is comprised of 8 exons, which are distributed over 3.2 kilobase (kb) of genomic DNA, and the unique 5' regions associated with the two SHBG-related testicular cDNAs were identified 1.9 kb upstream from the initiating codon for SHBG [39].


  1. Prospective study of sex hormone levels and risk of prostate cancer. Gann, P.H., Hennekens, C.H., Ma, J., Longcope, C., Stampfer, M.J. J. Natl. Cancer Inst. (1996) [Pubmed]
  2. Human sex hormone-binding globulin promoter activity is influenced by a (TAAAA)n repeat element within an Alu sequence. Hogeveen, K.N., Talikka, M., Hammond, G.L. J. Biol. Chem. (2001) [Pubmed]
  3. Menstrual irregularity in women with acromegaly. Kaltsas, G.A., Mukherjee, J.J., Jenkins, P.J., Satta, M.A., Islam, N., Monson, J.P., Besser, G.M., Grossman, A.B. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  4. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. Dhindsa, S., Prabhakar, S., Sethi, M., Bandyopadhyay, A., Chaudhuri, A., Dandona, P. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  5. Implications of gene-environment interaction in studies of gene variants in breast cancer: an example of dietary isoflavones and the D356N polymorphism in the sex hormone-binding globulin gene. Low, Y.L., Dunning, A.M., Dowsett, M., Luben, R.N., Khaw, K.T., Wareham, N.J., Bingham, S.A. Cancer Res. (2006) [Pubmed]
  6. Serum concentrations of sex hormone binding globulin are elevated in kwashiorkor and anorexia nervosa but not in marasmus. Pascal, N., Amouzou, E.K., Sanni, A., Namour, F., Abdelmouttaleb, I., Vidailhet, M., Guéant, J.L. Am. J. Clin. Nutr. (2002) [Pubmed]
  7. Cross-sectional association between markers of inflammation and serum sex steroid levels in the postmenopausal estrogen/progestin interventions trial. Crandall, C., Palla, S., Reboussin, B., Hu, P., Barrett-Connor, E., Reuben, D., Greendale, G. Journal of women's health (2002) (2006) [Pubmed]
  8. Effect of smoking and smoking cessation on bone mass, bone remodeling, vitamin D, PTH and sex hormones. Supervia, A., Nogues, X., Enjuanes, A., Vila, J., Mellibovsky, L., Serrano, S., Aubia, J., Diez-Perez, A. Journal of musculoskeletal & neuronal interactions (2006) [Pubmed]
  9. Relationship between circulating levels of sex hormones and insulin-like growth factor-1 and fluid intelligence in older men. Aleman, A., de Vries, W.R., Koppeschaar, H.P., Osman-Dualeh, M., Verhaar, H.J., Samson, M.M., Bol, E., de Haan, E.H. Experimental aging research. (2001) [Pubmed]
  10. Sexual function and gonadal hormones in patients taking antipsychotic treatment for schizophrenia or schizoaffective disorder. Howes, O.D., Wheeler, M.J., Pilowsky, L.S., Landau, S., Murray, R.M., Smith, S. The Journal of clinical psychiatry (2007) [Pubmed]
  11. A naturally occurring epigenetic mutation in a gene encoding an SBP-box transcription factor inhibits tomato fruit ripening. Manning, K., Tör, M., Poole, M., Hong, Y., Thompson, A.J., King, G.J., Giovannoni, J.J., Seymour, G.B. Nat. Genet. (2006) [Pubmed]
  12. Dehydroepiandrosterone replacement in women with adrenal insufficiency. Arlt, W., Callies, F., van Vlijmen, J.C., Koehler, I., Reincke, M., Bidlingmaier, M., Huebler, D., Oettel, M., Ernst, M., Schulte, H.M., Allolio, B. N. Engl. J. Med. (1999) [Pubmed]
  13. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. Bunevicius, R., Kazanavicius, G., Zalinkevicius, R., Prange, A.J. N. Engl. J. Med. (1999) [Pubmed]
  14. Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin. Plymate, S.R., Matej, L.A., Jones, R.E., Friedl, K.E. J. Clin. Endocrinol. Metab. (1988) [Pubmed]
  15. Hyperinsulinemia and decreased insulin-like growth factor-binding protein-1 are common features in prepubertal and pubertal girls with a history of premature pubarche. Ibáñez, L., Potau, N., Zampolli, M., Riqué, S., Saenger, P., Carrascosa, A. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  16. Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive airways pressure therapy. Grunstein, R.R., Handelsman, D.J., Lawrence, S.J., Blackwell, C., Caterson, I.D., Sullivan, C.E. J. Clin. Endocrinol. Metab. (1989) [Pubmed]
  17. Sex hormone-binding globulin and insulin-like growth factor-binding protein-1 as indicators of metabolic syndrome, cardiovascular risk, and mortality in elderly men. Kalme, T., Seppälä, M., Qiao, Q., Koistinen, R., Nissinen, A., Harrela, M., Loukovaara, M., Leinonen, P., Tuomilehto, J. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  18. A human sex hormone-binding globulin isoform accumulates in the acrosome during spermatogenesis. Selva, D.M., Hogeveen, K.N., Seguchi, K., Tekpetey, F., Hammond, G.L. J. Biol. Chem. (2002) [Pubmed]
  19. Repression of the human sex hormone-binding globulin gene in Sertoli cells by upstream stimulatory transcription factors. Selva, D.M., Hogeveen, K.N., Hammond, G.L. J. Biol. Chem. (2005) [Pubmed]
  20. Crystal structure of human sex hormone-binding globulin in complex with 2-methoxyestradiol reveals the molecular basis for high affinity interactions with C-2 derivatives of estradiol. Avvakumov, G.V., Grishkovskaya, I., Muller, Y.A., Hammond, G.L. J. Biol. Chem. (2002) [Pubmed]
  21. Sex hormone-binding globulin in the human prostate is locally synthesized and may act as an autocrine/paracrine effector. Hryb, D.J., Nakhla, A.M., Kahn, S.M., St George, J., Levy, N.C., Romas, N.A., Rosner, W. J. Biol. Chem. (2002) [Pubmed]
  22. Estradiol activates the prostate androgen receptor and prostate-specific antigen secretion through the intermediacy of sex hormone-binding globulin. Nakhla, A.M., Romas, N.A., Rosner, W. J. Biol. Chem. (1997) [Pubmed]
  23. Diet and reproductive hormones: a study of vegetarian and nonvegetarian postmenopausal women. Armstrong, B.K., Brown, J.B., Clarke, H.T., Crooke, D.K., Hähnel, R., Masarei, J.R., Ratajczak, T. J. Natl. Cancer Inst. (1981) [Pubmed]
  24. Estrogen and sex hormone-binding globulin levels in nulliparous and parous women. Bernstein, L., Pike, M.C., Ross, R.K., Judd, H.L., Brown, J.B., Henderson, B.E. J. Natl. Cancer Inst. (1985) [Pubmed]
  25. Low sex hormone-binding globulin and testosterone levels in association with erectile dysfunction among human immunodeficiency virus-infected men receiving testosterone and oxandrolone. Wasserman, P., Segal-Maurer, S., Rubin, D. J. Sex. Med (2008) [Pubmed]
  26. Characterization of a cDNA coding for sex steroid-binding protein of human plasma. Que, B.G., Petra, P.H. FEBS Lett. (1987) [Pubmed]
  27. Sex hormone-binding globulin: not only a transport protein. What news is around the corner? Fortunati, N. J. Endocrinol. Invest. (1999) [Pubmed]
  28. 18F-labeled difluoroestradiols: preparation and preclinical evaluation as estrogen receptor-binding radiopharmaceuticals. Seimbille, Y., Rousseau, J., Bénard, F., Morin, C., Ali, H., Avvakumov, G., Hammond, G.L., van Lier, J.E. Steroids (2002) [Pubmed]
  29. Changes in systemic gonadal and adrenal steroids in asymptomatic human immunodeficiency virus-infected men: relationship with the CD4 cell counts. Laudat, A., Blum, L., Guéchot, J., Picard, O., Cabane, J., Imbert, J.C., Giboudeau, J. Eur. J. Endocrinol. (1995) [Pubmed]
  30. Ovarian electrocauterization causes LH-regulated but not insulin-regulated endocrine changes. Tiitinen, A., Tenhunen, A., Seppälä, M. Clin. Endocrinol. (Oxf) (1993) [Pubmed]
  31. Racial differences in prostate androgen levels in men with clinically localized prostate cancer. Mohler, J.L., Gaston, K.E., Moore, D.T., Schell, M.J., Cohen, B.L., Weaver, C., Petrusz, P. J. Urol. (2004) [Pubmed]
  32. Serum adiponectin and leptin levels in relation to the metabolic syndrome, androgenic profile and somatotropic axis in healthy non-diabetic elderly men. Gannagé-Yared, M.H., Khalife, S., Semaan, M., Fares, F., Jambart, S., Halaby, G. Eur. J. Endocrinol. (2006) [Pubmed]
  33. Observations on the role of GH/IGF-1 and sex hormone binding globulin (SHBG) in the pubertal development of growth hormone deficient (GHD) children. Rudd, B.T., Rayner, P.H., Thomas, P.H. Acta endocrinologica. Supplementum. (1986) [Pubmed]
  34. Comparison of the systemic and intratumoral effects of tamoxifen and the aromatase inhibitor vorozole in postmenopausal patients with primary breast cancer. Harper-Wynne, C.L., Sacks, N.P., Shenton, K., MacNeill, F.A., Sauven, P., Laidlaw, I.J., Rayter, Z., Miall, S., Howes, A., Salter, J., Hills, M.J., Lowe, F.M., A'Hern, R., Nasiri, N., Doody, D., Iqbal, J., Dowsett, M. J. Clin. Oncol. (2002) [Pubmed]
  35. Effects of tumor necrosis factor blockade on cardiovascular risk factors in psoriatic arthritis: a double-blind, placebo-controlled study. Sattar, N., Crompton, P., Cherry, L., Kane, D., Lowe, G., McInnes, I.B. Arthritis Rheum. (2007) [Pubmed]
  36. A potentially deleterious role of IGFBP-2 on bone density in aging men and women. Amin, S., Riggs, B.L., Atkinson, E.J., Oberg, A.L., Melton, L.J., Khosla, S. J. Bone Miner. Res. (2004) [Pubmed]
  37. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. Garnero, P., Sornay-Rendu, E., Claustrat, B., Delmas, P.D. J. Bone Miner. Res. (2000) [Pubmed]
  38. Calcium supplementation suppresses bone turnover during weight reduction in postmenopausal women. Ricci, T.A., Chowdhury, H.A., Heymsfield, S.B., Stahl, T., Pierson, R.N., Shapses, S.A. J. Bone Miner. Res. (1998) [Pubmed]
  39. The human sex hormone-binding globulin gene contains exons for androgen-binding protein and two other testicular messenger RNAs. Hammond, G.L., Underhill, D.A., Rykse, H.M., Smith, C.L. Mol. Endocrinol. (1989) [Pubmed]
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