Affinage

SHBG

Sex hormone-binding globulin · UniProt P04278

Length
402 aa
Mass
43.8 kDa
Annotated
2026-04-28
100 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SHBG is a homodimeric glycoprotein that serves as the principal plasma carrier for androgens and estrogens, regulating their bioavailability to target tissues through both passive transport and active receptor-mediated endocytosis. The steroid-binding site resides at the dimer interface, with calcium required for proper dimerization and distinct binding determinants for androgens versus estradiol (PMID:8976560, PMID:24892637). Hepatic SHBG transcription is driven by HNF-4α and modulated by AMPK/adiponectin signaling, TNFα/NF-κB-mediated HNF-4α repression, and the nuclear receptor CAR, while Sertoli cells produce it under FSH control for androgen delivery to germ cells (PMID:1126559, PMID:24828613, PMID:22301786, PMID:28947831). Beyond passive steroid sequestration, SHBG activates a cAMP-dependent membrane signaling pathway that antagonizes estradiol-driven ERK activation and cell proliferation, and incompletely glycosylated intracellular SHBG sustains androgen receptor nuclear localization and amplifies androgen-dependent gene expression (PMID:16700004, PMID:21193555).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1975 High

    Identifying SHBG/ABP as a Sertoli cell product under FSH control established that SHBG is not merely a passive plasma binder but an actively regulated secretory protein with a defined cellular origin in the testis.

    Evidence Testicular fractionation, hypophysectomy with FSH rescue, efferent duct fluid measurements in rat

    PMID:1126559

    Open questions at the time
    • Mechanism of FSH-stimulated transcription not defined
    • Sertoli cell SHBG promoter elements unknown at this stage
  2. 1988 High

    Demonstrating that SHBG-bound steroids are efficiently extracted by testis and prostate in vivo overturned the free-hormone hypothesis for these tissues, showing SHBG itself facilitates steroid delivery.

    Evidence Arterial bolus injection of radiolabeled TeBG/steroids with tissue extraction quantification in anesthetized rats

    PMID:3379140

    Open questions at the time
    • Identity of the membrane receptor mediating SHBG-steroid uptake not determined
    • Mechanism of transcapillary transport unclear
  3. 1991 High

    Discovery of a specific high-affinity membrane receptor for SHBG on prostate and breast cancer cells, and demonstration of receptor-mediated endocytosis through clathrin-coated vesicles to lysosomes, established that SHBG signals and traffics as a ligand rather than acting solely as an extracellular carrier.

    Evidence Radioligand binding, electron microscopy with gold-conjugated TeBG, thymidine incorporation in prostate carcinoma cells; saturable endocytosis in MCF-7 cells

    PMID:1675988 PMID:1958578

    Open questions at the time
    • Molecular identity of the SHBG membrane receptor remains unknown
    • Downstream signaling mechanism not yet characterized
  4. 1992 High

    Establishing that SHBG functions as a homodimer with the steroid-binding site at the dimer interface defined the structural basis for steroid recognition and explained species-specific ligand selectivity.

    Evidence Urea dissociation/renaturation, human-rabbit hybrid dimer formation with radioligand binding

    PMID:8976560

    Open questions at the time
    • Atomic-resolution crystal structure not yet available at this point
    • Role of calcium in dimerization not yet recognized
  5. 1995 High

    Showing that germ cells endocytose Sertoli-derived ABP/SHBG via clathrin-coated pits and that internalized ABP alters spermatocyte protein secretion demonstrated a paracrine signaling role for SHBG within the seminiferous epithelium.

    Evidence Radiolabeled ABP binding/internalization, TEM, 2D-SDS-PAGE of secreted spermatocyte proteins

    PMID:7626507

    Open questions at the time
    • Intracellular fate of internalized ABP in germ cells not fully tracked
    • Downstream signaling cascade in germ cells not identified
  6. 2006 Medium

    Identifying that membrane-bound SHBG activates a cAMP pathway that cross-talks with ERK to oppose estradiol-driven proliferation revealed an active anti-proliferative signaling function independent of simple steroid sequestration.

    Evidence cAMP measurement, ERK activation assays, proliferation/apoptosis assays in MCF-7 breast cancer cells

    PMID:16700004

    Open questions at the time
    • Identity of the G-protein or receptor coupling SHBG to cAMP unknown
    • Relevance in non-breast-cancer estrogen-responsive tissues not tested
    • Single lab finding
  7. 2010 High

    Demonstrating that incompletely glycosylated intracellular SHBG sequesters androgens and sustains androgen receptor nuclear localization established a cell-autonomous amplification mechanism for androgen signaling distinct from extracellular carrier function.

    Evidence Radiolabeled DHT sequestration, androgen-responsive reporter and endogenous gene assays, immunofluorescence of AR localization in mouse PCT cells expressing human SHBG transgene

    PMID:21193555

    Open questions at the time
    • Whether intracellular SHBG acts similarly in prostate cancer cells in vivo is untested
    • Glycosylation site(s) responsible for intracellular retention not mapped
  8. 2012 High

    Elucidating that TNFα suppresses SHBG via NF-κB-mediated repression of HNF-4α (not direct SHBG promoter targeting) explained how inflammation reduces circulating SHBG and linked metabolic syndrome to sex steroid bioavailability.

    Evidence ChIP for NF-κB on HNF-4α promoter, siRNA knockdown and p65 overexpression, luciferase reporters in HepG2 cells

    PMID:22301786

    Open questions at the time
    • Whether other inflammatory cytokines use the same HNF-4α-dependent route is unknown
    • In vivo validation in hepatocyte-specific knockout models lacking
  9. 2014 High

    Identifying adiponectin/AMPK as an upstream activator of SHBG via HNF-4α through reduced hepatic lipid content connected energy-sensing pathways to sex steroid regulation, while comprehensive mutagenesis of naturally occurring SHBG variants revealed how specific residues govern glycosylation, calcium-dependent dimerization, and differential steroid affinity.

    Evidence Adiponectin treatment of HepG2 cells with AMPK inhibition and HNF-4α siRNA; site-directed mutagenesis of eight SNPs with binding, secretion, and calcium-dependence assays

    PMID:24828613 PMID:24892637

    Open questions at the time
    • Structural basis for how hepatic lipid content controls HNF-4α levels is incompletely defined
    • Population-level functional impact of rare SHBG missense variants on disease risk not established
  10. 2017 High

    Demonstrating that the nuclear receptor CAR binds a DR1 element in the SHBG promoter and mediates resveratrol-induced SHBG expression identified a druggable transcriptional regulator of SHBG and was validated in humanized transgenic mice.

    Evidence ChIP for CAR on SHBG promoter, luciferase reporters, resveratrol treatment in HepG2 cells and humanized SHBG/CAR transgenic mice, human liver biopsy correlation

    PMID:28947831

    Open questions at the time
    • Whether CAR agonists beyond resveratrol regulate SHBG in humans is untested
    • Relative contribution of CAR vs. HNF-4α to basal SHBG expression not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular identity of the membrane receptor that mediates SHBG binding, endocytosis, and cAMP signaling remains unknown, preventing a complete mechanistic model of SHBG's cell-surface signaling and steroid-delivery functions.
  • SHBG membrane receptor gene not cloned or identified
  • Structural basis of SHBG-receptor interaction undefined
  • Whether intracellular SHBG and membrane signaling converge on shared downstream targets is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0140104 molecular carrier activity 4 GO:0048018 receptor ligand activity 2
Localization
GO:0005576 extracellular region 5 GO:0005886 plasma membrane 3 GO:0005768 endosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-382551 Transport of small molecules 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1430728 Metabolism 2
Partners
FBLN2HNF4ANR1I3
Complex memberships
SHBG homodimer

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1975 Androgen-binding protein (ABP/SHBG) is produced by Sertoli cells in the testis, not by Leydig cells or germ cells; FSH stimulates its production and it is transported to the epididymis via efferent duct fluid. Testicular fractionation (tubule vs. interstitial preparations), efferent duct fluid vs. lymph measurements, gamma irradiation to ablate germ cells, hypophysectomy followed by FSH rescue Molecular and cellular endocrinology High 1126559
1981 SHBG (TeBG) functions as an androgen transport and carrier protein in plasma, and as androgen-binding protein (ABP) in the seminiferous tubule/epididymis compartment, with both serving to regulate androgen secretion, transport, and cellular absorption. Review of physical characterization studies (binding kinetics, gel filtration, sedimentation) and hormonal regulation experiments Archives of andrology Medium 7025773
1988 TeBG (SHBG)-bound testosterone and estradiol are efficiently cleared across the blood-tubular barrier of the testis and prostate cell membrane in vivo, indicating that TeBG-bound sex steroids (not just free hormone) are bioavailable to Sertoli and prostate cells; extravascular extraction of radiolabeled TeBG was 73–92% in testis and prostate respectively. In vivo arterial bolus injection of radiolabeled testosterone, estradiol, and TeBG in anesthetized rats; tissue extraction quantification The Journal of clinical endocrinology and metabolism High 3379140
1991 SHBG inhibits uptake of DHT into prostate carcinoma cells in a binding-capacity-dependent manner, but also stimulates DNA synthesis (thymidine incorporation) in these cells via a specific high-affinity cell membrane receptor for SHBG; this growth effect is enhanced by testosterone and abolished when SHBG is saturated with DHT. SHBG mRNA (1.9 and 2.8 kb) is expressed endogenously in prostate carcinoma cell lines. Radiolabeled DHT uptake assays, [3H]thymidine incorporation, Northern blot, radioligand binding (cell membrane receptor identification) The Journal of steroid biochemistry and molecular biology High 1958578
1991 TeBG (SHBG) undergoes receptor-mediated endocytosis in human MCF-7 breast cancer cells: it binds to the plasma membrane, enters receptosomes, and traffics through multivesicular endosomes to lysosomes in the Golgi zone; uptake is temperature-dependent, saturable, and competable with unlabeled TeBG. Radiolabeled TeBG uptake assays, electron microscopy with TeBG-gold complexes, pronase surface release experiments, subcellular fractionation with lysosomal marker Endocrinology High 1675988
1992 SHBG is a homodimer; the steroid-binding site is located at the interface between the two subunits. Dissociation in urea and renaturation reconstitutes dimers with normal steroid-binding affinity. A human-rabbit hybrid dimer demonstrates that only one face of the dimer determines specificity for estradiol binding, while the androgen-binding face is shared by both sides. Urea dissociation and renaturation, formation of human-rabbit hybrid dimers, radioligand binding (Kd determination for DHT and estradiol) Protein science High 8976560
1995 Sertoli cell-secreted ABP is endocytosed by germ cells via a clathrin-coated vesicle pathway; germ cells possess a single class of high-affinity binding sites for ABP (Kd ~0.78 nM for rat ABP, ~0.56 nM for human SHBG); internalized ABP stimulates secretion of specific spermatocyte proteins and, together with steroids, induces synthesis of new spermatocyte proteins. Radiolabeled ABP/SHBG binding and internalization, transmission electron microscopy, autoradiography, 2D-SDS-PAGE of secreted proteins, Scatchard analysis of membrane binding sites The Journal of steroid biochemistry and molecular biology High 7626507
1992 SHBG binds to a specific, saturable, high-affinity receptor on rat testicular membranes (Kd 5×10⁻⁸ M at 37°C; capacity 30 pmol/mg protein); solubilization of the receptor increases binding capacity 5-fold and decreases affinity 10-fold; apparent molecular weight of the testicular SHBG receptor is ~174,000 Da. Radioligand binding to testicular membrane preparations, Scatchard analysis, gel filtration of solubilized receptor Molecular and cellular endocrinology Medium 1338724
1998 The SHBG-like region of protein S (a structural homolog domain) is critical for its FV-dependent APC-cofactor activity in FVIIIa degradation; a protein S/Gas6 chimera in which the SHBG-like region was replaced by that of Gas6 lost FV-dependent APC-cofactor activity while retaining ~40–50% activity in FVa degradation. Recombinant chimeric protein construction and functional testing in plasma thrombin generation and FVIIIa degradation assays FEBS letters High 9738926
2004 The D327N (Asp327Asn) polymorphism in SHBG exon 8 delays SHBG half-life and is associated with higher circulating SHBG levels; the pentanucleotide (TAAAA)n repeat in the SHBG 5' UTR influences SHBG transcription in vitro and affects SHBG serum concentrations in a repeat-length-dependent manner (fewer repeats → higher SHBG). RFLP genotyping for D327N, GeneScan for TAAAA repeats, multivariate analysis of serum SHBG levels, luciferase reporter assays (cited in text for in vitro transcription effect) The Journal of clinical endocrinology and metabolism Medium 14764814
2006 SHBG interacts with a specific binding site on MCF-7 breast cancer cell membranes and activates a cAMP-dependent intracellular pathway that inhibits estradiol-mediated ERK activation and cell growth; cross-talk occurs at the MAP kinase level between the membrane-initiated SHBG pathway and the estradiol pathway. Cell membrane binding assays, cAMP measurement, ERK activation assays, cell proliferation/apoptosis assays in MCF-7 cells Hormone and metabolic research Medium 16700004
2010 Incompletely glycosylated (lacking O-linked oligosaccharides and with incomplete N-glycosylation) SHBG accumulates within the cytoplasm of proximal tubule epithelial cells and enhances androgen uptake and sustained androgen receptor nuclear localization, thereby amplifying androgen-dependent gene expression long after steroid withdrawal. Western blotting of cellular vs. secreted SHBG, radiolabeled DHT sequestration assays, luciferase androgen reporter assay, RT-qPCR of endogenous androgen-regulated genes, transcriptome profiling, immunofluorescence of androgen receptor localization in mouse PCT cell line expressing human SHBG transgene Molecular endocrinology High 21193555
2012 TNFα reduces SHBG production in hepatocytes indirectly via NF-κB activation: NF-κB binds to the HNF-4α proximal promoter (which contains three NF-κB binding sites) and represses HNF-4α expression, which in turn reduces SHBG transcription. The human SHBG promoter itself is not directly regulated by NF-κB. Luciferase reporter assays with SHBG and HNF-4α promoter constructs, siRNA knockdown of NF-κB p65, p65 overexpression, chromatin immunoprecipitation (ChIP) for NF-κB binding to HNF-4α promoter in HepG2 cells Molecular endocrinology High 22301786
2014 Adiponectin increases hepatic SHBG production via AMPK activation, which reduces hepatic lipid content (decreasing ACC-driven lipogenesis, increasing ACOX/CPTI-driven fatty acid oxidation) and thereby increases HNF-4α levels; HNF-4α silencing blocks adiponectin-induced SHBG upregulation. HepG2 cell treatment with adiponectin, AMPK inhibition assays, siRNA knockdown of HNF-4α, lipogenesis/fatty acid oxidation enzyme mRNA/protein measurement, triglyceride and FFA quantification, correlation with human liver biopsies Endocrinology High 24828613
2014 The SHBG-like domain (and specifically its laminin G-type 1 subunit, residues Ser283–Val459) of protein S is required for binding to TFPI and enhancing TFPI-mediated inhibition of factor Xa; free protein S (not C4BP-bound) is needed for TFPI cofactor function. Domain-swap chimera screening (44 protein S variants), thrombin generation assay, FXa inhibition assays, surface plasmon resonance binding of protein S to TFPI Blood High 24740810
2014 Eight naturally occurring nonsynonymous SNPs in the N-terminal laminin G-like domain of SHBG alter its production or biochemical properties: O-linked glycosylation at Thr7 is disrupted (T7N), abnormal N-glycosylation limits secretion (G195E), three mutants (R135C, L165M, E176K) bind estradiol with abnormally high affinity, R135C has increased fibulin-2 interaction, two dimer-interface mutants (R123H, R123C) reduce DHT affinity while increasing relative estradiol affinity, and T48I is defective in calcium binding leading to dimerization defects and reduced steroid affinity (all restored by calcium). Site-directed mutagenesis, HepG2 cell expression and secretion assays, radioligand steroid-binding assays, calcium chelation/supplementation experiments, fibulin-2 binding assays Molecular endocrinology High 24892637
2017 Resveratrol increases hepatic SHBG production specifically through human constitutive androstane receptor (CAR), which binds to a direct repeat 1 (DR1) nuclear hormone receptor element in the human SHBG proximal promoter; this was confirmed in humanized SHBG/CAR transgenic mice and correlates with CAR mRNA in human liver biopsies. Chromatin immunoprecipitation (ChIP) for CAR binding to SHBG promoter DR1 element, luciferase reporter assays, resveratrol treatment of HepG2 cells, humanized transgenic mouse experiments, human liver biopsy correlation Scientific reports High 28947831
2004 SHBG mRNA and protein are expressed locally in human granulosa-lutein cells (GLC) of the ovary, demonstrating that SHBG is produced in this tissue beyond the liver and may have a paracrine role in follicular physiology. Immunohistochemistry on human GLC, RT-PCR for full-length SHBG mRNA in cultured and uncultured cells Molecular and cellular endocrinology Medium 15149727
2006 SHBG mRNA and protein are expressed in human cardiac myocytes (in dilated cardiomyopathy biopsies), confirmed by immunocytochemistry on semithin sections, in situ hybridization, and SELDI-TOF mass spectrometry of affinity-purified myocardial extracts, suggesting a local paracrine role for SHBG in regulating steroid bioavailability in the heart. Immunocytochemistry, in situ hybridization, SELDI-TOF mass spectrometry Hormone and metabolic research Medium 16700002
2021 Exogenous SHBG protects palmitate-treated hepatocytes against ER stress by reducing expression of IRE1α, ATF6, CHOP, and BIP, and also regulates lipolytic gene expression in liver tissue ex vivo. Palmitate-treated HepG2 cells and ex vivo liver tissue culture with exogenous SHBG (50–100 nM), western blotting and RT-qPCR for ER stress markers Cells Medium 33808055
2017 SHBG binding capacity for testosterone and estradiol differs between sexes and obesity status: in men testosterone occupies most SHBG binding sites whereas estradiol binding is much lower; morbid obesity reduces SHBG levels and consequently testosterone (but not estradiol) binding, suggesting SHBG is a mixture of at least two functionally distinct hormone-binding globulins with different affinities for the two steroids. Western blotting of plasma SHBG protein, tritium-labeled testosterone and estradiol specific binding assays, ELISA for hormones in plasma from normal-weight and obese men and women European journal of endocrinology Medium 28077498

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 Human endothelial actin-binding protein (ABP-280, nonmuscle filamin): a molecular leaf spring. The Journal of cell biology 471 2391361
1998 Novel anchorage of GluR2/3 to the postsynaptic density by the AMPA receptor-binding protein ABP. Neuron 309 9768844
2005 PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking. Neuron 187 16055064
2009 Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes. Human molecular genetics 178 19933169
2017 Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study. Annals of the rheumatic diseases 148 28584187
2013 Detection of haplotypes associated with prenatal death in dairy cattle and identification of deleterious mutations in GART, SHBG and SLC37A2. PloS one 121 23762392
2000 Modulation of dopamine D(2) receptor signaling by actin-binding protein (ABP-280). Molecular pharmacology 112 10692483
1975 Sertoli cell origin of testicular androgen-binding protein (ABP). Molecular and cellular endocrinology 111 1126559
1992 Targeted disruption of the ABP-120 gene leads to cells with altered motility. The Journal of cell biology 109 1310321
2002 Differential roles for NSF and GRIP/ABP in AMPA receptor cycling. Proceedings of the National Academy of Sciences of the United States of America 108 12011465
2004 Influence of SHBG gene pentanucleotide TAAAA repeat and D327N polymorphism on serum sex hormone-binding globulin concentration in hirsute women. The Journal of clinical endocrinology and metabolism 94 14764814
2009 Sex Hormone-Binding Globulin (SHBG), estradiol and breast cancer. Molecular and cellular endocrinology 87 19770023
1990 Decreased sex hormone binding globulin (SHBG) and insulin-like growth factor binding protein (IGFBP-1) in extreme obesity. Clinical endocrinology 86 1701370
2018 Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial. The Lancet. Oncology 79 29880292
2016 Assessing Analytical Similarity of Proposed Amgen Biosimilar ABP 501 to Adalimumab. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 76 27461107
2014 Adiponectin upregulates SHBG production: molecular mechanisms and potential implications. Endocrinology 74 24828613
1993 Circadian variation in serum free and non-SHBG-bound testosterone in normal men: measurements, and simulation using a mass action model. Clinical endocrinology 74 8370129
2005 Plant villin, lily P-135-ABP, possesses G-actin binding activity and accelerates the polymerization and depolymerization of actin in a Ca2+-sensitive manner. Plant & cell physiology 61 16100394
2003 Interrelationships between plasma testosterone, SHBG, IGF-I, insulin and leptin in prostate cancer cases and controls. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 60 12883384
2003 Plant 115-kDa actin-filament bundling protein, P-115-ABP, is a homologue of plant villin and is widely distributed in cells. Plant & cell physiology 60 14581634
1996 Roles of estrogen and SHBG in prostate physiology. The Prostate 60 8545277
2011 SHBG, sex hormones, and inflammatory markers in older women. The Journal of clinical endocrinology and metabolism 59 21239514
2018 Analytical and functional similarity of Amgen biosimilar ABP 215 to bevacizumab. mAbs 58 29553864
1997 SALIVARY ANDROGEN-BINDING PROTEIN (ABP) MEDIATES SEXUAL ISOLATION IN MUS MUSCULUS. Evolution; international journal of organic evolution 57 28565121
2012 Molecular Mechanism of TNFα-Induced Down-Regulation of SHBG Expression. Molecular endocrinology (Baltimore, Md.) 54 22301786
2018 SHBG expression is correlated with PI3K/AKT pathway activity in a cellular model of human insulin resistance. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 53 29298529
2006 The (TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG levels in women with polycystic ovary syndrome. Human reproduction (Oxford, England) 53 17189294
2011 Association of genetic polymorphisms in ESR2, HSD17B1, ABCB1, and SHBG genes with colorectal cancer risk. Endocrine-related cancer 52 21317201
1988 Serum levels of 3-keto-desogestrel and SHBG during 12 cycles of treatment with 30 micrograms ethinylestradiol and 150 micrograms desogestrel. Contraception 52 2971509
2008 Effects of the contraceptive patch, the vaginal ring and an oral contraceptive on APC resistance and SHBG: a cross-over study. Thrombosis research 50 18829069
1991 Effects of sex hormone binding globulin (SHBG) on human prostatic carcinoma. The Journal of steroid biochemistry and molecular biology 50 1958578
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 : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 49 19064566
2019 Efficacy and Safety of the Biosimilar ABP 215 Compared with Bevacizumab in Patients with Advanced Nonsquamous Non-small Cell Lung Cancer (MAPLE): A Randomized, Double-blind, Phase III Study. Clinical cancer research : an official journal of the American Association for Cancer Research 48 30617139
1991 Receptor-mediated endocytosis of an extracellular steroid-binding protein (TeBG) in MCF-7 human breast cancer cells. Endocrinology 48 1675988
2011 Polymorphisms in the SHBG gene influence serum SHBG levels in women with polycystic ovary syndrome. The Journal of clinical endocrinology and metabolism 47 21252242
1988 Influx of testosterone-binding globulin (TeBG) and TeBG-bound sex steroid hormones into rat testis and prostate. The Journal of clinical endocrinology and metabolism 47 3379140
1987 Behaviour of testosterone, sex hormone binding globulin (SHBG), and cortisol before and after a triathlon competition. International journal of sports medicine 47 3679643
1998 The SHBG-like region of protein S is crucial for factor V-dependent APC-cofactor function. FEBS letters 44 9738926
2014 TFPI cofactor function of protein S: essential role of the protein S SHBG-like domain. Blood 43 24740810
1986 Characteristics of a testosterone-estradiol binding globulin (TEBG) in goldfish serum. Biology of reproduction 43 3814697
2016 Sex Hormone Binding Globulin (SHBG) as a Marker of Clinical Disorders. Collegium antropologicum 42 29139641
2008 Polymorphisms of the SHBG gene contribute to the interindividual variation of sex steroid hormone blood levels in young, middle-aged and elderly men. Clinical endocrinology 41 18681858
1996 Identification and cellular localization of the actin-binding protein ABP-120 from Entamoeba histolytica. Molecular microbiology 41 8971707
2010 A cationic amphiphilic peptide ABP-CM4 exhibits selective cytotoxicity against leukemia cells. Peptides 40 20493915
2016 Demonstration of Functional Similarity of Proposed Biosimilar ABP 501 to Adalimumab. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 39 27422671
2006 Sex hormone-binding globulin (SHBG) and estradiol cross-talk in breast cancer cells. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 39 16700004
2012 Common variants in the sex hormone-binding globulin gene (SHBG) and polycystic ovary syndrome (PCOS) in Mediterranean women. Human reproduction (Oxford, England) 38 23001781
1995 Endocytosis of androgen-binding protein (ABP) by spermatogenic cells. The Journal of steroid biochemistry and molecular biology 38 7626507
2002 Mechanical response of single filamin A (ABP-280) molecules and its role in the actin cytoskeleton. Journal of muscle research and cell motility 37 12785102
1992 Identification of a core motif that is recognized by three members of the HMG class of transcriptional regulators: IRE-ABP, SRY, and TCF-1 alpha. Journal of cellular biochemistry 37 1618927
2008 Rapid bursts of androgen-binding protein (Abp) gene duplication occurred independently in diverse mammals. BMC evolutionary biology 35 18269759
2006 Detection and quantification of 4-ABP adducts in DNA from bladder cancer patients. Carcinogenesis 35 16926175
2020 Effectiveness and safety of adalimumab biosimilar ABP 501 in Crohn's disease: an observational study. Revista espanola de enfermedades digestivas 34 32054272
2004 Effects of combination treatment with losartan and trandolapril on office and ambulatory blood pressures in non-diabetic renal disease: a COOPERATE-ABP substudy. American journal of nephrology 33 15528874
1981 Androgen transport proteins: physical properties, hormonal regulation, and possible mechanism of TeBG and ABP action. Archives of andrology 33 7025773
1997 SHBG region of the anticoagulant cofactor protein S: secondary structure prediction, circular dichroism spectroscopy, and analysis of naturally occurring mutations. Proteins 32 9408945
2017 Modulation of SHBG binding to testosterone and estradiol by sex and morbid obesity. European journal of endocrinology 31 28077498
2011 Circulating testosterone and SHBG concentrations are heritable in women: the Framingham Heart Study. The Journal of clinical endocrinology and metabolism 30 21752884
1975 Testicular androgen-binding protein (ABP): comparison of ABP in rabbit testis and epididymis with a similar androgen-binding protein (TeBG) in rabbit serum. Molecular and cellular endocrinology 30 168102
2019 An open-label extension study to demonstrate long-term safety and efficacy of ABP 501 in patients with rheumatoid arthritis. Arthritis research & therapy 29 30922373
2020 Serum SHBG Is Associated With the Development and Regression of Nonalcoholic Fatty Liver Disease: A Prospective Study. The Journal of clinical endocrinology and metabolism 28 31793624
2003 Characterization of two forms of mouse salivary androgen-binding protein (ABP): implications for evolutionary relationships and ligand-binding function. Biochemistry 28 12795612
2001 Three-dimensional model of the SHBG-like region of anticoagulant protein S: new structure-function insights. Proteins 28 11276089
2016 Effects of sex hormone-binding globulin (SHBG) on androgen bioactivity in vitro. Molecular and cellular endocrinology 26 27576188
2014 Naturally occurring mutants inform SHBG structure and function. Molecular endocrinology (Baltimore, Md.) 26 24892637
2010 Cytoplasmic accumulation of incompletely glycosylated SHBG enhances androgen action in proximal tubule epithelial cells. Molecular endocrinology (Baltimore, Md.) 26 21193555
2006 Expression of androgen-binding protein (ABP) in human cardiac myocytes. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 25 16700002
1992 Binding of sex-hormone-binding globulin (SHBG) to testicular membranes and solubilized receptors. Molecular and cellular endocrinology 25 1338724
1977 Distribution of testosterone-estradiol binding globulin (TeBG) in the higher vertebrates. Endokrinologie 25 562259
2015 Common Variants in the Sex Hormone-Binding Globulin (SHBG) Gene Influence SHBG Levels in Women with Polycystic Ovary Syndrome. Annals of nutrition & metabolism 24 26600064
2002 Association of dopamine D(3) receptors with actin-binding protein 280 (ABP-280). Biochemical pharmacology 23 11911837
2023 The Association between Inflammation, Testosterone and SHBG in men: A cross-sectional Multi-Ethnic Study of Atherosclerosis. Clinical endocrinology 22 37221937
2019 Assessing Analytical and Functional Similarity of Proposed Amgen Biosimilar ABP 980 to Trastuzumab. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 22 30972630
2007 Expression in Escherichia coli and purification of bioactive antibacterial peptide ABP-CM4 from the Chinese silk worm, Bombyx mori. Biotechnology letters 22 17375264
2004 Expression of sex hormone-binding globulin (SHBG) in human granulosa-lutein cells. Molecular and cellular endocrinology 22 15149727
2004 Phosphorylation of actin-binding protein (ABP-280; filamin) by tyrosine kinase p56lck modulates actin filament cross-linking. Cell biology international 22 15566962
2000 Identification of actin binding protein, ABP-280, as a binding partner of human Lnk adaptor protein. Molecular immunology 22 11163396
2020 Circulating SHBG (Sex Hormone-Binding Globulin) and Risk of Ischemic Stroke: Findings From the WHI. Stroke 21 32078494
2017 Resveratrol Increases Hepatic SHBG Expression through Human Constitutive Androstane Receptor: a new Contribution to the French Paradox. Scientific reports 21 28947831
2020 Association between human SHBG gene polymorphisms and risk of PCOS: a meta-analysis. Reproductive biomedicine online 20 33168491
2013 Resistance to APC and SHBG levels during use of a four-phasic oral contraceptive containing dienogest and estradiol valerate: a randomized controlled trial. Journal of thrombosis and haemostasis : JTH 20 23410231
2012 The ovarian response to standard gonadotrophin stimulation depends on FSHR, SHBG and CYP19 gene synergism. Journal of assisted reproduction and genetics 20 22915343
2020 Comparative clinical efficacy and safety of the proposed biosimilar ABP 710 with infliximab reference product in patients with rheumatoid arthritis. Arthritis research & therapy 19 32216829
2017 Expression and characterization of the antimicrobial peptide ABP-dHC-cecropin A in the methylotrophic yeast Pichia pastoris. Protein expression and purification 19 28827052
2013 Androgen receptor CAG repeat length is associated with body fat and serum SHBG in boys: a prospective cohort study. The Journal of clinical endocrinology and metabolism 19 23393169
2009 Effects of polymorphisms of the sex hormone-binding globulin (SHBG) gene on free estradiol and bone mineral density. Bone 19 19679209
2021 Sex Hormone Binding Globulin (SHBG) Mitigates ER Stress in Hepatocytes In Vitro and Ex Vivo. Cells 18 33808055
2020 The hepatic lipidome and HNF4α and SHBG expression in human liver. Endocrine connections 18 33064664
1975 Testicular androgen binding protein (ABP) - a parameter of Sertoli cell secretory function. Current topics in molecular endocrinology 18 18322
2017 Selective cytotoxicity of the antibacterial peptide ABP-dHC-Cecropin A and its analog towards leukemia cells. European journal of pharmacology 17 28347740
2007 Associations of serum sex hormone binding globulin (SHBG) levels with SHBG gene polymorphisms in the CARDIA Male Hormone Study. American journal of epidemiology 17 18056923
1996 Direct evidence for the localization of the steroid-binding site of the plasma sex steroid-binding protein (SBP or SHBG) at the interface between the subunits. Protein science : a publication of the Protein Society 17 8976560
2014 Molecular structure, chemical synthesis, and antibacterial activity of ABP-dHC-cecropin A from drury (Hyphantria cunea). Peptides 16 25241628
2013 The role of retrotransposons in gene family expansions: insights from the mouse Abp gene family. BMC evolutionary biology 16 23718880
1993 The amino acid sequence of the alpha subunit of mouse salivary androgen-binding protein (ABP), with a comparison to the partial sequence of the beta subunit and to other ligand-binding proteins. Biochemical genetics 16 8274137
2019 Bioactivation of the tobacco carcinogens 4-aminobiphenyl (4-ABP) and 2-amino-9H-pyrido[2,3-b]indole (AαC) in human bladder RT4 cells. Archives of toxicology 15 31203411
2017 Studies of an Androgen-Binding Protein Knockout Corroborate a Role for Salivary ABP in Mouse Communication. Genetics 15 28159752
2016 Contribution of polymorphisms in ESR1, ESR2, FSHR, CYP19A1, SHBG, and NRIP1 genes to migraine susceptibility in Turkish population. Journal of genetics 15 27019440
2020 Analytical and Functional Similarity Assessment of ABP 710, a Biosimilar to Infliximab Reference Product. Pharmaceutical research 14 32476063
1999 ABP: a novel AMPA receptor binding protein. Annals of the New York Academy of Sciences 14 10414337