Sex hormone-binding globulin

Testosterone and estradiol circulate in the bloodstream, loosely bound mostly to serum albumin (~54%), and to a lesser extent bound tightly to SHBG (~44%). Only a very small fraction of about 1 to 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, the local bioavailability of sex hormones is influenced by the level of SHBG. Because SHBG binds to testosterone (T) and dihydrotestosterone (DHT), these hormones are made less lipophilic and become concentrated within the luminal fluid of the seminiferous tubules. The higher levels of these hormones enable spermatogenesis in the seminiferous tubules and sperm maturation in the epididymis. SHBG’s production is regulated under the influence of FSH{{cite journal | vauthors = Hansson V, Weddington SC, French FS, McLean W, Smith A, Nayfeh SN, Ritzén EM, Hagenäs L | title = Secretion and role of androgen-binding proteins in the testis and epididymis | journal = Journal of Reproduction and Fertility. Supplement | issue = 24 suppl | pages = 17–33 | date = September 1976 | pmid = 1069850 }} on Sertoli cells, enhanced by insulin, retinol, and testosterone.

The relative binding affinity of various sex steroids for SHBG is dihydrotestosterone (DHT) > testosterone > androstenediol > estradiol > estrone.{{cite journal | vauthors = Somboonporn W, Davis SR | title = Testosterone effects on the breast: implications for testosterone therapy for women | journal = Endocrine Reviews | volume = 25 | issue = 3 | pages = 374–88 | date = June 2004 | pmid = 15180949 | doi = 10.1210/er.2003-0016 | doi-access = free }} DHT binds to SHBG with about 5 times the affinity of testosterone and about 20 times the affinity of estradiol. Dehydroepiandrosterone (DHEA) is weakly bound to SHBG, but dehydroepiandrosterone sulfate is not bound to SHBG. Androstenedione is not bound to SHBG either, and is instead bound solely to albumin.{{cite book | vauthors = Becker K, Bilezikian JP, Bremner WJ, Hung W, Kahn CR | title = Principles and Practice of Endocrinology and Metabolism | url = https://books.google.com/books?id=FVfzRvaucq8C | access-date = 4 August 2012 | date = 24 April 2001 | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-1750-2}} Estrone sulfate and estriol are also poorly bound by SHBG.{{cite book | vauthors = Quirk Jr G, Wendel Jr GD| chapter = Biologic Effects of Natural and Synthetic Estrogens | veditors = Buchsbaum HJ | title = The Menopause| chapter-url=https://books.google.com/books?id=z0LuBwAAQBAJ&pg=PA62|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-5525-3|pages=62–}} Less than 1% of progesterone is bound to SHBG.{{cite book | vauthors = Fritz MA, Speroff L |title=Clinical Gynecologic Endocrinology and Infertility|url=https://books.google.com/books?id=KZLubBxJEwEC&pg=PA44|date=28 March 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-4847-3|pages=44–}}

SHBG levels are usually about twice as high in women as in men. In women, SHBG serves to limit exposure to both androgens and estrogens. Low SHBG levels in women have been associated with hyperandrogenism and endometrial cancer due to heightened exposure to androgens and estrogens, respectively. During pregnancy, due to activation of SHBG production in the liver by high estrogen levels, SHBG levels increase by five-fold to ten-fold. The high SHBG levels during pregnancy may serve to protect the mother from exposure to fetal androgens that escape metabolism by the placenta. A case report of severe hyperandrogenism in a pregnant woman due to a rare instance of genetic SHBG deficiency illustrates this.{{cite journal | vauthors = Hogeveen KN, Cousin P, Pugeat M, Dewailly D, Soudan B, Hammond GL | title = Human sex hormone-binding globulin variants associated with hyperandrogenism and ovarian dysfunction | journal = J. Clin. Invest. | volume = 109 | issue = 7 | pages = 973–81 | date = April 2002 | pmid = 11927624 | pmc = 150924 | doi = 10.1172/JCI14060 }}

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 called Shbg, located on chromosome 17 on the short arm between the bands 17p12→p13.* {{cite journal | vauthors = Bérubé D, Séralini GE, Gagné R, Hammond GL | title = Localization of the human sex hormone-binding globulin gene (SHBG) to the short arm of chromosome 17 (17p12----p13) | journal = Cytogenetics and Cell Genetics | volume = 54 | issue = 1–2 | pages = 65–7 | year = 1991 | pmid = 2249477 | doi = 10.1159/000132958 }} Overlapping on the complementary DNA strand is the gene for spermidine/spermine N1-acetyltransferase family member 2 (SAT2). Nearby are the genes for p53 and ATP1B2, and fragile X mental retardation, autosomal homolog 2 (FXR2) on the complementary strand.{{cite journal | vauthors = Joseph DR | title = The rat androgen-binding protein (ABP/SHBG) gene contains triplet repeats similar to unstable triplets: evidence that the ABP/SHBG and the fragile X-related 2 genes overlap | journal = Steroids | volume = 63 | issue = 1 | pages = 2–4 | date = January 1998 | pmid = 9437788 | doi = 10.1016/S0039-128X(97)00087-1 | s2cid = 12825993 }} There are eight exons, of which exon 1 has three variations called 1L, 1T and 1N which are triggered by three promoters: P_L, P_T and P_N respectively. SHBG comes with the 1L, 2, 3, 4, 5, 6, 7, and 8 exons connected together. A variation includes SHBG-T which is missing exon 7 but with exon 1T promoted by promoter P_T on the opposite strand, which shared with that for SAT2.{{cite journal | vauthors = Nakhla AM, Hryb DJ, Rosner W, Romas NA, Xiang Z, Kahn SM | title = Human sex hormone-binding globulin gene expression- multiple promoters and complex alternative splicing | journal = BMC Molecular Biology | volume = 10 | issue = 1 | pages = 37 | date = May 2009 | pmid = 19416531 | pmc = 2694190 | doi = 10.1186/1471-2199-10-37 | doi-access = free }}

There are variations in the genetic material for this protein that have different effects.

In humans common polymorphisms include the following:

Rs6259, also called Asp327Asn location 7633209 on chromosome 17, results in there being an extra N-glycosylation site, and so an extra sugar can be attached. This results in a longer circulation half-life for the protein, and raised levels. Health effects include a lowered risk of endometrial cancer and an increased risk of systemic lupus erythematosus.{{cite journal | vauthors = Piotrowski P, Gasik R, Lianeri M, Cieślak D, Wudarski M, Hrycaj P, Łacki JK, Jagodziński PP | title = Asp327Asn polymorphism of sex hormone-binding globulin gene is associated with systemic lupus erythematosus incidence | journal = Molecular Biology Reports | volume = 37 | issue = 1 | pages = 235–9 | date = January 2010 | pmid = 19649728 | doi = 10.1007/s11033-009-9639-7 | s2cid = 38541900 }}

Rs6258 also called Ser156Pro is at position 7631360 on chromosome 17.

Rs727428 position 7634474 is in several percent of humans.{{cite journal | vauthors = Svartberg J, Schirmer H, Wilsgaard T, Mathiesen EB, Njølstad I, Løchen ML, Jorde R | title = Single-nucleotide polymorphism, rs1799941 in the Sex Hormone-Binding Globulin (SHBG) gene, related to both serum testosterone and SHBG levels and the risk of myocardial infarction, type 2 diabetes, cancer and mortality in men: the Tromsø Study | journal = Andrology | volume = 2 | issue = 2 | pages = 212–8 | date = March 2014 | pmid = 24327369 | doi = 10.1111/j.2047-2927.2013.00174.x | s2cid = 206007163 | doi-access = free }}

(TAAAA)(n) is five base pairs that repeats a variable number of times on the opposite DNA strand.{{cite journal | vauthors = Thompson DJ, Healey CS, Baynes C, Kalmyrzaev B, Ahmed S, Dowsett M, Folkerd E, Luben RN, Cox D, Ballinger D, Pharoah PD, Ponder BA, Dunning AM, Easton DF | title = Identification of common variants in the SHBG gene affecting sex hormone-binding globulin levels and breast cancer risk in postmenopausal women | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 17 | issue = 12 | pages = 3490–8 | date = December 2008 | pmid = 19064566 | pmc = 2660245 | doi = 10.1158/1055-9965.EPI-08-0734 }}

The mechanism of activating the promoter for SHBG in the liver involves hepatocyte nuclear factor 4 alpha (HNF4A) binding to a DR1-like cis-element which then stimulates production. Competing with HNF4A at a third site on the promoter is PPARG-2 which reduces copying the gene to RNA. If the HNF4A level is low, then COUP-TF binds to the first site and turns off production of SHBG.

Sex hormone-binding globulin is homodimeric, meaning it has two identical peptide chains making up its structure. The amino acid sequence is the same as for androgen-binding protein produced in testes, but with different oligosaccharides attached.{{cite journal | vauthors = Hammond GL, Bocchinfuso WP | title = Sex hormone-binding globulin: gene organization and structure/function analyses | journal = Hormone Research | volume = 45 | issue = 3–5 | pages = 197–201 | year = 1996 | pmid = 8964583 | doi = 10.1159/000184787 }}

SHBG has two laminin G-like domains which form pockets that bind hydrophobic molecules. The steroids are bound by the LG domain at the amino end of the protein. Inside the pocket of the domain is a serine residue that attracts the two different types of steroids at different points, thus changing their orientation. Androgens bind at the C3 functional groups on the A ring, and estrogens bind via a hydroxyl attached to C17 on the D ring. The two different orientations change a loop over the entrance to the pocket and the position of trp84 (in humans). Thus the whole protein signals what hormone it carries on its own surface. The steroid binding LG domain is coded by exons 2 to 5. A linker region joins the two LG domains together.

When first produced, the SHBG precursor has a leading signal peptide attached with 29 amino acids. The remaining peptide has 373 amino acids. There are two sulfur bridges.

The sugars are attached at two different N-glycosylation points on asparagine (351 and 367) and one O-glycosylation point (7) on threonine.{{cite journal | vauthors = Hammond GL, Underhill DA, Smith CL, Goping IS, Harley MJ, Musto NA, Cheng CY, Bardin CW | title = The cDNA-deduced primary structure of human sex hormone-binding globulin and location of its steroid-binding domain | journal = FEBS Letters | volume = 215 | issue = 1 | pages = 100–4 | date = May 1987 | pmid = 3569533 | doi = 10.1016/0014-5793(87)80121-7 | bibcode = 1987FEBSL.215..100H | s2cid = 23058156 }}

A calcium ion is needed to link the two elements of the dimer together. Also a zinc ion is used to orient an otherwise disorganised part of the peptide chain.

SHBG has both enhancing and inhibiting hormonal influences and thus can be viewed as a hepatokine. It decreases with high levels of insulin, growth hormone, insulin-like growth factor 1 (IGF-1), androgens, prolactin and transcortin. High estrogen and thyroxine levels 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 interleukins reduce SHBG, whereas insulin does not. For 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,{{cite journal | vauthors = Selva DM, Hammond GL | title = Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4alpha | journal = Journal of Molecular Endocrinology | volume = 43 | issue = 1 | pages = 19–27 | date = July 2009 | pmid = 19336534 | doi = 10.1677/JME-09-0025 | doi-access = free }} was downregulation of hepatocyte nuclear factor 4 (HNF4).{{cite journal | vauthors = Selva DM, Hogeveen KN, Innis SM, Hammond GL | title = Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene | journal = The Journal of Clinical Investigation | volume = 117 | issue = 12 | pages = 3979–87 | date = December 2007 | pmid = 17992261 | pmc = 2066187 | doi = 10.1172/JCI32249}}

• {{cite web |date=November 10, 2007 |title=Too much sugar turns off gene that controls the effects of sex steroids |website=Medical Xpress |url=https://medicalxpress.com/news/2007-11-sugar-gene-effects-sex-steroids.html}}{{cite journal | vauthors = Simó R, Barbosa-Desongles A, Hernandez C, Selva DM | title = IL1β down-regulation of sex hormone-binding globulin production by decreasing HNF-4α via MEK-1/2 and JNK MAPK pathways | journal = Molecular Endocrinology | volume = 26 | issue = 11 | pages = 1917–27 | date = November 2012 | pmid = 22902540 | pmc = 5416961 | doi = 10.1210/me.2012-1152 }}{{cite journal | vauthors = Simó R, Barbosa-Desongles A, Lecube A, Hernandez C, Selva DM | title = Potential role of tumor necrosis factor-α in downregulating sex hormone-binding globulin | journal = Diabetes | volume = 61 | issue = 2 | pages = 372–82 | date = February 2012 | pmid = 22210320 | pmc = 3266423 | doi = 10.2337/db11-0727 }}{{cite journal | vauthors = Goto A, Morita A, Goto M, Sasaki S, Miyachi M, Aiba N, Terauchi Y, Noda M, Watanabe S | title = Associations of sex hormone-binding globulin and testosterone with diabetes among men and women (the Saku Diabetes study): a case control study | journal = Cardiovascular Diabetology | volume = 11 | pages = 130 | date = October 2012 | pmid = 23066943 | pmc = 3537568 | doi = 10.1186/1475-2840-11-130 | doi-access = free }}

Reference ranges for blood tests for SHBG have been developed:[http://www.mayomedicallaboratories.com/test-catalog/print.php?unit_code=91215 Unit Code 91215] {{webarchive|url=https://web.archive.org/web/20110720111631/http://www.mayomedicallaboratories.com/test-catalog/print.php?unit_code=91215 |date=2011-07-20 }} at Mayo Clinic Medical Laboratories. Retrieved April 2011[https://androgenhacker.com/lower-shbg#shbg-levels-by-age-chart]{{cite web | vauthors = Becker DM |date=2019-07-27 |title=10 Simple Ways To Lower SHBG (#9 Is Fake News!) |url=https://androgenhacker.com/lower-shbg#shbg-levels-by-age-chart}}

File:Estrogen, progesterone, testosterone, and SHBG levels during pregnancy in women.png

File:Sex hormone-binding globulin (SHBG) and estradiol levels during pregnancy in women.png

File:Sex hormone-binding globulin binding capacity during pregnancy in women.png

SHBG levels are decreased by androgens, administration of anabolic steroids,{{cite journal | vauthors = Ruokonen A, Alén M, Bolton N, Vihko R | title = Response of serum testosterone and its precursor steroids, SHBG and CBG to anabolic steroid and testosterone self-administration in man | journal = Journal of Steroid Biochemistry | volume = 23 | issue = 1 | pages = 33–8 | date = July 1985 | pmid = 3160892 | doi = 10.1016/0022-4731(85)90257-2 }} polycystic ovary syndrome (PCOS), hypothyroidism, obesity, Cushing's syndrome, and acromegaly. Low SHBG levels increase the probability of type 2 diabetes.{{cite journal | vauthors = Ding EL, Song Y, Manson JE, Hunter DJ, Lee CC, Rifai N, Buring JE, Gaziano JM, Liu S | title = Sex hormone-binding globulin and risk of type 2 diabetes in women and men | journal = The New England Journal of Medicine | volume = 361 | issue = 12 | pages = 1152–63 | date = September 2009 | pmid = 19657112 | pmc = 2774225 | doi = 10.1056/NEJMoa0804381 }} SHBG levels increase with estrogenic states (oral contraceptives), pregnancy, hyperthyroidism, cirrhosis, anorexia nervosa, and certain drugs. Long-term calorie restriction increases SHBG in rodents and men, while lowering free and total testosterone and estradiol and having no effect on DHEA-S, which lacks affinity for SHBG.{{cite journal | vauthors = Cangemi R, Friedmann AJ, Holloszy JO, Fontana L | title = Long-term effects of calorie restriction on serum sex-hormone concentrations in men | journal = Aging Cell | volume = 9 | issue = 2 | pages = 236–42 | date = April 2010 | pmid = 20096034 | pmc = 3569090 | doi = 10.1111/j.1474-9726.2010.00553.x }} PCOS is associated with insulin resistance and excess insulin lowers SHBG, which increases free testosterone levels.{{cite journal | vauthors = Manni A, Pardridge WM, Cefalu W, Nisula BC, Bardin CW, Santner SJ, Santen RJ | title = Bioavailability of albumin-bound testosterone | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 61 | issue = 4 | pages = 705–10 | date = October 1985 | pmid = 4040924 | doi = 10.1210/jcem-61-4-705 }}

In utero, the human fetus has a low level of SHBG, allowing increased activity of sex hormones. After birth, the SHBG level rises and remains at a high level throughout childhood. At puberty the SHBG level halves in girls and goes down to a quarter in boys. The change at puberty is triggered by growth hormone, and its pulsatility differs in boys and girls.{{Clarify|reason=|date=September 2019}} In the third trimester of pregnancy, the SHBG level of the parent escalates to five to ten times the usual level for a woman. A hypothesis is that this protects against the effect of hormone produced by the fetus.

Obese girls are more likely to have an early menarche due to lower levels of SHBG. Anorexia or a lean physique in women leads to higher SHBG levels, which in turn can lead to amenorrhea.

Reduced levels of SHBG and also certain polymorphisms of the SHBG gene are implicated in the development of insulin resistance and type 2 diabetes.{{cite journal | vauthors = Le TN, Nestler JE, Strauss JF, Wickham EP | title = Sex hormone-binding globulin and type 2 diabetes mellitus | journal = Trends in Endocrinology and Metabolism | volume = 23 | issue = 1 | pages = 32–40 | date = January 2012 | pmid = 22047952 | doi = 10.1016/j.tem.2011.09.005 | pmc = 3351377 }} Such effects apparently involve direct action at the cellular level where it became apparent that cell membranes of certain tissues contain specific high-affinity SHBG receptors.{{cite journal | vauthors = Rosner W, Hryb DJ, Kahn SM, Nakhla AM, Romas NA | title = Interactions of sex hormone-binding globulin with target cells | journal = Molecular and Cellular Endocrinology | volume = 316 | issue = 1 | pages = 79–85 | date = March 2010 | pmid = 19698759 | doi = 10.1016/j.mce.2009.08.009 | s2cid = 27912941 }}

SHBG is a useful correlate and indirect marker of estrogen-induced procoagulation and by extension thrombosis, for instance with birth control pills.{{cite journal | vauthors = Tchaikovski SN, Rosing J | title = Mechanisms of estrogen-induced venous thromboembolism | journal = Thromb Res | volume = 126 | issue = 1 | pages = 5–11 | date = July 2010 | pmid = 20163835 | doi = 10.1016/j.thromres.2010.01.045 | url = }}{{cite journal | vauthors = Odlind V, Milsom I, Persson I, Victor A | title = Can changes in sex hormone binding globulin predict the risk of venous thromboembolism with combined oral contraceptive pills? | journal = Acta Obstet Gynecol Scand | volume = 81 | issue = 6 | pages = 482–90 | date = June 2002 | pmid = 12047300 | doi = | url = }}{{cite journal | vauthors = Morimont L, Haguet H, Dogné JM, Gaspard U, Douxfils J | title = Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk | journal = Front Endocrinol (Lausanne) | volume = 12 | issue = | pages = 769187 | date = 2021 | pmid = 34956081 | pmc = 8697849 | doi = 10.3389/fendo.2021.769187 | url = | doi-access = free }}

Oral contraceptives containing ethinylestradiol can increase SHBG levels 2- to 4-fold and decrease free testosterone concentrations by 40 to 80% in women.{{cite book|author1=IARC Working Group on the Evaluation of Carcinogenic Risks to Humans|author2=World Health Organization|author3=International Agency for Research on Cancer|title=Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy|url=https://books.google.com/books?id=aGDU5xibtNgC&pg=PA157|year=2007|publisher=World Health Organization|isbn=978-92-832-1291-1|page = 157 }} They can be used to treat symptoms of hyperandrogenism like acne and hirsutism. Some oral contraceptives, namely those containing high doses of ethinylestradiol (which have been discontinued and are no longer marketed), can increase SHBG levels as much as 5- to 10-fold.{{cite book| vauthors = Hammond GL |chapter=Sex Hormone-Binding Globulin and the Metabolic Syndrome|date = 25 April 2017|pages=305–324|doi=10.1007/978-3-319-53298-1_15| veditors = Winters SJ, Huhtaniemi IT | title = Male Hypogonadism: Basic, Clinical and Therapeutic Principles|publisher = Humana Press | isbn = 978-3-319-53298-1}}

Some medications, such as certain anabolic steroids like mesterolone and danazol and certain progestins like levonorgestrel and norethisterone, have high affinity for SHBG and can bind to it and displace endogenous steroids from it, thereby increasing free concentrations of these endogenous steroids.{{cite journal | vauthors = Pugeat MM, Dunn JF, Nisula BC | title = Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma | journal = J. Clin. Endocrinol. Metab. | volume = 53 | issue = 1 | pages = 69–75 | date = July 1981 | pmid = 7195405 | doi = 10.1210/jcem-53-1-69 }}{{cite journal | vauthors = Saartok T, Dahlberg E, Gustafsson JA | title = Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin | journal = Endocrinology | volume = 114 | issue = 6 | pages = 2100–6 | year = 1984 | pmid = 6539197 | doi = 10.1210/endo-114-6-2100 }}{{cite journal | vauthors = Kuhl H | title = Pharmacology of estrogens and progestogens: influence of different routes of administration | journal = Climacteric | volume = 8 | issue = Suppl 1 | pages = 3–63 | year = 2005 | pmid = 16112947 | doi = 10.1080/13697130500148875 | s2cid = 24616324 | url = http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf}} It has been estimated that therapeutic levels of danazol, methyltestosterone, fluoxymesterone, levonorgestrel, and norethisterone would respectively occupy or displace from testosterone 83–97%, 48–69%, 42–64%, 16–47%, and 4–39% of SHBG binding sites, while others with low affinity for SHBG such as ethinylestradiol, cyproterone acetate, and medroxyprogesterone acetate would occupy or displace from testosterone 1% or fewer SHBG binding sites.{{cite journal | vauthors = Pugeat MM, Dunn JF, Rodbard D, Nisula BC | title = The significance of drug interactions with human TeBG and CBG under physiological conditions: a new approach | journal = J. Steroid Biochem. | volume = 15 | pages = 487–90 | date = December 1981 | pmid = 7200170 | doi = 10.1016/0022-4731(81)90319-8 }}

Selective androgen receptor modulators (SARMs) also reduce SHBG.{{cite journal | vauthors = Machek SB, Cardaci TD, Wilburn DT, Willoughby DS | title = Considerations, possible contraindications, and potential mechanisms for deleterious effect in recreational and athletic use of selective androgen receptor modulators (SARMs) in lieu of anabolic androgenic steroids: A narrative review | journal = Steroids | volume = 164 | pages = 108753 | date = December 2020 | pmid = 33148520 | doi = 10.1016/j.steroids.2020.108753 | s2cid = 225049089 }}

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. Sex hormone-binding globulin can be measured separately from the total fraction of testosterone.

A free androgen index expresses the ratio of testosterone to SHBG and can be used to summarize the activity of free testosterone.

SHBG has been known under a variety of different names including:{{cite web | url = https://www.genecards.org/cgi-bin/carddisp.pl?gene=SHBG | title = SHBG | work = GeneCards }}{{cite book | chapter = Sex Steroid-Binding Protein | title = Steroid-Protein Interactions II | chapter-url = https://books.google.com/books?id=3DD6CAAAQBAJ&pg=PA198 | date = 6 December 2012 | publisher = Springer Science & Business Media | isbn = 978-3-642-82486-9 | page = 198 }}{{cite book | veditors = Litwack G, Westphal U | chapter = Structure, Function, and Regulation of Androgen-Binding Protein?Sex Hormone-Binding Globulin | title = Vitamins and Hormones: Steroids | chapter-url = https://books.google.com/books?id=ZBUjEoJu1MIC&pg=PA200|date=12 December 1994|publisher=Academic Press|isbn=978-0-08-086646-8 | pages = 200 }}

• Sex hormone-binding globulin (SHBG)
• Sex steroid-binding globulin (SSBG, SBG)
• Sex steroid-binding protein (SBP, SSBP)
• Androgen-binding protein (ABP)
• Estradiol-binding-protein (EBP)
• Testosterone–estradiol binding globulin (TeBG, TEBG)

{{Reflist|33em}}

{{refbegin|33em}}

• {{cite journal | vauthors = Rosner W, Hryb DJ, Khan MS, Nakhla AM, Romas NA | title = Sex hormone-binding globulin mediates steroid hormone signal transduction at the plasma membrane | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 69 | issue = 1–6 | pages = 481–5 | year = 1999 | pmid = 10419028 | doi = 10.1016/S0960-0760(99)00070-9 | s2cid = 6499033 }}
• {{cite journal | vauthors = Power SG, Bocchinfuso WP, Pallesen M, Warmels-Rodenhiser S, Van Baelen H, Hammond GL | title = Molecular analyses of a human sex hormone-binding globulin variant: evidence for an additional carbohydrate chain | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 75 | issue = 4 | pages = 1066–70 | date = October 1992 | pmid = 1400872 | doi = 10.1210/jcem.75.4.1400872 }}
• {{cite journal | vauthors = Gershagen S, Lundwall A, Fernlund P | title = Characterization of the human sex hormone binding globulin (SHBG) gene and demonstration of two transcripts in both liver and testis | journal = Nucleic Acids Research | volume = 17 | issue = 22 | pages = 9245–58 | date = November 1989 | pmid = 2587256 | pmc = 335128 | doi = 10.1093/nar/17.22.9245 }}
• {{cite journal | vauthors = Hammond GL, Underhill DA, Rykse HM, Smith CL | title = The human sex hormone-binding globulin gene contains exons for androgen-binding protein and two other testicular messenger RNAs | journal = Molecular Endocrinology | volume = 3 | issue = 11 | pages = 1869–76 | date = November 1989 | pmid = 2608061 | doi = 10.1210/mend-3-11-1869 | doi-access = free }}
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• {{cite journal | vauthors = Gershagen S, Fernlund P, Lundwall A | title = A cDNA coding for human sex hormone binding globulin. Homology to vitamin K-dependent protein S | journal = FEBS Letters | volume = 220 | issue = 1 | pages = 129–35 | date = August 1987 | pmid = 2956126 | doi = 10.1016/0014-5793(87)80890-6 | bibcode = 1987FEBSL.220..129G | s2cid = 13166151 }}
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• {{cite journal | vauthors = Hammond GL, Robinson PA, Sugino H, Ward DN, Finne J | title = Physicochemical characteristics of human sex hormone binding globulin: evidence for two identical subunits | journal = Journal of Steroid Biochemistry | volume = 24 | issue = 4 | pages = 815–24 | date = April 1986 | pmid = 3702459 | doi = 10.1016/0022-4731(86)90442-5 }}
• {{cite journal | vauthors = Hardy DO, Cariño C, Catterall JF, Larrea F | title = Molecular characterization of a genetic variant of the steroid hormone-binding globulin gene in heterozygous subjects | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 80 | issue = 4 | pages = 1253–6 | date = April 1995 | doi = 10.1210/jcem.80.4.7714097 | pmid = 7714097 }}
• {{cite journal | vauthors = Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES | title = Characterization of single-nucleotide polymorphisms in coding regions of human genes | journal = Nature Genetics | volume = 22 | issue = 3 | pages = 231–8 | date = July 1999 | pmid = 10391209 | doi = 10.1038/10290 | s2cid = 195213008 }}
• {{cite journal | vauthors = Grishkovskaya I, Avvakumov GV, Sklenar G, Dales D, Hammond GL, Muller YA | title = Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain | journal = The EMBO Journal | volume = 19 | issue = 4 | pages = 504–12 | date = February 2000 | pmid = 10675319 | pmc = 305588 | doi = 10.1093/emboj/19.4.504 }}
• {{cite journal | vauthors = Hogeveen KN, Talikka M, Hammond GL | title = Human sex hormone-binding globulin promoter activity is influenced by a (TAAAA)n repeat element within an Alu sequence | journal = The Journal of Biological Chemistry | volume = 276 | issue = 39 | pages = 36383–90 | date = September 2001 | pmid = 11473114 | doi = 10.1074/jbc.M104681200 | doi-access = free }}
• {{cite journal | vauthors = Hryb DJ, Nakhla AM, Kahn SM, St George J, Levy NC, Romas NA, Rosner W | title = Sex hormone-binding globulin in the human prostate is locally synthesized and may act as an autocrine/paracrine effector | journal = The Journal of Biological Chemistry | volume = 277 | issue = 29 | pages = 26618–22 | date = July 2002 | pmid = 12015315 | doi = 10.1074/jbc.M202495200 | doi-access = free }}
• {{cite journal | vauthors = Raineri M, Catalano MG, Hammond GL, Avvakumov GV, Frairia R, Fortunati N | title = O-Glycosylation of human sex hormone-binding globulin is essential for inhibition of estradiol-induced MCF-7 breast cancer cell proliferation | journal = Molecular and Cellular Endocrinology | volume = 189 | issue = 1–2 | pages = 135–43 | date = March 2002 | pmid = 12039072 | doi = 10.1016/S0303-7207(01)00725-0 | s2cid = 24123789 }}
• {{cite journal | vauthors = Grishkovskaya I, Avvakumov GV, Hammond GL, Muller YA | title = Resolution of a disordered region at the entrance of the human sex hormone-binding globulin steroid-binding site | journal = Journal of Molecular Biology | volume = 318 | issue = 3 | pages = 621–6 | date = May 2002 | pmid = 12054810 | doi = 10.1016/S0022-2836(02)00169-9 }}
• {{cite journal | vauthors = Thompson DJ, Healey CS, Baynes C, Kalmyrzaev B, Ahmed S, Dowsett M, Folkerd E, Luben RN, Cox D, Ballinger D, Pharoah PD, Ponder BA, Dunning AM, Easton DF | title = Identification of common variants in the SHBG gene affecting sex hormone-binding globulin levels and breast cancer risk in postmenopausal women | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 17 | issue = 12 | pages = 3490–8 | date = December 2008 | pmid = 19064566 | pmc = 2660245 | doi = 10.1158/1055-9965.EPI-08-0734 }}
• {{cite web|url=http://www.snpedia.com/index.php/SHBG|title=SHBG - SNPedia|last=Trkiehl|year=2011|access-date=13 July 2014}}

{{refend}}

• {{PDBe-KB2|P04278|Sex hormone-binding globulin}}
• {{MeshName|Androgen-Binding+Protein}}
• {{Ensembl|ENSG00000129214}}

{{PDB Gallery|geneid=6462}}

{{Carrier proteins}}

{{Beta globulins}}

{{Androgenics}}

{{Estrogenics}}

Category:Glycoproteins