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Geoffrey L. Hammond - One of the best experts on this subject based on the ideXlab platform.
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GL: Diverse roles for sex Hormone-Binding globulin in reproduction
2016Co-Authors: Geoffrey L. HammondAbstract:Sex Hormone-Binding globulin (SHBG) transports androgens and estrogens in blood and regulates their access to target tissues. Hepatic production of SHBG fluctuates throughout the life cycle and is influenced primarily by metabolic and hormonal factors. Genetic differences also contribute to interindividual variations in plasma SHBG levels. In addition to controlling the plasma distribution, metabolic clearance, and bioavailability of sex steroids, SHBG accumulates in the extravascular compart-ments of some tissues and in the cytoplasm of specific epithelial cells, where it exerts novel effects on androgen and estrogen action. In mammals, the gene-encoding SHBG is expressed primarily in the liver but also at low levels in other tissues, including the testis. In subprimate species, Shbg expression in Sertoli cells is under the control of follicle-stimulating Hormone and produces the androgen-Binding protein that influences androgen actions in the seminiferous tubules and epididymis. In humans, the SHBG gene is not expressed in Sertoli cells, but its expression in germ cells produces an SHBG isoform that accumulates in the acrosome. In fish, Shbg is produced by the liver but has a unique function in the gill as a portal for natural steroids and xenobiotics, including synthetic steroids. However, salmon have retained a second, poorly conserved Shbg gene that is expressed only in ovary, muscle, and gill and that likely exerts specialized functions in these tissues. The present review compares the production and functions of SHBG in different species and its diverse effects on reproduction. male reproductive tract, mechanisms of Hormone action, sperm, steroid Hormones/steroid Hormone receptors, testi
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Diverse Roles for Sex Hormone-Binding Globulin in Reproduction
Biology of Reproduction, 2011Co-Authors: Geoffrey L. HammondAbstract:Sex Hormone-Binding globulin (SHBG) transports androgens and estrogens in blood and regulates their access to target tissues. Hepatic production of SHBG fluctuates throughout the life cycle and is influenced primarily by metabolic and hormonal factors. Genetic differences also contribute to interindividual variations in plasma SHBG levels. In addition to controlling the plasma distribution, metabolic clearance, and bioavailability of sex steroids, SHBG accumulates in the extravascular compartments of some tissues and in the cytoplasm of specific epithelial cells, where it exerts novel effects on androgen and estrogen action. In mammals, the gene-encoding SHBG is expressed primarily in the liver but also at low levels in other tissues, including the testis. In subprimate species, Shbg expression in Sertoli cells is under the control of follicle-stimulating Hormone and produces the androgen-Binding protein that influences androgen actions in the seminiferous tubules and epididymis. In humans, the SHBG gene is not expressed in Sertoli cells, but its expression in germ cells produces an SHBG isoform that accumulates in the acrosome. In fish, Shbg is produced by the liver but has a unique function in the gill as a portal for natural steroids and xenobiotics, including synthetic steroids. However, salmon have retained a second, poorly conserved Shbg gene that is expressed only in ovary, muscle, and gill and that likely exerts specialized functions in these tissues. The present review compares the production and functions of SHBG in different species and its diverse effects on reproduction.
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sex Hormone Binding globulin in fish gills is a portal for sex steroids breached by xenobiotics
Endocrinology, 2008Co-Authors: Solange Miguelqueralt, Geoffrey L. HammondAbstract:As in most vertebrates, plasma sex Hormone-Binding globulin (SHBG) is produced in fish liver and regulates sex steroid access to target tissues. Low levels of SHBG mRNA are present in zebra fish gills but are unlikely to account for the high amounts of immunoreactive SHBG in filaments and lamellae. Although the uptake of steroids by fish from water has been reported to correlate with their affinity for SHBG, it is not known how this occurs. Our studies of zebra fish SHBG have revealed its preference for biological active androgen (testosterone), as well as for androstenedione, a sex steroid precursor that also acts as a pheromone in some fish. In addition to natural steroids, zebra fish SHBG has a high affinity for synthetic steroids, such as ethinylestradiol and progestins (levonorgestrel and norethindrone), that are present in waste water systems. Because steroids can pass across fish gills, we examined whether SHBG serves as a portal for natural and synthetic steroids controlling their flux between the...
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estetrol does not bind sex Hormone Binding globulin or increase its production by human hepg2 cells
Climacteric, 2008Co-Authors: Geoffrey L. Hammond, M Visser, K N Hogeveen, H Coelingh J T BenninkAbstract:Objectives To determine whether human sex Hormone Binding globulin (SHBG) binds estetrol (E4), and to assess whether E4 stimulates the production of SHBG by human hepatocytes.Methods Competitive ligand Binding assays have been used to assess the relative Binding affinity of E4 to human SHBG using either [3H]5α-dihydrotestosterone or [3H]estradiol as labeled ligands. The effect of E4 on the production of SHBG has been assessed by a fluoroimmunometric assay in wild-type human HepG2 cells and in human Hep89 cells that over-express the human estrogen receptor (ER) α, and compared to the effect of ethinylestradiol, estradiol and estriol.Results There was no detectable Binding of E4 to the human SHBG steroid-Binding sites. By contrast, testosterone and estradiol were bound with high affinity and the synthetic estrogen ethinylestradiol was found to bind SHBG with low affinity. Estetrol does not stimulate ERα-mediated increases in SHBG production by HepG2 or Hep89 cells, in contrast to ethinylestradiol, estradiol...
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monosaccharide induced lipogenesis regulates the human hepatic sex Hormone Binding globulin gene
Journal of Clinical Investigation, 2007Co-Authors: David M Selva, Kevin N Hogeveen, Sheila M Innis, Geoffrey L. HammondAbstract:The liver produces plasma sex Hormone–Binding globulin (SHBG), which transports sex steroids and regulates their access to tissues. In overweight children and adults, low plasma SHBG levels are a biomarker of the metabolic syndrome and its associated pathologies. Here, we showed in transgenic mice and HepG2 hepatoblastoma cells that monosaccharides (glucose and fructose) reduce human SHBG production by hepatocytes. This occurred via a downregulation of hepatocyte nuclear factor–4α (HNF-4α) and replacement of HNF-4α by the chicken OVA upstream promoter–transcription factor 1 at a cis-element within the human SHBG promoter, coincident with repression of its transcriptional activity. The dose-dependent reduction of HNF-4α levels in HepG2 cells after treatment with glucose or fructose occurred in concert with parallel increases in cellular palmitate levels and could be mimicked by treatment with palmitoyl-CoA. Moreover, inhibition of lipogenesis prevented monosaccharide-induced downregulation of HNF-4α and reduced SHBG expression in HepG2 cells. Thus, monosaccharide-induced lipogenesis reduced hepatic HNF-4α levels, which in turn attenuated SHBG expression. This provides a biological explanation for why SHBG is a sensitive biomarker of the metabolic syndrome and the metabolic disturbances associated with increased fructose consumption.
Marian Kochman - One of the best experts on this subject based on the ideXlab platform.
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Juvenile Hormone Binding protein traffic - Interaction with ATP synthase and lipid transfer proteins.
Biochimica et Biophysica Acta - Molecular Cell Research, 2009Co-Authors: Marta Zalewska, Andrzej Ożyhar, Agata Kochman, Jean-pierre Estève, Frédéric Lopez, Karima Chaoui, Christiane Susini, Marian KochmanAbstract:Juvenile Hormone (JH) controls insect development, metamorphosis and reproduction. In insect hemolymph a significant proportion of JH is bound to juvenile Hormone Binding protein (JHBP), which serves as a carrier supplying the Hormone to the target tissues. To shed some light on JHBP passage within insect tissues, the interaction of this carrier with other proteins from Galleria mellonella (Lepidoptera) was investigated. Our studies revealed the presence of JHBP within the tracheal epithelium and fat body cells in both the membrane and cytoplasmic sections. We found that the interaction between JHBP and membrane proteins occurs with saturation kinetics and is specific and reversible. ATP synthase was indicated as a JHBP membrane Binding protein based upon SPR-BIA and MS analysis. It was found that in G. mellonella fat body, this enzyme is present in mitochondrial fraction, plasma membranes and cytosol as well. In the model system containing bovine F(1) ATP synthase and JHBP, the interaction between these two components occurs with K(d)=0.86 nM. In hemolymph we detected JHBP Binding to apolipophorin, arylphorin and hexamerin. These results provide the first demonstration of the physical interaction of JHBP with membrane and hemolymph proteins which can be involved in JHBP molecule traffic.
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insect juvenile Hormone Binding protein shows ancestral fold present in human lipid Binding proteins
Journal of Molecular Biology, 2008Co-Authors: Robert Kolodziejczyk, G Bujacz, Michal Jakob, Andrzej Ozyhar, Mariusz Jaskolski, Marian KochmanAbstract:Low molecular weight juvenile Hormone Binding proteins (JHBPs) are specific carriers of juvenile Hormone (JH) in the hemolymph of butterflies and moths. As hormonal signal transmitters, these proteins exert a profound effect on insect development. The crystal structure of JHBP from Galleria mellonella shows an unusual fold consisting of a long α-helix wrapped in a highly curved antiparallel β-sheet. JHBP structurally resembles the folding pattern found in tandem repeats in some mammalian lipid-Binding proteins, with similar organization of one cavity and a disulfide bond between the long helix and the β-sheet. JHBP reveals, therefore, an archetypal fold used by nature for hydrophobic ligand Binding. The JHBP molecule possesses two hydrophobic cavities. Several lines of experimental evidence conclusively indicate that JHBP binds JH in only one cavity, close to the N- and C-termini, and that this Binding induces a structural change. The second cavity, located at the opposite end of the molecule, could bind another ligand.
Joann E Manson - One of the best experts on this subject based on the ideXlab platform.
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abstract 73 sex Hormone Binding globulin a novel hormonal biomarker for ischemic stroke risk
Stroke, 2020Co-Authors: Tracy E Madsen, Joann E Manson, Xi Luo, Mengna Huang, Ki Park, Marcia L Stefanick, Simin LiuAbstract:Introduction: Sex Hormone Binding globulin (SHBG) is a sex-steroid transporter previously linked to cardiometabolic outcomes such as diabetes (DM) and coronary heart disease and their risk factors....
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circulating shbg sex Hormone Binding globulin and risk of ischemic stroke findings from the whi
Stroke, 2020Co-Authors: Tracy E Madsen, Mengna Huang, Ki Park, Marcia L Stefanick, Joann E MansonAbstract:Background and Purpose— Circulating levels of SHBG (sex Hormone-Binding globulin) have been inversely linked to obesity, diabetes mellitus, and other cardiometabolic disorders. It remains uncertain...
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abstract p047 circulating testosterone and sex Hormone Binding globulin concentrations and risk of type 2 diabetes cardiovascular disease and all cause mortality in us women
Circulation, 2019Co-Authors: Tianyi Huang, Joann E Manson, Kathryn M Rexrode, Susan E Hankinson, Shelley S TworogerAbstract:Introduction: It remains unclear whether circulating testosterone and sex Hormone-Binding globulin (SHBG) are associated with cardiometabolic disease risk and mortality. Hypothesis: Higher SHBG and...
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sex Hormone Binding globulin and risk of type 2 diabetes in women and men
The New England Journal of Medicine, 2009Co-Authors: Eric L Ding, Yiqing Song, Joann E Manson, David J Hunter, Nader Rifai, Julie E Buring, Michael J GazianoAbstract:Background Circulating sex Hormone–Binding globulin levels are inversely associated with insulin resistance, but whether these levels can predict the risk of developing type 2 diabetes is uncertain. Methods We performed a nested case–control study of postmenopausal women in the Women’s Health Study who were not using Hormone therapy (359 with newly diagnosed type 2 diabetes and 359 controls). Plasma levels of sex Hormone–Binding globulin were measured; two polymorphisms of the gene encoding sex Hormone–Binding globulin, SHBG, that were robustly associated with the protein levels were genotyped and applied in mendelian randomization analyses. We then conducted a replication study in an independent cohort of men from the Physicians’ Health Study II (170 with newly diagnosed type 2 diabetes and 170 controls). Results Among women, higher plasma levels of sex Hormone–Binding globulin were prospectively associated with a lower risk of type 2 diabetes: multivariable odds ratios were 1.00 for the first (lowest) quartile of plasma levels, 0.16 (95% confidence interval [CI], 0.08 to 0.33) for the second quartile, 0.04 (95% CI, 0.01 to 0.12) for the third quartile, and 0.09 (95% CI, 0.03 to 0.21) for the fourth (highest) quartile (P<0.001 for trend). These prospective associations were replicated among men (odds ratio for the highest quartile of plasma levels vs. the lowest quartile, 0.10; 95% CI, 0.03 to 0.36; P<0.001 for trend). As compared with homozygotes of the respective wild-type allele, carriers of a variant allele of the SHBG single-nucleotide polymorphism (SNP) rs6259 had 10% higher sex Hormone–Binding globulin levels (P = 0.005), and carriers of an rs6257 variant had 10% lower plasma levels (P = 0.004); variants of both SNPs were also associated with a risk of type 2 diabetes in directions corresponding to their associated sex Hormone–Binding globulin levels. In mendelian randomization analyses, the predicted odds ratio of type 2 diabetes per standard-deviation increase in the plasma level of sex Hormone–Binding globulin was 0.28 (95% CI, 0.13 to 0.58) among women and 0.29 (95% CI, 0.15 to 0.58) among men, a finding that suggests that sex Hormone–Binding globulin may have a causal role in the risk of type 2 diabetes. Conclusions Low circulating levels of sex Hormone–Binding globulin are a strong predictor of the risk of type 2 diabetes in women and men. The clinical usefulness of both SHBG genotypes and plasma levels in stratification and intervention for the risk of type 2 diabetes warrants further examination.
R H Mortimer - One of the best experts on this subject based on the ideXlab platform.
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synthesis of thyroid Hormone Binding proteins transthyretin and albumin by human trophoblast
The Journal of Clinical Endocrinology and Metabolism, 2005Co-Authors: Brett Mckinnon, Kerry Richard, R H MortimerAbstract:Context: Mechanisms regulating materno-fetal transfer of thyroid Hormone are not well understood. Modulation of trophoblast type 3 iodothyronine deiodinase (D3) may play an important role. Objective: The objective of this study was to investigate trophoblast thyroid Hormone Binding proteins that may modulate interactions between D3 and T4. Design: Placentas were obtained by informed consent from women delivering normal infants by repeat cesarean section at 38–40 wk gestation. T4 and T3 Binding was examined in human placenta. Serum thyroid Hormone Binding proteins were identified by Western blotting, and their mRNA was examined by RT-PCR. Presence of these proteins in trophoblast was determined by immunocytochemistry and immunofluorescence. Cytosol was progressively purified to reveal additional thyroid Hormone Binding proteins that were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry. Effects of mefenamic acid on placental deiodination were examined by HPLC. Resu...
Eric L Ding - One of the best experts on this subject based on the ideXlab platform.
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the effects of caffeinated and decaffeinated coffee on sex Hormone Binding globulin and endogenous sex Hormone levels a randomized controlled trial
Nutrition Journal, 2012Co-Authors: Nicole M Wedick, Christos S Mantzoros, Eric L Ding, Aoife M Brennan, Bernard Rosner, Eric B RimmAbstract:Background Findings from observational studies suggest that sex Hormone-Binding globulin (SHBG) and endogenous sex Hormones may be mediators of the putative relation between coffee consumption and lower risk of type 2 diabetes. The objective of this study was to evaluate the effects of caffeinated and decaffeinated coffee on SHBG and sex Hormone levels.
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sex Hormone Binding globulin and risk of type 2 diabetes in women and men
The New England Journal of Medicine, 2009Co-Authors: Eric L Ding, Yiqing Song, Joann E Manson, David J Hunter, Nader Rifai, Julie E Buring, Michael J GazianoAbstract:Background Circulating sex Hormone–Binding globulin levels are inversely associated with insulin resistance, but whether these levels can predict the risk of developing type 2 diabetes is uncertain. Methods We performed a nested case–control study of postmenopausal women in the Women’s Health Study who were not using Hormone therapy (359 with newly diagnosed type 2 diabetes and 359 controls). Plasma levels of sex Hormone–Binding globulin were measured; two polymorphisms of the gene encoding sex Hormone–Binding globulin, SHBG, that were robustly associated with the protein levels were genotyped and applied in mendelian randomization analyses. We then conducted a replication study in an independent cohort of men from the Physicians’ Health Study II (170 with newly diagnosed type 2 diabetes and 170 controls). Results Among women, higher plasma levels of sex Hormone–Binding globulin were prospectively associated with a lower risk of type 2 diabetes: multivariable odds ratios were 1.00 for the first (lowest) quartile of plasma levels, 0.16 (95% confidence interval [CI], 0.08 to 0.33) for the second quartile, 0.04 (95% CI, 0.01 to 0.12) for the third quartile, and 0.09 (95% CI, 0.03 to 0.21) for the fourth (highest) quartile (P<0.001 for trend). These prospective associations were replicated among men (odds ratio for the highest quartile of plasma levels vs. the lowest quartile, 0.10; 95% CI, 0.03 to 0.36; P<0.001 for trend). As compared with homozygotes of the respective wild-type allele, carriers of a variant allele of the SHBG single-nucleotide polymorphism (SNP) rs6259 had 10% higher sex Hormone–Binding globulin levels (P = 0.005), and carriers of an rs6257 variant had 10% lower plasma levels (P = 0.004); variants of both SNPs were also associated with a risk of type 2 diabetes in directions corresponding to their associated sex Hormone–Binding globulin levels. In mendelian randomization analyses, the predicted odds ratio of type 2 diabetes per standard-deviation increase in the plasma level of sex Hormone–Binding globulin was 0.28 (95% CI, 0.13 to 0.58) among women and 0.29 (95% CI, 0.15 to 0.58) among men, a finding that suggests that sex Hormone–Binding globulin may have a causal role in the risk of type 2 diabetes. Conclusions Low circulating levels of sex Hormone–Binding globulin are a strong predictor of the risk of type 2 diabetes in women and men. The clinical usefulness of both SHBG genotypes and plasma levels in stratification and intervention for the risk of type 2 diabetes warrants further examination.
