Genomes and Genes
sex hormone binding globulin
Gene Symbol: sex hormone binding globulin
Description: sex hormone binding globulin
Alias: ABP, SBP, TEBG, sex hormone-binding globulin, sex steroid-binding protein, testis-specific androgen-binding protein, testosterone-binding beta-globulin, testosterone-estradiol-binding globulin, testosterone-estrogen-binding globulin
Products: sex hormone binding globulin
- Hammond G, Underhill D, Rykse H, Smith C. The human sex hormone-binding globulin gene contains exons for androgen-binding protein and two other testicular messenger RNAs. Mol Endocrinol. 1989;3:1869-76 pubmed..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. ..
- Walsh K, Titani K, Takio K, Kumar S, Hayes R, Petra P. Amino acid sequence of the sex steroid binding protein of human blood plasma. Biochemistry. 1986;25:7584-90 pubmedThe amino acid sequence of the sex steroid binding protein (SBP) from human plasma has been determined. The SBP subunit consists of a 373-residue polypeptide chain containing two disulfide bonds and three oligosaccharide chains...
- Hammond G, Bocchinfuso W. Sex hormone-binding globulin: gene organization and structure/function analyses. Horm Res. 1996;45:197-201 pubmedHuman plasma sex hormone-binding globulin (SHBG) and testicular androgen-binding protein (ABP) are homodimeric glycoproteins with a single steroid-binding site...
- Laaksonen D, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen T, Valkonen V, et al. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care. 2004;27:1036-41 pubmed..Thus, hypoandrogenism is an early marker for disturbances in insulin and glucose metabolism that may progress to the metabolic syndrome or frank diabetes and may contribute to their pathogenesis. ..
- Kupelian V, Page S, Araujo A, Travison T, Bremner W, McKinlay J. Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J Clin Endocrinol Metab. 2006;91:843-50 pubmed..Together, these results suggest that low SHBG and/or AD may provide early warning signs for cardiovascular risk and an opportunity for early intervention in nonobese men. ..
- Thompson D, Healey C, Baynes C, Kalmyrzaev B, Ahmed S, Dowsett M, et al. 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. 2008;17:3490-8 pubmed publisher..rs6257 is a potential breast cancer susceptibility variant, but relationships between the genetic determinants of SHBG levels and breast cancer are complex. ..
- Onat A, Hergenc G, Karabulut A, Albayrak S, Can G, Kaya Z. Serum sex hormone-binding globulin, a determinant of cardiometabolic disorders independent of abdominal obesity and insulin resistance in elderly men and women. Metabolism. 2007;56:1356-62 pubmed..Low SHBG may be an important independent factor for cardiometabolic risk, particularly in women. ..
- Herbert Z, Göthe S, Caldwell J, Bernstein H, Melle C, von Eggeling F, et al. Identification of sex hormone-binding globulin in the human hypothalamus. Neuroendocrinology. 2005;81:287-93 pubmed..The multiple localizations of SHBG suggest neurohypophyseal and neuroendocrine functions. The biochemical data suggest that CSF SHBG is of brain rather than blood origin. ..
- Selva D, Hogeveen K, Seguchi K, Tekpetey F, Hammond G. A human sex hormone-binding globulin isoform accumulates in the acrosome during spermatogenesis. J Biol Chem. 2002;277:45291-8 pubmed..This is the first demonstration that human SHBG transcripts encode an SHBG isoform that remains within a cellular compartment. ..
- Eriksson A, Lorentzon M, Mellstrom D, Vandenput L, Swanson C, Andersson N, et al. SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density. J Clin Endocrinol Metab. 2006;91:5029-37 pubmed..Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men. ..
- Kataoka N, Cai Q, Xu W, Xiang Y, Cai H, Zheng W, et al. Association of endometrial cancer risk with a functional polymorphism (Asp(327)Asn) in the sex hormone-binding globulin gene. Cancer. 2007;109:1296-302 pubmed..The current results suggested that the codon 327 Asn allele in the SHBG gene may be related to a reduced risk of endometrial cancer among postmenopausal women. ..
- Bonnet F, Balkau B, Malécot J, Picard P, Lange C, Fumeron F, et al. Sex hormone-binding globulin predicts the incidence of hyperglycemia in women: interactions with adiponectin levels. Eur J Endocrinol. 2009;161:81-5 pubmed publisher..These findings suggest that a low SHBG level is a strong risk marker for dysglycemia in women, independently of both adiponectinemia and insulinemia. SHBG may therefore improve the identification of women at risk of diabetes. ..
- Berube D, Seralini G, Gagne R, Hammond G. Localization of the human sex hormone-binding globulin gene (SHBG) to the short arm of chromosome 17 (17p12----p13). Cytogenet Cell Genet. 1990;54:65-7 pubmed..In this way, the SHBG gene has been localized to the p12----p13 bands of chromosome 17. ..
- Selva D, Hammond G. Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4alpha. J Mol Endocrinol. 2009;43:19-27 pubmed publisher....
- Gershagen S, Lundwall A, Fernlund P. Characterization of the human sex hormone binding globulin (SHBG) gene and demonstration of two transcripts in both liver and testis. Nucleic Acids Res. 1989;17:9245-58 pubmedA genomic cosmid clone for human sex hormone binding globulin (SHBG), a liver-secreted plasma glycoprotein that binds sex steroids, was isolated with a previously characterized liver cDNA as probe...
- Ferk P, Teran N, Gersak K. The (TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG levels in women with polycystic ovary syndrome. Hum Reprod. 2007;22:1031-6 pubmed..3%) and control (33.1%) groups of patients. The (TAAAA)(n) SHBG gene polymorphism might be an important predictor for serum SHBG levels and, consequently, for hyperandrogenaemic clinical presentation of PCOS. ..
- Abrahamson P, Tworoger S, Aiello E, Bernstein L, Ulrich C, Gilliland F, et al. Associations between the CYP17, CYPIB1, COMT and SHBG polymorphisms and serum sex hormones in post-menopausal breast cancer survivors. Breast Cancer Res Treat. 2007;105:45-54 pubmed..These results provide little evidence that the CYP17, CYP1B1, and COMT polymorphisms are associated with different sex hormone levels in post-menopausal breast cancer survivors. ..
- Perry J, Weedon M, Langenberg C, Jackson A, Lyssenko V, Sparsø T, et al. Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes. Hum Mol Genet. 2010;19:535-44 pubmed publisherEpidemiological studies consistently show that circulating sex hormone binding globulin (SHBG) levels are lower in type 2 diabetes patients than non-diabetic individuals, but the causal nature of this association is controversial...
- Hammond G. Diverse roles for sex hormone-binding globulin in reproduction. Biol Reprod. 2011;85:431-41 pubmed publisher..The present review compares the production and functions of SHBG in different species and its diverse effects on reproduction. ..
- Simo R, Barbosa Desongles A, Lecube A, Hernandez C, Selva D. Potential role of tumor necrosis factor-? in downregulating sex hormone-binding globulin. Diabetes. 2012;61:372-82 pubmed publisher..Our results suggest that TNF-? plays an important role downregulating SHBG in chronic low-grade inflammatory diseases such as obesity and type 2 diabetes. ..
- Grishkovskaya I, Avvakumov G, Sklenar G, Dales D, Hammond G, Muller Y. Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain. EMBO J. 2000;19:504-12 pubmed..In all other jellyroll proteins, this loop is well ordered. If modelled accordingly, it covers the steroid-binding site and could thereby regulate access of ligands to the binding pocket. ..
- Jayagopal V, Kilpatrick E, Jennings P, Holding S, Hepburn D, Atkin S. The biological variation of sex hormone-binding globulin in type 2 diabetes: implications for sex hormone-binding globulin as a surrogate marker of insulin resistance. Diabetes Care. 2004;27:278-80 pubmed
- Cousin P, Calemard Michel L, Lejeune H, Raverot G, Yessaad N, Emptoz Bonneton A, et al. Influence of SHBG gene pentanucleotide TAAAA repeat and D327N polymorphism on serum sex hormone-binding globulin concentration in hirsute women. J Clin Endocrinol Metab. 2004;89:917-24 pubmed....
- Hammond G, Underhill D, Smith C, Goping I, Harley M, Musto N, et al. The cDNA-deduced primary structure of human sex hormone-binding globulin and location of its steroid-binding domain. FEBS Lett. 1987;215:100-4 pubmed..The library was screened with a radiolabeled rat androgen-binding protein (ABP) cDNA, and the abundance of SHBG cDNAs was 1 in 750,000 plaques examined...
- Li C, Ford E, Li B, Giles W, Liu S. Association of testosterone and sex hormone-binding globulin with metabolic syndrome and insulin resistance in men. Diabetes Care. 2010;33:1618-24 pubmed publisher..Low concentrations of total testosterone and SHBG were strongly associated with increased likelihood of having metabolic syndrome, independent of traditional cardiovascular risk factors and insulin resistance. ..
- Chubb S, Hyde Z, Almeida O, Flicker L, Norman P, Jamrozik K, et al. Lower sex hormone-binding globulin is more strongly associated with metabolic syndrome than lower total testosterone in older men: the Health in Men Study. Eur J Endocrinol. 2008;158:785-92 pubmed publisher..Further studies should examine whether measures that raise SHBG protect against the development of metabolic syndrome in older men. ..
- Rosner W, Hryb D, Khan M, Nakhla A, Romas N. Sex hormone-binding globulin mediates steroid hormone signal transduction at the plasma membrane. J Steroid Biochem Mol Biol. 1999;69:481-5 pubmed..These and other downstream effects of this system are reviewed. ..
- Que B, Petra P. Characterization of a cDNA coding for sex steroid-binding protein of human plasma. FEBS Lett. 1987;219:405-9 pubmed..clone previously isolated by screening a Charon 21A human liver cDNA library with rat androgen binding protein (ABP) cDNA...
- Hogeveen K, Talikka M, Hammond G. Human sex hormone-binding globulin promoter activity is influenced by a (TAAAA)n repeat element within an Alu sequence. J Biol Chem. 2001;276:36383-90 pubmed..Thus, a (TAAAA)(n) element within the human SHBG promoter influences transcriptional activity in HepG2 cells and may contribute to differences in plasma SHBG levels between individuals. ..
- Le T, Nestler J, Strauss J, Wickham E. Sex hormone-binding globulin and type 2 diabetes mellitus. Trends Endocrinol Metab. 2012;23:32-40 pubmed publisher..Taken together, these data provide support for an expanded role of SHBG in the pathophysiology of insulin resistance and T2DM. ..
- Hryb D, Nakhla A, Kahn S, St George J, Levy N, Romas N, et al. Sex hormone-binding globulin in the human prostate is locally synthesized and may act as an autocrine/paracrine effector. J Biol Chem. 2002;277:26618-22 pubmed..These observations are consistent with the hypothesis that SHBG, destined to participate in signaling at the cell membrane, is locally regulated and produced. ..
- Berndt S, Chatterjee N, Huang W, Chanock S, Welch R, Crawford E, et al. Variant in sex hormone-binding globulin gene and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev. 2007;16:165-8 pubmed..34; 95% confidence interval, 1.10-1.63; P = 0.0007). This study suggests that genetic variation in SHBG may influence prostate cancer susceptibility. ..
- Hammes A, Andreassen T, Spoelgen R, Raila J, Hubner N, Schulz H, et al. Role of endocytosis in cellular uptake of sex steroids. Cell. 2005;122:751-62 pubmedAndrogens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion...
- Garcia Closas M, Brinton L, Lissowska J, Richesson D, Sherman M, Szeszenia Dabrowska N, et al. Ovarian cancer risk and common variation in the sex hormone-binding globulin gene: a population-based case-control study. BMC Cancer. 2007;7:60 pubmed..These data do not support a substantial association between common genetic variation in SHBG and ovarian cancer risk. ..
- Selva D, Hogeveen K, Innis S, Hammond G. Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene. J Clin Invest. 2007;117:3979-87 pubmed..This provides a biological explanation for why SHBG is a sensitive biomarker of the metabolic syndrome and the metabolic disturbances associated with increased fructose consumption. ..
- Peter A, Kantartzis K, Machann J, Schick F, Staiger H, Machicao F, et al. Relationships of circulating sex hormone-binding globulin with metabolic traits in humans. Diabetes. 2010;59:3167-73 pubmed publisher..18). Possible mechanisms by which high circulating SHBG prevents the development of type 2 diabetes involve regulation of fasting glycemia but not alteration of insulin secretory function. ..
- Selva D, Hammond G. Peroxisome-proliferator receptor gamma represses hepatic sex hormone-binding globulin expression. Endocrinology. 2009;150:2183-9 pubmed publisher..We conclude that PPARgamma represses human SHBG expression in liver cells, and that differences in PPARgamma levels and activity contribute directly to variations in plasma SHBG levels. ..
- Dunning A, Dowsett M, Healey C, Tee L, Luben R, Folkerd E, et al. Polymorphisms associated with circulating sex hormone levels in postmenopausal women. J Natl Cancer Inst. 2004;96:936-45 pubmed..Genetic variation in CYP19 and SHBG contributes to variance in circulating hormone levels between postmenopausal women, but low r2 values may explain why these genes have given inconclusive results in breast cancer case-control studies. ..
- Fortunati N, Catalano M, Boccuzzi G, Frairia R. Sex Hormone-Binding Globulin (SHBG), estradiol and breast cancer. Mol Cell Endocrinol. 2010;316:86-92 pubmed publisher....
- Ohlsson C, Wallaschofski H, Lunetta K, Stolk L, Perry J, Koster A, et al. Genetic determinants of serum testosterone concentrations in men. PLoS Genet. 2011;7:e1002313 pubmed publisher..rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation. ..
- Goto A, Song Y, Chen B, Manson J, Buring J, Liu S. Coffee and caffeine consumption in relation to sex hormone-binding globulin and risk of type 2 diabetes in postmenopausal women. Diabetes. 2011;60:269-75 pubmed publisher..Our findings suggest that SHBG may account for the inverse association between coffee consumption and type 2 diabetes risk among postmenopausal women. ..
- Lormeau C, Soudan B, D Herbomez M, Pigny P, Duquesnoy B, Cortet B. Sex hormone-binding globulin, estradiol, and bone turnover markers in male osteoporosis. Bone. 2004;34:933-9 pubmed..Finally, our findings are in agreement with previous studies which suggest that serum SHBG is a new biological marker of fracture risk in men. ..
- Xita N, Tsatsoulis A. Genetic variants of sex hormone-binding globulin and their biological consequences. Mol Cell Endocrinol. 2010;316:60-5 pubmed publisher..However, the weight of evidence suggests that some common genetic variants of SHBG may influence SHBG levels and in part contribute to the phenotypic expression of human diseases. ..
- Pinós T, Barbosa Desongles A, Hurtado A, Santamaria Martínez A, de Torres I, Morote J, et al. Identification, characterization and expression of novel Sex Hormone Binding Globulin alternative first exons in the human prostate. BMC Mol Biol. 2009;10:59 pubmed publisherThe human Sex Hormone Binding Globulin (SHBG) gene, located at 17p13.1, comprises, at least, two different transcription units regulated by two different promoters...
- Haiman C, Riley S, Freedman M, Setiawan V, Conti D, Le Marchand L. Common genetic variation in the sex steroid hormone-binding globulin (SHBG) gene and circulating shbg levels among postmenopausal women: the Multiethnic Cohort. J Clin Endocrinol Metab. 2005;90:2198-204 pubmed....
- Xita N, Tsatsoulis A, Chatzikyriakidou A, Georgiou I. Association of the (TAAAA)n repeat polymorphism in the sex hormone-binding globulin (SHBG) gene with polycystic ovary syndrome and relation to SHBG serum levels. J Clin Endocrinol Metab. 2003;88:5976-80 pubmed....
- Nakhla A, Hryb D, Rosner W, Romas N, Xiang Z, Kahn S. Human sex hormone-binding globulin gene expression- multiple promoters and complex alternative splicing. BMC Mol Biol. 2009;10:37 pubmed publisher....
- Ding E, Song Y, Manson J, Hunter D, Lee C, Rifai N, et al. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med. 2009;361:1152-63 pubmed publisher..The clinical usefulness of both SHBG genotypes and plasma levels in stratification and intervention for the risk of type 2 diabetes warrants further examination. ..
- Catalano M, Frairia R, Boccuzzi G, Fortunati N. Sex hormone-binding globulin antagonizes the anti-apoptotic effect of estradiol in breast cancer cells. Mol Cell Endocrinol. 2005;230:31-7 pubmed..Taken together, our observations suggest that the interaction of SHBG with MCF-7 cell membranes causes inhibition of the anti-apoptotic effect of estradiol which might account for SHBG's inhibitory effect on breast cancer cell growth. ..
- Panerai R, Dawson S, Eames P, Potter J. Cerebral blood flow velocity response to induced and spontaneous sudden changes in arterial blood pressure. Am J Physiol Heart Circ Physiol. 2001;280:H2162-74 pubmedThe influence of different types of maneuvers that can induce sudden changes of arterial blood pressure (ABP) on the cerebral blood flow velocity (CBFV) response was studied in 56 normal subjects (mean age 62 yr, range 23-80)...
- Vos M, Mijnhout G, Rondeel J, Baron W, Groeneveld P. Sex hormone binding globulin deficiency due to a homozygous missense mutation. J Clin Endocrinol Metab. 2014;99:E1798-802 pubmed publisherSHBG is known as the major sex steroid binding protein in plasma, and it regulates the bioavailability of both T and estradiol levels required for effects on target tissues...
- Detering M, Steels E, Koyyalamudi S, Allifranchini E, Bocchietto E, Vitetta L. Ageratum conyzoides L. inhibits 5-alpha-reductase gene expression in human prostate cells and reduces symptoms of benign prostatic hypertrophy in otherwise healthy men in a double blind randomized placebo controlled clinical study. Biofactors. 2017;: pubmed publisher..The secondary outcome measures were testosterone, dihydrotestosterone, oestradiol, sex hormone binding globulin (SHBG), Dehydroepiandrosterone sulfate (DHEA-S) and cortisol levels, and prostate specific antigen (PSA)..
- Lewis J, Jones L, Legge M, Elder P. Corticosteroid-binding globulin, cortisol, free cortisol, and sex hormone-binding globulin responses following oral glucose challenge in spinal cord-injured and able-bodied men. Horm Metab Res. 2010;42:882-6 pubmed publisher..There were no significant changes in plasma sex hormone-binding globulin in either group. ..
- Park S, Andreotti G, Sakoda L, Gao Y, Rashid A, Chen J, et al. Variants in hormone-related genes and the risk of biliary tract cancers and stones: a population-based study in China. Carcinogenesis. 2009;30:606-14 pubmed publisher..1-4.9; P-interaction = 0.05) was statistically significant. Our findings suggest that common variants in hormone-related genes contribute to the risk of biliary tract cancers and stones, possibly by modulating hormone metabolism. ..
- Verity K, Fuller P. Isolation of a rat amiloride-binding protein cDNA clone: tissue distribution and regulation of expression. Am J Physiol. 1994;266:C1505-12 pubmed..gene expression in sodium-transporting epithelia by corticosteroids, we have cloned an amiloride-binding protein (ABP) cDNA from rat descending colon and kidney...
- Raps M, Helmerhorst F, Fleischer K, Thomassen S, Rosendaal F, Rosing J, et al. Sex hormone-binding globulin as a marker for the thrombotic risk of hormonal contraceptives. J Thromb Haemost. 2012;10:992-7 pubmed publisher..SHBG levels were positively associated with both the nAPCsr and the risks of venous thrombosis reported in the recent literature. SHBG is a useful marker with which to estimate the thrombotic safety of a preparation. ..
- del Mar Grasa M, Villarreal L, Granero R, Vila R, Penelo E, Aguera Z, et al. Purging behavior modulates the relationships of hormonal and behavioral parameters in women with eating disorders. Neuropsychobiology. 2013;67:230-40 pubmed publisher..Correlations of selected psychometric data and the CBG/SHBG levels in purging may eventually result in clinical markers. This approach may provide additional clues for understanding the pathogenesis of ED. ..
- Pang X, Yuan Y, Sun Y, Shen J, Zha X, Hu Y. The relationship of sex hormone-binding globulin (SHBG) gene polymorphisms with serum SHBG level and metabolic syndrome in Chinese Han males. Aging Clin Exp Res. 2014;26:583-9 pubmed publisher..The risk of MetS rose with the decrease in serum SHBG levels for rs6259 and rs376021 carriers. rs6259 and rs3760213 SNPs are associated with the risk of MetS and lower serum SHBG level in Chinese Han males. ..
- Stoddard E, Killinger B, Nair R, Sadler N, Volk R, Purvine S, et al. Activity-Based Probes for Isoenzyme- and Site-Specific Functional Characterization of Glutathione S-Transferases. J Am Chem Soc. 2017;139:16032-16035 pubmed publisher..Therefore, we developed (1) a GSH-based photoaffinity probe (GSTABP-G) to target the "G site", and (2) an ABP designed to mimic a substrate molecule and have "H site" activity (GSTABP-H)...
- Perez C, Araneda C, Estay F, Díaz N, Vizziano Cantonnet D. Sex hormone-binding globulin b expression in the rainbow trout ovary prior to sex differentiation. Gen Comp Endocrinol. 2017;: pubmed publisher..These results suggest that Shbgb is involved in early ovarian differentiation, supporting an important role for the salmonid shbgb gene in sex determination...
- Awwad N, AlShahrani A, Saleh K, Hamdy M, Bahmani F, Asemi Z. Effect of Two Different Doses of Vitamin D Supplementation on Metabolic Profiles of Insulin-Resistant Patients with Polycystic Ovary Syndrome. Nutrients. 2017;9: pubmed publisher....
- Pence J, Clancy K, Harley B. Proangiogenic Activity of Endometrial Epithelial and Stromal Cells in Response to Estradiol in Gelatin Hydrogels. Adv Biosyst. 2017;1: pubmed publisher..Given the transience of hormonal signals within 3D biomaterials, the inclusion of sex hormone binding globulin (SHBG) to alter the bioavailability of estradiol within the hydrogel is reported, demonstrating a ..