Genomes and Genes
sex hormone binding globulin
Summary: A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as ANDROGEN-BINDING PROTEIN. They differ by their sites of synthesis and post-translational oligosaccharide modifications.
- Riancho J, Valero C, Zarrabeitia M, Garcia Unzueta M, Amado J, Gonzalez Macias J. Genetic polymorphisms are associated with serum levels of sex hormone binding globulin in postmenopausal women. BMC Med Genet. 2008;9:112 pubmed publisherEstrogen activity plays a critical role in bone homeostasis. The serum levels of sex hormone binding globulin (SHBG) influence free estrogen levels and activity on target tissues...
- Ahn J, Schumacher F, Berndt S, Pfeiffer R, Albanes D, Andriole G, et al. Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3). Hum Mol Genet. 2009;18:3749-57 pubmed publisher..8%, P = 1.82 x 10(-6)). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones. ..
- Akin F, Bastemir M, Alkis E, Kaptanoglu B. Associations between sex hormone binding globulin and metabolic syndrome parameters in premenopausal obese women. Indian J Med Sci. 2008;62:407-15 pubmedThe aim of this study was to determine sex hormone binding globulin (SHBG) concentrations in premenopausal obese women and to evaluate the relationships between sex hormones and features of the metabolic syndrome (MetS)...
- Caldwell J, Jirikowski G. Sex hormone binding globulin and aging. Horm Metab Res. 2009;41:173-82 pubmed publisher..This review will discuss the possibility that sex hormone binding globulin (SHBG) plays an active role in the aging process...
- Kupelian V, Hayes F, Link C, Rosen R, McKinlay J. Inverse association of testosterone and the metabolic syndrome in men is consistent across race and ethnic groups. J Clin Endocrinol Metab. 2008;93:3403-10 pubmed publisher..A robust, dose-response relationship between sex hormone levels and odds of the metabolic syndrome in men is consistent across racial/ethnic groups. ..
- Bjørnerem A, Emaus N, Berntsen G, Joakimsen R, Fønnebø V, Wilsgaard T, et al. Circulating sex steroids, sex hormone-binding globulin, and longitudinal changes in forearm bone mineral density in postmenopausal women and men: the Tromsø study. Calcif Tissue Int. 2007;81:65-72 pubmed..We therefore conclude that the relations between sex steroids and bone loss are weak and measurements of sex steroids are unlikely to assist in clinical decision making. ..
- Araujo A, Travison T, Leder B, McKinlay J. Correlations between serum testosterone, estradiol, and sex hormone-binding globulin and bone mineral density in a diverse sample of men. J Clin Endocrinol Metab. 2008;93:2135-41 pubmed publisher..These findings suggest that differences in hormone levels are not a major contributor to the observed differences in BMD between Black, Hispanic, and white men. ..
- Gnanasekar M, Suleman F, Ramaswamy K, Caldwell J. Identification of sex hormone binding globulin-interacting proteins in the brain using phage display screening. Int J Mol Med. 2009;24:421-6 pubmedThe present study reports the identification of human sex hormone binding globulin (SHBG)-interacting proteins in the brain using a phage display-based screening technology...
- Giton F, Urien S, Born C, Tichet J, Guéchot J, Callebert J, et al. Determination of bioavailable testosterone [non sex hormone binding globulin (SHBG)-bound testosterone] in a population of healthy French men: influence of androstenediol on testosterone binding to SHBG. Clin Chem. 2007;53:2160-8 pubmed..When using the optimized binding constants, taking age-related 5-diol values into consideration slightly improves prediction of cBT. ..
- Andersson A, Jensen T, Juul A, Petersen J, Jørgensen T, Skakkebaek N. Secular decline in male testosterone and sex hormone binding globulin serum levels in Danish population surveys. J Clin Endocrinol Metab. 2007;92:4696-705 pubmed..The observed age-independent changes in SHBG and testosterone may be explained by an initial change in SHBG levels, which subsequently lead to adjustment of testosterone at a lower level to sustain free testosterone levels. ..
- 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. ..
- Perry J, Weedon M, Langenberg C, Jackson A, Lyssenko V, SparsÃ¸ 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...
- Bjørnerem A, Ahmed L, Joakimsen R, Berntsen G, Fønnebø V, Jørgensen L, et al. A prospective study of sex steroids, sex hormone-binding globulin, and non-vertebral fractures in women and men: the Tromso Study. Eur J Endocrinol. 2007;157:119-25 pubmed..Sex steroids were not associated with fracture risk. Measurements of sex steroids or SHBG are unlikely to assist in decision making regarding fracture risk susceptibility. ..
- Caldwell J, Suleman F, Jirikowski G. Internalization of sex hormone binding globulin into fibroblast 3T3 cells. Horm Metab Res. 2007;39:620-2 pubmed
- Yasui T, Tomita J, Miyatani Y, Yamada M, Uemura H, Irahara M, et al. Associations of adiponectin with sex hormone-binding globulin levels in aging male and female populations. Clin Chim Acta. 2007;386:69-75 pubmed..Correlations between adiponectin and SHBG were significantly positive in both men and women, and both adiponectin and SHBG might be involved in insulin resistance in both sexes. ..
- Kapoor D, Clarke S, Channer K, Jones T. Erectile dysfunction is associated with low bioactive testosterone levels and visceral adiposity in men with type 2 diabetes. Int J Androl. 2007;30:500-7 pubmed..This study has shown that ED is associated with low bioavailable and free testosterone levels, age, visceral adiposity and hypertension in type 2 diabetic men. ..
- Hammond G, Hogeveen K, Visser M, Coelingh Bennink H. Estetrol does not bind sex hormone binding globulin or increase its production by human HepG2 cells. Climacteric. 2008;11 Suppl 1:41-6 pubmed publisherTo determine whether human sex hormone binding globulin (SHBG) binds estetrol (E4), and to assess whether E4 stimulates the production of SHBG by human hepatocytes...
- Leppänen V, Tossavainen H, Permi P, Lehtiö L, Rönnholm G, Goldman A, et al. Crystal structure of the N-terminal NC4 domain of collagen IX, a zinc binding member of the laminin-neurexin-sex hormone binding globulin (LNS) domain family. J Biol Chem. 2007;282:23219-30 pubmed..The structure is similar to previously characterized laminin-neurexin-sex hormone binding globulin (LNS) structures, dominated by an antiparallel beta-sheet sandwich...
- 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. ..
- Muller M, Schupf N, Manly J, Mayeux R, Luchsinger J. Sex hormone binding globulin and incident Alzheimer's disease in elderly men and women. Neurobiol Aging. 2010;31:1758-65 pubmed publisher..Whether SHBG is causally related to dementia or whether it is a surrogate marker for rate of biological aging and increased risk or for preclinical stage of dementia has to be elucidated. ..
- Hanna F, Bell R, Cicuttini F, Davison S, Wluka A, Davis S. The relationship between endogenous testosterone, preandrogens, and sex hormone binding globulin and knee joint structure in women at midlife. Semin Arthritis Rheum. 2007;37:56-62 pubmedTo evaluate the relationship between serum testosterone (T), preandrogens and sex hormone binding globulin (SHBG), and the knee structure in middle-aged women without knee pain...
- Spencer K, Yu C, Rembouskos G, Bindra R, Nicolaides K. First trimester sex hormone-binding globulin and subsequent development of preeclampsia or other adverse pregnancy outcomes. Hypertens Pregnancy. 2005;24:303-11 pubmed..Levels are reduced in those who subsequently miscarry or in those presenting with diabetes. ..
- Ng K, Catalano M, Pinós T, Selva D, Avvakumov G, Munell F, et al. Evidence that fibulin family members contribute to the steroid-dependent extravascular sequestration of sex hormone-binding globulin. J Biol Chem. 2006;281:15853-61 pubmed..Given the interplay between fibulins and numerous proteins within the basal lamina, interactions between SHBG and matrix proteins may exert novel biological effects. ..
- Selva D, Hammond G. Human sex hormone-binding globulin is expressed in testicular germ cells and not in sertoli cells. Horm Metab Res. 2006;38:230-5 pubmed..These remarkable differences in human SHBG expression in the testis, when compared to other mammals, force us to reconsider the functional significance of SHBG expression in the testis in relation to male reproduction. ..
- Osuna J, Gomez Perez R, Arata Bellabarba G, Villaroel V. Relationship between BMI, total testosterone, sex hormone-binding-globulin, leptin, insulin and insulin resistance in obese men. Arch Androl. 2006;52:355-61 pubmed..313; p < 0.01) and insulin resistance (= -0.266; p < 0.05). Our results shows that in a sample of men, Tt and SHBG concentrations proportionally diminished with both the increase of BMI and insulin resistance index. ..
- Warren R, Skinner J, Sala E, Denton E, Dowsett M, Folkerd E, et al. Associations among mammographic density, circulating sex hormones, and polymorphisms in sex hormone metabolism genes in postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2006;15:1502-8 pubmed
- Rosner W. Sex steroids and the free hormone hypothesis. Cell. 2006;124:455-6; author reply 456-7 pubmed
- Heald A, Anderson S, Ivison F, Riste L, Laing I, Cruickshank J, et al. Low sex hormone binding globulin is a potential marker for the metabolic syndrome in different ethnic groups. Exp Clin Endocrinol Diabetes. 2005;113:522-8 pubmed..As ethnic differences in SHBG level closely parallel differences in insulin resistance. Its measurement may be useful in identifying individuals at particular risk of the metabolic syndrome, for early intervention. ..
- Schobert R, Bernhardt G, Biersack B, Bollwein S, Fallahi M, Grotemeier A, et al. Steroid conjugates of dichloro(6-aminomethylnicotinate)platinum(II): effects on DNA, sex hormone binding globulin, the estrogen receptor, and various breast cancer cell lines. ChemMedChem. 2007;2:333-42 pubmed..Their affinities towards sex hormone binding globulin (SHBG) and towards the nuclear estrogen receptor ER(alpha) were assessed by competitive displacement ..
- 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. ..
- Khosla S. Editorial: Sex hormone binding globulin: inhibitor or facilitator (or both) of sex steroid action?. J Clin Endocrinol Metab. 2006;91:4764-6 pubmed
- 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. ..
- Rinaldi S, Key T, Peeters P, Lahmann P, Lukanova A, Dossus L, et al. Anthropometric measures, endogenous sex steroids and breast cancer risk in postmenopausal women: a study within the EPIC cohort. Int J Cancer. 2006;118:2832-9 pubmed..Our data indicate that the relationship of adiposity with breast cancer in postmenopausal women could be partially explained by the increases in endogenous estrogens, and by a decrease in levels of SHBG. ..
- Gapstur S, Kopp P, Gann P, Chiu B, Colangelo L, Liu K. Changes in BMI modulate age-associated changes in sex hormone binding globulin and total testosterone, but not bioavailable testosterone in young adult men: the CARDIA Male Hormone Study. Int J Obes (Lond). 2007;31:685-91 pubmedTo compare age-associated 8-year changes in total testosterone, calculated bioavailable testosterone and sex hormone binding globulin (SHBG) across five groups of men stratified according to change in body mass index (BMI) (i.e...
- Greendale G, Palla S, Ursin G, Laughlin G, Crandall C, Pike M, et al. The association of endogenous sex steroids and sex steroid binding proteins with mammographic density: results from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study. Am J Epidemiol. 2005;162:826-34 pubmed..These results suggest that some sex steroids may increase the risk of breast cancer by stimulating breast epithelial or stromal proliferation, which appears on a mammogram as higher density. ..
- Kapoor D, Aldred H, Clark S, Channer K, Jones T. Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes: correlations with bioavailable testosterone and visceral adiposity. Diabetes Care. 2007;30:911-7 pubmed..Testosterone levels are frequently low in men with type 2 diabetes, and the majority of these men have symptoms of hypogonadism. Obesity is associated with low testosterone levels in diabetic men. ..
- 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. ..
- 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...
- Selva D, Bassas L, Munell F, Mata A, Tekpetey F, Lewis J, et al. Human sperm sex hormone-binding globulin isoform: characterization and measurement by time-resolved fluorescence immunoassay. J Clin Endocrinol Metab. 2005;90:6275-82 pubmed..Sperm SHBG isoform levels correlate significantly with age and sperm motility and may influence sperm function in relation to male fertility. ..
- 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. ..
- Eliassen A, Missmer S, Tworoger S, Spiegelman D, Barbieri R, Dowsett M, et al. Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. J Natl Cancer Inst. 2006;98:1406-15 pubmed..Levels of circulating estrogens and androgens may be important in the etiology of premenopausal breast cancer. ..
- Selvin E, Feinleib M, Zhang L, Rohrmann S, Rifai N, Nelson W, et al. Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care. 2007;30:234-8 pubmed..27). Low free and bioavailable testosterone concentrations in the normal range were associated with diabetes, independent of adiposity. These data suggest that low androgen levels may be a risk factor for diabetes 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. ..
- Nielsen T, Hagen C, Wraae K, Brixen K, Petersen P, Haug E, et al. Visceral and subcutaneous adipose tissue assessed by magnetic resonance imaging in relation to circulating androgens, sex hormone-binding globulin, and luteinizing hormone in young men. J Clin Endocrinol Metab. 2007;92:2696-705 pubmed..The reference intervals for total testosterone, bioavailable testosterone, free testosterone, and DHT are displaced toward lower limits in obese men. ..
- Caldwell J, Suleman F, Chou S, Shapiro R, Herbert Z, Jirikowski G. Emerging roles of steroid-binding globulins. Horm Metab Res. 2006;38:206-18 pubmed
- 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. ..
- 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. ..
- Kapoor D, Malkin C, Channer K, Jones T. Androgens, insulin resistance and vascular disease in men. Clin Endocrinol (Oxf). 2005;63:239-50 pubmed
- Sørensen K, Andersson A, Skakkebaek N, Juul A. Serum sex hormone-binding globulin levels in healthy children and girls with precocious puberty before and during gonadotropin-releasing hormone agonist treatment. J Clin Endocrinol Metab. 2007;92:3189-96 pubmed..Studies on insulin sensitivity and SHBG in puberty are needed to better understand the interaction between body composition and gonadal maturation. ..
- Shifren J, Rifai N, Desindes S, McIlwain M, Doros G, Mazer N. A comparison of the short-term effects of oral conjugated equine estrogens versus transdermal estradiol on C-reactive protein, other serum markers of inflammation, and other hepatic proteins in naturally menopausal women. J Clin Endocrinol Metab. 2008;93:1702-10 pubmed publisher..Compared with oral CEE, transdermal E2 exerts minimal effects on CRP and the other inflammation and hepatic parameters. ..
- Meeker J, Rossano M, Protas B, Padmanahban V, Diamond M, Puscheck E, et al. Environmental exposure to metals and male reproductive hormones: circulating testosterone is inversely associated with blood molybdenum. Fertil Steril. 2010;93:130-40 pubmed publisher..Although reductions in T and reproductive toxicity after molybdenum exposure have been previously demonstrated in animal studies, more research is needed to determine whether molybdenum poses a risk to human reproductive health. ..
- Mölleken D, Richter Appelt H, Stodieck S, Bengner T. Sexual quality of life in epilepsy: correlations with sex hormone blood levels. Epilepsy Behav. 2009;14:226-31 pubmed publisher..Avoiding enzyme-inducing antiepileptic drugs may lower the risk of raised sex hormone-binding globulin levels and, thus, of lowered sexual quality of life in men with epilepsy. ..
- Villeneuve M, Ostlund R, Baillargeon J. Hyperinsulinemia is closely related to low urinary clearance of D-chiro-inositol in men with a wide range of insulin sensitivity. Metabolism. 2009;58:62-8 pubmed publisher..The apparent discrepancy with PCOS women might be explained by higher insulin levels in men as compared with women and requires confirmation. ..