Sex hormone-binding globulin

SHBG
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1LHW, 1D2S, 1F5F, 1KDK, 1KDM, 1LHN, 1LHO, 1LHU, 1LHV
Identifiers
Aliases	SHBG, ABP, SBP, TEBG, sex hormone binding globulin, Sex hormone-binding globulin
External IDs	OMIM: 182205 MGI: 98295 HomoloGene: 813 GeneCards: SHBG
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p13.1 Start 7,613,946 bp[1] End 7,633,382 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 B3|11 42.86 cM Start 69,505,630 bp[2] End 69,508,731 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver duodenum jejunal mucosa left adrenal gland kidney prefrontal cortex stromal cell of endometrium nucleus accumbens putamen caudate nucleus Top expressed in morula spermatocyte testicle entorhinal cortex abdominal wall tracheobronchial tree spermatid seminiferous tubule ovary yolk sac More reference expression data BioGPS More reference expression data
Orthologs Species Human Mouse Entrez 6462 20415 Ensembl ENSG00000129214 ENSMUSG00000005202 UniProt P04278 P97497 RefSeq (mRNA) NM_001040 NM_001146279 NM_001146280 NM_001146281 NM_001289113 NM_001289114 NM_001289115 NM_001289116 NM_011367 RefSeq (protein) NP_001031 NP_001139751 NP_001139752 NP_001139753 NP_001276042 NP_001276043 NP_001276044 NP_001276045 NP_035497 Location (UCSC) Chr 17: 7.61 – 7.63 Mb Chr 11: 69.51 – 69.51 Mb PubMed search [3] [4]
Wikidata
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Androgen-binding protein, Sex hormone-binding globulin
Identifiers
Symbol	SHBG
Alt. symbols	ABP
NCBI gene	6462
HGNC	10839
OMIM	182205
RefSeq	NM_001040
UniProt	P04278
Other data
Locus	Chr. 17 p13-p12
Search for Structures Swiss-model Domains InterPro

Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it is called androgen-binding protein (ABP).^[5][6]

Other steroid hormones such as progesterone, cortisol, and other corticosteroids are bound by transcortin. SHBG is found in all vertebrates apart from birds.^[7]

Function

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^[6] 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.^[8] DHT binds to SHBG with about 5 times the affinity of testosterone and about 20 times the affinity of estradiol.^[9] Dehydroepiandrosterone (DHEA) is weakly bound to SHBG, but dehydroepiandrosterone sulfate is not bound to SHBG.^[8] Androstenedione is not bound to SHBG either, and is instead bound solely to albumin.^[10] Estrone sulfate and estriol are also poorly bound by SHBG.^[11] Less than 1% of progesterone is bound to SHBG.^[12]

SHBG levels are usually about twice as high in women than in men.^[9] In women, SHBG serves to limit exposure to both androgens and estrogens.^[9] Low SHBG levels in women have been associated with hyperandrogenism and endometrial cancer due to heightened exposure to androgens and estrogens, respectively.^[9] During pregnancy, due to activation of SHBG production in the liver by high estrogen levels, SHBG levels increase by five-fold to ten-fold.^[9] The high SHBG levels during pregnancy may serve to protect the mother from exposure to fetal androgens that escape metabolism by the placenta.^[9] A case report of severe hyperandrogenism in a pregnant woman due to a rare instance of genetic SHBG deficiency illustrates this.^[9][13]

Biochemistry

Biosynthesis

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.^[14] Testes-produced SHBG is called androgen-binding protein.

Gene

The gene for SHBG is called Shbg located on chromosome 17^[14] on the short arm between the bands 17p12→p13.^[15] 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.^[16] 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.^[17]

Polymorphisms

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-glycosilation site, and so an extra sugar can be attached. This results in a longer circulation half-life for the protein, and raised levels. A health effect is a lowered risk of endometrial cancer, and another is an increased risk of systemic lupus erythematosus.^[18]

Rs6258 also called Ser156Pro is at position 7631360 on the Chromosome 17.

Rs727428 position 7634474 is in several percent of humans.^[19]

(TAAAA)(n) is five base pairs that repeats a variable number of times on the opposite DNA strand.^[20]

Promoter activation

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 stimulate production. Competing with HNF4A at a third site on the promoter is PPARG-2 which reduces copying the gene to RNA. If HNF4A level is low then COUP-TF binds to the first site and turns off production of SHBG.^[7]

Protein

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 but that has different oligosaccharides attached and is produced in testes.^[14]

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.^[7] 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.^[7] The steroid binding LG domain is coded by exons 2 to 5.^[7] A linker region joins the two LG domains together.^[7]

When first produced the SHBG precursor has a leading signal peptide attached with 29 amino acids. The remaining peptide has 373 amino acids.^[21] There are two sulfur bridges.

The sugars are attached at two different N-glycosylation points on asparagine (351 and 367) and one O-glycosylation (7) point on threonine.^[21]

Metals

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.^[7]

Regulation

SHBG has both enhancing and inhibiting hormonal influences 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 Interleukin reduce SHBG, whereas insulin does not. As an 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^[22] was downregulation of HNF4, hepatocyte nuclear factor 4.^{[23][24][25][26]}

Blood values

Reference ranges for blood tests for SHBG have been developed:^[27][28]

Population	Range
Adult female, premenopausal	40–120 nmol/L
Adult female, postmenopausal	28–112 nmol/L
Adult male	20–60 nmol/L
Infant (1–23 months)	60–252 nmol/L
Prepubertal (2 years–8 years)	72–220 nmol/L
Pubertal female	36–125 nmol/L
Pubertal male	16–100 nmol/L

Clinical significance

High or low levels

Levels of sex hormones and SHBG during pregnancy in women.^[29]

Levels of SHBG and estradiol during pregnancy in women.^[30] For SHBG the lines are the mean and 95th percentile levels while the points are individual measurements.^[30] For estradiol the line is the mean level.^[30] The dashed parts of the lines are extrapolated.^[30]

SHBG binding capacity during pregnancy in women.^[31]

SHBG levels are decreased by androgens, administration of anabolic steroids,^[32] polycystic ovary syndrome, hypothyroidism, obesity, Cushing's syndrome, and acromegaly. Low SHBG levels increase the probability of Type 2 Diabetes.^[33] SHBG levels increase with estrogenic states (oral contraceptives), pregnancy, hyperthyroidism, cirrhosis, anorexia nervosa, and certain drugs. Long-term calorie restriction of more than 50 percent (in rodents) increases SHBG, while lowering free and total testosterone and estradiol. DHEA-S, which lacks affinity for SHBG, is not affected by calorie restriction.^[34] Polycystic Ovarian Syndrome is associated with insulin resistance and excess insulin lowers SHBG, which increases free testosterone levels.^[35]

In the womb 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.^[7] The change at puberty is triggered by growth hormone, and its pulsatility differs in boys and girls.^{[clarification needed]} In pregnant women in the third trimester of pregnancy the SHBG level escalates to five to ten times the usual level for a woman.^[7][9] A hypothesis is that this protects against the effect of hormone produced by the fetus.^[7]

Obese girls are more likely to have an early menarche due to lower levels of SHBG.^[7] Anorexia or a lean physique in women leads to higher SHBG levels, which in turn can lead to amenorrhea.^[7]

Type 2 diabetes

Reduced levels of SHBG and also certain polymorphisms of the SHBG gene are implicated in the development of insulin resistance and type 2 diabetes.^[36] 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.^[37]

Coagulation

SHBG is a useful correlate and indirect marker of estrogen-induced procoagulation and by extension thrombosis, for instance with birth control pills.^[38][39][40]

Medications

Oral contraceptives containing ethinylestradiol can increase SHBG levels by 2- to 4-fold and decrease free testosterone concentrations by 40 to 80% in women.^[41] They can be used to treat symptoms of hyperandrogenism like acne and hirsutism.^[41][9] Some oral contraceptives, namely those containing high doses of ethinylestradiol (which have been discontinued and are no longer marketed), can increase SHBG levels by as much as 5- to 10-fold.^[9]

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.^[42][43][44] 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.^[42][45]

Selective androgen receptor modulators (SARMs) also reduce SHBG.^[46]

Affinities of 70 medications for SHBG and CBG^[42]

Compound	Structure	SHBG RBA (%)	SHBG K (10^6 M^−1)	CBG RBA (%)	CBG K (10^6 M^−1)
Aminoglutethimide	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Androstanolone	Steroidal	220	5500	1.3	0.83
Betamethasone	Steroidal	<0.01	<0.2	<0.1	<0.1
Cholecalciferol	Steroidal	<0.01	<0.2	<0.1	<0.1
Cimetidine	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Clomifene	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Cortisol (hydrocortisone)	Steroidal	0.13	1.6	100	76
Cortisone acetate	Steroidal	0.10	1.2	<0.1	<0.1
Cyproterone acetate	Steroidal	0.10	1.2	<0.1	<0.1
Danazol	Steroidal	18	240	10	6.5
Dexamethasone	Steroidal	<0.01	<0.2	<0.1	<0.1
Diazoxide	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Diethylstilbestrol	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Digitoxin	Steroidal	<0.01	<0.2	<0.1	<0.1
Digoxin	Steroidal	<0.01	<0.2	<0.1	<0.1
DL-DOPA	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Dopamine	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Enclomiphene	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Epinephrine	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Estradiol	Steroidal	49	680	<0.1	<0.1
Estradiol benzoate	Steroidal	0.70	8.6	<0.1	<0.1
Ethinylestradiol	Steroidal	0.80	9.9	<0.1	<0.1
Ethisterone	Steroidal	55	780	0.33	0.21
Fludrocortisone	Steroidal	<0.01	<0.2	0.74	0.47
Fluoxymesterone	Steroidal	4.8	60	<0.1	<0.1
Flutamide	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Homovanillic acid	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Hydrocortisone hemisuccinate	Steroidal	<0.01	<0.2	8.7	5.6
Indometacin	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Levonorgestrel	Steroidal	31	420	<0.1	<0.1
Medroxyprogesterone	Steroidal	0.15	1.9	13	8.1
Medroxyprogesterone acetate	Steroidal	0.08	1.0	6.5	4.2
Melatonin	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Mesterolone	Steroidal	180	3600	<0.1	<0.1
Mestranol	Steroidal	<0.01	<0.2	<0.1	<0.1
Methoxytryptophol	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Methyldopa	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Methylserotonin	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Methyltestosterone	Steroidal	39	530	<0.1	<0.1
Metiamide	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Metribolone	Steroidal	1.7	21	0.36	0.23
Metyrapone	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Mexrenone	Steroidal	<0.01	<0.2	<0.1	<0.1
Nafoxidine	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Nandrolone	Steroidal	5.8	72	0.10	0.63
Norepinephrine	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Norethisterone	Steroidal	11	140	0.28	0.18
Noretynodrel	Steroidal	1.3	16	0.16	0.10
Normetanephrine	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Phenytoin	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Potassium canrenoate	Steroidal	0.18	2.2	0.83	0.53
Prednisolone	Steroidal	0.04	0.49	59	41
Prednisone	Steroidal	0.17	2.1	5.0	3.2
Progesterone	Steroidal	0.71	8.8	36	24
Promegestone	Steroidal	0.007	0.09	0.40	0.25
Prorenone	Steroidal	8.2	100	<0.1	<0.1
Reserpine	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Rifampin	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Serotonin	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Spironolactone	Steroidal	0.03	0.37	<0.1	<0.1
Tamoxifen	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Testolactone	Steroidal	<0.01	<0.2	<0.1	<0.1
Testosterone	Steroidal	100	1600	8.3	5.3
Testosterone enanthate	Steroidal	0.007	0.086	<0.1	<0.1
7α-Thioprogesterone	Steroidal	0.06	0.74	36	24
7α-Thiospironolactone	Steroidal	0.59	7.3	<0.1	<0.1
Thyroxine	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Triiodothyronine	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Trimethyltrienolone	Steroidal	0.90	11	0.11	0.07
Vanillylmandelic acid	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
Zuclomifene	Nonsteroidal	<0.01	<0.2	<0.1	<0.1
The reference ligands (100%) for the RBATooltip relative binding affinity (%) values were testosterone for SHBG and cortisol for CBGTooltip corticosteroid-binding globulin.

Affinities of 21 progestins for SHBG and CBG^[44]^[47]

Progestogen	SHBG (%)	CBG (%)
17α-Allyl-19-nortestosterone	<1	?
Allylestrenol	<1	?
Chlormadinone acetate	<1	<1
Cyproterone acetate	<1	<1
Desogestrel	<1	<1
Dienogest	<1	<1
Drospirenone	<1	<1
Etonogestrel	15	<1
Gestodene	40	<1
Levonorgestrel	50	<1
Medroxyprogesterone acetate	<1	<1
Megestrol acetate	<1	<1
Nomegestrol acetate	<1	<1
Norelgestromin	<1	?
Norethisterone	16	<1
Noretynodrel	<1	<1
Norgestimate	<1	<1
Progesterone	<1	36
Promegestone	<1	<1
Segesterone acetate	<1	?
Δ^4-Tibolone	1	<1
Values are RBAsTooltip relative binding affinities (%). The reference ligand (100%) for SHBG was dihydrotestosterone and for CBGTooltip corticosteroid-binding globulin was cortisol.

Affinities of 14 AAS for SHBG^[43]

Compound	SHBG (%)
5α-Androstane-3β,17β-diol	17
5β-Androstane-3α,17β-diol	5
Dihydrotestosterone	100
Ethylestrenol	<1
Fluoxymesterone	<1
Mesterolone	440
Metandienone	2
Metenolone	3
Methyltestosterone	5
Metribolone	<1
Nandrolone	1
Oxymetholone	<1
Stanozolol	1
Testosterone	19
Values are RBAsTooltip relative binding affinities (%). The reference ligand (100%) for SHBG was dihydrotestosterone.

Affinities of 41 steroids for SHBG^[48]

Compound	SHBG (%)
3β-Androstanediol	100
Androstenediol	77
Bolandiol	24
Dihydroethisterone	100
Dihydroethyltestosterone	18–21
Dihydromethylandrostenediol	77
Dihydronandrolone	44
Dihydrotestosterone	100
Dihydrotrestolone	47
4,17α-Dimethyltestosterone	97
Drostanolone	39
Ethisterone	92
Fluoxymesterone	3
11-Ketodihydrotestosterone	0
Medroxyprogesterone acetate	16
Megestrol acetate	0
Mestanolone	84
Methasterone	58
Methyl-1-testosterone	69
Methylandrostenediol	40
Methyltestosterone	64
Mibolerone	6
Nandrolone	16
Nandrolone decanoate	0
Nandrolone phenylpropionate	0
Norethandrolone	3
Norethisterone	21
Normethandrone	7
Oxandrolone	0
Oxymetholone	3
Progesterone	13
Stanozolol	36
1-Testosterone	98
Testosterone	82
Testosterone benzoate	8
Testosterone cypionate	6
Testosterone enanthate	9
Δ^4-Tibolone	8
Trestolone	12
Trestolone enanthate	12
Vinyltestosterone	36
Values are RBAsTooltip relative binding affinities (%). The reference ligand (100%) for SHBG was dihydrotestosterone.

Affinities of 11 steroids for SHBG and CBG^[49]

Compound	SHBGTooltip Sex hormone-binding globulin (%)	CBGTooltip Corticosteroid binding globulin (%)
Aldosterone	<0.2	6.0
Corticosterone	<0.2	107
Cortisol	<0.2	100
Dexamethasone	<0.2	<0.1
Dihydrotestosterone	100	0.8
Estradiol	8.7	<0.1
Metribolone	0.2	<0.1
Moxestrol	<0.2	<0.1
Progesterone	<0.2	25
Promegestone	<0.2	0.9
Testosterone	26	3
Values are RBAsTooltip relative binding affinities (%). The reference ligand (100%) for SHBG was dihydrotestosterone and for CBGTooltip corticosteroid-binding globulin was cortisol.

Affinities of 9 estrogens for SHBG^[44]^[50]

Compound	RBATooltip Relative binding affinity to SHBGTooltip sex hormone-binding globulin (%)	Bound to SHBG (%)	Bound to albumin (%)
17β-Estradiol	50	37	61
Estrone	12	16	80
Estriol	0.3	1	91
Estrone sulfate	0	0	99
17β-Dihydroequilin	30	?	?
Equilin	8	26	13
17β-Dihydroequilin sulfate	0	?	?
Equilin sulfate	0	?	?
Δ^8-Estrone	?	?	?
The reference ligand (100%) for the SHBG RBATooltip relative binding affinity (%) values was testosterone.

Endogenous steroids

Measurement

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.

Affinity and binding

Affinities of endogenous steroids for SHBG and plasma protein binding^[51]

Steroid	SHBG affinity		Plasma protein binding in men					Plasma protein binding in women (follicular phase)
	RBA (%)	K (10^6 M^−1)	Total (nM)	Unbound (%)	SHBG (%)	CBG (%)	Albumin (%)	Total (nM)	Unbound (%)	SHBG (%)	CBG (%)	Albumin (%)
Aldosterone	0.017	0.21	0.35	37.1	0.10	21.2	41.6	0.24	36.8	0.23	21.9	41.2
3α-Androstanediol	82	1300	0.41	0.85	13.7	<0.1	85.5	0.068	0.71	27.9	<0.1	71.4
Androstenediol	97	1500	4.3	3.24	60.4	<0.1	36.3	2.4	1.73	78.8	<0.1	19.4
Androstenedione	2.3	29	4.1	7.85	2.82	1.37	88.0	5.4	7.54	6.63	1.37	84.5
Androsterone	1.1	14	2.0	4.22	0.73	0.52	94.5	1.5	4.18	1.77	0.54	93.5
Corticosterone	0.18	2.2	12	3.39	0.09	77.5	19.0	7.0	3.28	0.22	78.1	18.4
Cortisol	0.13	1.6	400	3.91	0.08	89.5	6.57	400	3.77	0.18	89.7	6.33
Cortisone	0.22	2.7	72	16.2	0.54	38.0	45.3	54	15.8	1.30	38.6	44.3
Dehydroepiandrosterone	5.3	66	24	4.13	3.38	<0.1	92.4	17	3.93	7.88	<0.1	88.1
11-Deoxycorticosterone	1.9	24	0.20	2.69	0.80	36.4	60.1	0.12	2.62	1.91	36.9	58.6
11-Deoxycortisol	1.3	16	1.4	3.37	0.67	77.1	18.9	0.60	3.24	1.57	77.1	18.1
Dihydrotestosterone	220	5500	1.7	0.88	59.7	0.22	39.2	0.65	0.47	78.4	0.12	21.0
Estradiol	49	680	0.084	2.32	19.6	<0.1	78.0	0.29	1.81	37.3	<0.1	60.8
Estriol	0.35	4.3	0.037	8.15	0.44	<0.2	91.3	0.10	8.10	1.06	<0.2	90.7
Estrone	12	150	0.081	3.96	7.37	<0.1	88.6	0.23	3.58	16.3	<0.1	80.1
Etiocholanolone	0.11	1.4	1.3	8.15	0.14	0.44	91.3	1.2	8.13	0.35	0.46	91.1
Pregnenolone	1.1	14	2.4	2.87	0.50	0.16	96.5	2.2	2.85	1.21	0.16	95.8
17α-Hydroxypregnenolone	0.19	2.3	5.4	4.27	0.12	<0.1	95.5	3.5	4.26	0.30	<0.1	95.4
Progesterone	0.71	8.8	0.57	2.39	0.26	17.2	80.1	0.65	2.36	0.63	17.7	79.3
17α-Hydroxyprogesterone	0.8	9.9	5.4	2.50	0.31	41.3	55.9	1.8	2.44	0.73	42.1	54.7
Testosterone	100	1600	23	2.23	44.3	3.56	49.9	1.3	1.36	66.0	2.26	30.4
In men, the concentrations of SHBG, CBG, and albumin were 28 nM, 0.7 μM, and 0.56 mM, respectively. In women, the concentrations of SHBG, CBG, and albumin were 37 nM, 0.7 μM, and 0.56 mM, respectively.

Synonyms

SHBG has been known under a variety of different names including:^[52][53][54]

• 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)

References

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Further reading

• Rosner W, Hryb DJ, Khan MS, Nakhla AM, Romas NA (1999). "Sex hormone-binding globulin mediates steroid hormone signal transduction at the plasma membrane". The Journal of Steroid Biochemistry and Molecular Biology. 69 (1–6): 481–5. doi:10.1016/S0960-0760(99)00070-9. PMID 10419028. S2CID 6499033.
• Power SG, Bocchinfuso WP, Pallesen M, Warmels-Rodenhiser S, Van Baelen H, Hammond GL (October 1992). "Molecular analyses of a human sex hormone-binding globulin variant: evidence for an additional carbohydrate chain". The Journal of Clinical Endocrinology and Metabolism. 75 (4): 1066–70. doi:10.1210/jcem.75.4.1400872. PMID 1400872.
• Gershagen S, Lundwall A, Fernlund P (November 1989). "Characterization of the human sex hormone binding globulin (SHBG) gene and demonstration of two transcripts in both liver and testis". Nucleic Acids Research. 17 (22): 9245–58. doi:10.1093/nar/17.22.9245. PMC 335128. PMID 2587256.
• Hammond GL, Underhill DA, Rykse HM, Smith CL (November 1989). "The human sex hormone-binding globulin gene contains exons for androgen-binding protein and two other testicular messenger RNAs". Molecular Endocrinology. 3 (11): 1869–76. doi:10.1210/mend-3-11-1869. PMID 2608061.
• Que BG, Petra PH (July 1987). "Characterization of a cDNA coding for sex steroid-binding protein of human plasma". FEBS Letters. 219 (2): 405–9. doi:10.1016/0014-5793(87)80261-2. PMID 2956125. S2CID 21654093.
• Gershagen S, Fernlund P, Lundwall A (August 1987). "A cDNA coding for human sex hormone binding globulin. Homology to vitamin K-dependent protein S". FEBS Letters. 220 (1): 129–35. doi:10.1016/0014-5793(87)80890-6. PMID 2956126. S2CID 13166151.
• Walsh KA, Titani K, Takio K, Kumar S, Hayes R, Petra PH (November 1986). "Amino acid sequence of the sex steroid binding protein of human blood plasma". Biochemistry. 25 (23): 7584–90. doi:10.1021/bi00371a048. PMID 3542030.
• Hammond GL, Robinson PA, Sugino H, Ward DN, Finne J (April 1986). "Physicochemical characteristics of human sex hormone binding globulin: evidence for two identical subunits". Journal of Steroid Biochemistry. 24 (4): 815–24. doi:10.1016/0022-4731(86)90442-5. PMID 3702459.
• Hardy DO, Cariño C, Catterall JF, Larrea F (April 1995). "Molecular characterization of a genetic variant of the steroid hormone-binding globulin gene in heterozygous subjects". The Journal of Clinical Endocrinology and Metabolism. 80 (4): 1253–6. doi:10.1210/jcem.80.4.7714097. PMID 7714097.
• 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 (July 1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes". Nature Genetics. 22 (3): 231–8. doi:10.1038/10290. PMID 10391209. S2CID 195213008.
• Grishkovskaya I, Avvakumov GV, Sklenar G, Dales D, Hammond GL, Muller YA (February 2000). "Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain". The EMBO Journal. 19 (4): 504–12. doi:10.1093/emboj/19.4.504. PMC 305588. PMID 10675319.
• Hogeveen KN, Talikka M, Hammond GL (September 2001). "Human sex hormone-binding globulin promoter activity is influenced by a (TAAAA)n repeat element within an Alu sequence". The Journal of Biological Chemistry. 276 (39): 36383–90. doi:10.1074/jbc.M104681200. PMID 11473114.
• Hryb DJ, Nakhla AM, Kahn SM, St George J, Levy NC, Romas NA, Rosner W (July 2002). "Sex hormone-binding globulin in the human prostate is locally synthesized and may act as an autocrine/paracrine effector". The Journal of Biological Chemistry. 277 (29): 26618–22. doi:10.1074/jbc.M202495200. PMID 12015315.
• Raineri M, Catalano MG, Hammond GL, Avvakumov GV, Frairia R, Fortunati N (March 2002). "O-Glycosylation of human sex hormone-binding globulin is essential for inhibition of estradiol-induced MCF-7 breast cancer cell proliferation". Molecular and Cellular Endocrinology. 189 (1–2): 135–43. doi:10.1016/S0303-7207(01)00725-0. PMID 12039072. S2CID 24123789.
• Grishkovskaya I, Avvakumov GV, Hammond GL, Muller YA (May 2002). "Resolution of a disordered region at the entrance of the human sex hormone-binding globulin steroid-binding site". Journal of Molecular Biology. 318 (3): 621–6. doi:10.1016/S0022-2836(02)00169-9. PMID 12054810.
• 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 (December 2008). "Identification of common variants in the SHBG gene affecting sex hormone-binding globulin levels and breast cancer risk in postmenopausal women". Cancer Epidemiology, Biomarkers & Prevention. 17 (12): 3490–8. doi:10.1158/1055-9965.EPI-08-0734. PMC 2660245. PMID 19064566.
• Trkiehl (2011). "SHBG - SNPedia". Retrieved 13 July 2014.

External links

• Overview of all the structural information available in the PDB for UniProt: P04278 (Sex hormone-binding globulin) at the PDBe-KB.
• Androgen-Binding+Protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Ensembl Gene ref Protein ref