Sex Hormone-Binding Globulin in Children and Adolescents.
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ABSTRACT:
SUBMITTER: Ayd?n B
PROVIDER: S-EPMC4805039 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
Publications
Sex Hormone-Binding Globulin in Children and Adolescents.
Aydın Banu B Winters Stephen J SJ
Journal of clinical research in pediatric endocrinology 20150118 1
Sex hormone-binding globulin (SHBG) is a circulating glycoprotein that transports testosterone and other steroids in the blood. Interest in SHBG has escalated in recent years because of its inverse association with obesity and insulin resistance, and because many studies have linked lower circulating levels of SHBG to metabolic syndrome, type 2 diabetes, nonalcoholic fatty liver disease, polycystic ovary syndrome, and early puberty. The purpose of this review is to summarize molecular, clinical, ...[more]
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Project description:BackgroundMetals can interfere with hormonal functioning through indirect mechanisms and by binding at the receptor site; thus, they may be associated with hormonal changes. However, there have been few studies on the health impact of metal exposure among children and adolescents. Thus, we aimed to examine the associations of blood lead level (BLL) with estradiol (E2) and sex hormone-binding globulin (SHBG) among children and adolescents aged 8-19 years in the National Health and Nutrition Examination Survey (NHANES) database.MethodsThis was a cohort study of 2188 individuals from the NHANES. BLL was taken as independent variables, E2 and SHBG as dependent variable. We conducted weighted multivariate linear regression models and smooth curve fittings to evaluate the association between them.ResultsThe BLL was significantly positively associated with serum SHBG level in females, especially when the LnBLL quartiles are between Q3 and Q4. There was an inverted U-shaped association between BLL and E2 with the point of inflection at 1.86 μg/L and a U-shaped association between BLL and SHBG with the point of inflection at 1.86 μg/L in female adolescents aged 16-19 years. Meanwhile, In males, there was a positive trend of correlation between BLL and E2 in the 8-11 years, and 16-19 years groups.ConclusionsThis study found an inverted U-shaped association of BLL with E2 and a U-shaped association between BLL and SHBG in female adolescents aged 16-19 years. This indicates that adjusting blood lead exposure to mitigate the effects of lead on growth and development is important for adolescents aged 16-19 years. Controlling the BLL below 1.86 μg/L may minimize the damage to E2.
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Project description: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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Project description:Sex hormone-binding globulin (SHBG) has emerged as one of the multiple genetic and environmental factors that potentially contribute to the pathophysiology of type 2 diabetes mellitus (T2DM). In addition to epidemiologic studies demonstrating a consistent relationship between decreased levels of serum SHBG and incident T2DM, recent genetic studies also reveal that transmission of specific polymorphisms in the SHBG gene influence the risk of T2DM. At the molecular level, the multiple interactions between SHBG and its receptors in various target tissues suggest physiologic roles for SHBG that are more complex than the simple transport of sex hormones in serum. Taken together, these data provide support for an expanded role of SHBG in the pathophysiology of insulin resistance and T2DM.
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Project description:BackgroundSex hormones are recognized to play a significant role in increasing bone mineral density (BMD) and promoting bone maturation during adolescence. The purpose of our study was to use a database with large population data to evaluate the association of BMD with sex hormones (including testosterone and estradiol) and sex hormone-binding globulin (SHBG) in adolescent boys and girls aged 12-19 years.MethodsThe data for our study were taken from the National Health and Nutrition Examination Survey 2013-2016, and we used weighted multiple linear regression models to assess the relationship between testosterone, estradiol, and SHBG and total BMD. We use weighted generalized additive models and smooth curve fitting to discover underlying nonlinear relationships.ResultsA total of 1648 teenagers (853 boys, 795 girls) were selected for the final analysis. In boys, testosterone and estradiol levels were positively associated with total BMD, whereas SHBG levels were negatively associated with total BMD after adjusting for covariates [P < 0.05; 95% confidence interval (CI)]. In addition, there was a point between estradiol and total BMD, after which the positive correlation between estradiol and total BMD was relatively insignificant in boys. In girls, there was a positive association between estradiol and total BMD (P < 0.05; 95% CI), but there was no significant association between the testosterone (β 0.0004; 95% CI -0.0001 to 0.0008) or SHBG (β -0.0001; 95% CI -0.0002 to 0.0001) levels and total BMD. We also found an inverted U-shaped association between testosterone and total BMD with the inflection point at 25.4 ng/dL of testosterone.ConclusionsWe found differences in the association of sex hormones with total BMD in boys and girls. Based on our findings, an appropriate increase in serum testosterone levels may be beneficial for skeletal development in girls because of the inverted U-shaped relationship (with the inflection point at 25.4 ng/dL of testosterone), and a high testosterone level might be detrimental to BMD. Furthermore, keeping estradiol levels below a certain level in boys (24.3 pg/mL) may be considered.
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Project description:BACKGROUND:Sex hormone-binding globulin (SHBG) has been reported to be a risk factor associated with the development of arthritis by previous observational studies more so of three common forms of arthritis: osteoarthritis (OA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). This study aimed to determine whether the concentrations of circulating SHBG are causally associated with the risk of OA, RA, and AS. METHODS:The two-sample Mendelian randomization (MR) approach was used for this study. The inverse-variance-weighted (IVW) method was used for the main analysis. Single-nucleotide polymorphisms (SNPs) associated with SHBG were selected from a large genome-wide association study (GWAS) of 28,837 European individuals. The summary statistics for OA, RA, and AS were extracted from the UK Biobank Resource (n?=?361,141) and a GWAS dataset (n?=?455,221). RESULTS:Positive causal associations were found between circulating SHBG concentrations and OA (effect?=?1.086; 95% CI, 1.009 to 1.168; P?=?0.027) and RA (effect?=?1.003; 95% CI, 1.000 to 1.007; P?=?0.047) in overall analyses. However, there was no evidence of association between SHBG levels and AS. Based on the stratification of skeletal sites, SHBG levels were found to be significantly associated with hip OA (effect?=?1.423; 95% CI, 1.219 to 1.660; P?=?7.753?×?10-6). However, this was not the case with knee OA. CONCLUSIONS:There were positive causal effects of circulating SHBG on the development of OA and RA. Moreover, there was a site-specific association between SHBG and hip OA. Evidently, measurement of SHBG in serum could be valuable in the clinical assessment of arthritis especially in early screening and prevention of OA and RA. However, the mechanisms by which SHBG plays causal roles in the development of arthritis require further investigations.
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Project description:BackgroundSex hormone-binding globulin (SHBG) is a circulating glycoprotein and a regulator of sex hormone levels, which has been shown to influence various traits and diseases. The molecular nature of SHBG makes it a feasible target for preventative or therapeutic interventions. A systematic study of its effects across the human phenome may uncover novel associations.MethodsWe used a Mendelian randomization phenome-wide association study (MR-pheWAS) approach to systematically appraise the potential functions of SHBG while reducing potential biases such as confounding and reverse causation common to the literature. We searched for potential causal effects of SHBG in UK Biobank (N = 334 977) and followed-up our top findings using two-sample MR analyses to evaluate whether estimates may be biased due to horizontal pleiotropy.ResultsResults of the MR-pheWAS across over 21 000 outcome phenotypes identified 12 phenotypes associated with genetically elevated SHBG after Bonferroni correction for multiple testing. Follow-up analysis using two-sample MR indicated the associations of increased natural log SHBG with higher impedance of the arms and whole body, lower pulse rate, lower bone density, higher odds of hip replacement, lower odds of high cholesterol or cholesterol medication use and higher odds of gallbladder removal.ConclusionsOur systematic MR-pheWAS of SHBG, which was comprehensive to the range of phenotypes available in UK Biobank, suggested that higher circulating SHBG affects the body impedance, bone density and cholesterol levels, among others. These phenotypes should be prioritized in future studies aiming to investigate the biological effects of SHBG or develop targets for therapeutic intervention.
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Project description:ObjectiveWe tested the effects of weight loss on serum estradiol, estrone, testosterone, and sex hormone-binding globulin (SHBG) in overweight/obese women 18 months after completing a year-long, 4-arm, randomized-controlled dietary weight loss and/or exercise trial.MethodsFrom 2005 to 2008, 439 overweight/obese, postmenopausal women (BMI >25 kg/m), 50 to 75 years, were randomized to a year-long intervention: diet (reduced calorie, 10% weight loss, N = 118), exercise (225 min/wk moderate-to-vigorous activity, N = 117), combined diet + exercise (N = 117), or control (N = 87). At 12 months, 399 women provided blood; of these, 156 returned at 30 months and gave a blood sample. Hormones and SHBG were measured by immunoassay. Changes were compared using generalized estimating equations, adjusting for confounders.ResultsAt 30 months, participants randomized to the diet + exercise intervention had statistically significant increases in SHBG levels versus controls (P = 0.001). There was no statistically significant change in SHBG in the exercise or diet intervention arms. Hormone levels did not vary by intervention arm from baseline to 30 months. Participants who maintained weight loss at 30 months had statistically significantly greater decreases in free estradiol and free testosterone (Ptrend = 0.02 and Ptrend = 0.04, respectively) and increases in SHBG (Ptrend < 0.0001) versus those who did not have sustained weight loss. Levels of other analytes did not vary by weight loss at 30 months.ConclusionsSustained weight loss results in reductions in free estradiol and testosterone and increases in SHBG 18-month post-intervention.
| S-EPMC6435415 | biostudies-literature