scholarly journals Sex Hormone-Binding Globulin Gene Expression and Insulin Resistance

2014 ◽  
Vol 99 (12) ◽  
pp. E2780-E2788 ◽  
Author(s):  
Stephen J. Winters ◽  
Jyothi Gogineni ◽  
Marjan Karegar ◽  
Charles Scoggins ◽  
Chris A. Wunderlich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Transcription Factor ◽  
Outcome Measures ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Strong Positive Correlation ◽  
Model Assessment ◽  
Nutritional Regulation ◽  
Hormone Binding

Context: The plasma level of sex hormone binding globulin (SHBG), a glycoprotein produced by hepatocytes, is subject to genetic, hormonal, metabolic, and nutritional regulation, and is a marker for the development of the metabolic syndrome and diabetes. Objective: Because the mechanism for these associations is unclear, and no studies of SHBG gene expression in humans have been published, SHBG mRNA was measured in human liver samples and related to anthropometric data. Setting: Inpatients at a private, nonprofit, university-associated hospital were studied. Participants: Subjects were fifty five adult men and women undergoing hepatic resection as treatment for cancer. Main Outcome Measures: Main outcome measures were SHBG mRNA and serum SHBG levels. Results: SHBG mRNA was a strong predictor of serum SHBG with higher levels of the mRNA and protein in women than in men. The relationship between SHBG mRNA and circulating SHBG differed in males and females consistent with a sex difference in post-transcriptional regulation. A strong positive correlation was found between the level of the mRNA for the transcription factor HNF4α and SHBG mRNA. Insulin resistance (IR), assessed by homeostatis model assessment, was related inversely to SHBG mRNA and to HNF4α mRNA as well as to circulating SHBG levels. These mRNAs, as well as serum SHBG, were higher when the hepatic triglyceride concentration was low, and decreased with increasing body mass index but were unrelated to age. Conclusions: Fat accumulation in liver and IR are important determinants of SHBG gene expression and thereby circulating SHBG levels that are perhaps mediated through effects on the transcription factor HNF4α. These findings provide a potential mechanism to explain why low SHBG predicts the development of type 2 diabetes.

scholarly journals Does sex hormone-binding globulin cause insulin resistance during pubertal growth?

2019 ◽  
Vol 8 (5) ◽  
pp. 510-517 ◽  
Author(s):  
Shenglong Le ◽  
Leiting Xu ◽  
Moritz Schumann ◽  
Na Wu ◽  
Timo Törmäkangas ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Early Adulthood ◽  
Sex Hormone ◽  
Path Model ◽  
Sex Hormone Binding Globulin ◽  
Whole Body ◽  
Model Assessment ◽  
Hormone Binding ◽  
Early Puberty ◽  
Pubertal Growth

Background The directional influences between serum sex hormone-binding globulin (SHBG), adiposity and insulin resistance during pubertal growth remain unclear. The aim of this study was to investigate bidirectional associations between SHBG and insulin resistance (HOMA-IR) and adiposity from childhood to early adulthood. Methods Participants were 396 healthy girls measured at baseline (age 11.2 years) and at 1, 2, 4 and 7.5 years. Serum concentrations of estradiol, testosterone and SHBG were determined by ELISA, glucose and insulin by enzymatic photometry, insulin-like growth factor 1 (IGF-1) by time-resolved fluoroimmunoassays, whole-body fat mass by dual-energy X-ray absorptiometry and HOMA-IR were determined by homeostatic model assessment. The associations were examined using cross-lagged path models. Results In a cross-lagged path model, SHBG predicted HOMA-IR before menarche β = −0.320 (95% CI: −0.552 to −0.089), P = 0.007, independent of adiposity and IGF-1. After menarche, no directional effect was found between SHBG and insulin resistance or adiposity. Conclusions Our results suggest that in early puberty, decline in SHBG predicts development of insulin resistance, independent of adiposity. However, after menarche, no directional influences between SHBG, adiposity and insulin resistance were found, suggesting that observational associations between SHBG, adiposity and insulin resistance in pubertal children may be subject to confounding. Further research is needed to understand the underlying mechanisms of the associations between SHBG and cardiometabolic risk markers in peripubertal children.

scholarly journals Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome

2007 ◽  
Vol 157 (4) ◽  
pp. 499-507 ◽  
Author(s):  
Natia Kajaia ◽  
Helge Binder ◽  
Ralf Dittrich ◽  
Patricia G Oppelt ◽  
Bianca Flor ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Predictive Marker ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Hormone Binding

Background: The aim of the present study is to assess insulin resistance (IR) in women with hyperandrogenic syndrome, which was suggested to replace the term polycystic ovary syndrome by the Androgen Excess Society, and to evaluate whether sex hormone-binding globulin (SHBG) can be used as a predictive marker of IR in hyperandrogenic women. Methods: Clinical, metabolic, and endocrine parameters were measured, and an oral glucose tolerance test was carried out. The women were classified as IR group or non-IR group, in accordance with defined cutoff points for the homeostatic model assessment of IR (HOMA-IR) at ≥2.5, the quantitative insulin sensitivity check index at ≤ 0.33, and the Matsuda insulin sensitivity index (ISI) at ≤ 5. Results: The women classified as having IR had a significantly higher body mass index (BMI) and free androgen index (FAI) and showed significantly lower SHBG and high-density lipoprotein (HDL) levels, regardless of the indices used. However, with the Matsuda ISI, generally more women were diagnosed as having IR, and this group had significantly higher total testosterone and triglyceride values, as well as a higher incidence of hirsutism. Conclusions: Women who were classified as being insulin resistant using insulin sensitivity indices showed significantly higher BMI and FAI values and lower SHBG and HDL levels. However, the Matsuda ISI may be more favorable for identifying IR in hyperandrogenic women. SHBG may serve as a predictive marker of IR in these women, particularly in those who are obese.

Evidence that human placenta is a site of sex hormone-binding globulin gene expression

1993 ◽  
Vol 46 (4) ◽  
pp. 497-505 ◽  
Author(s):  
Fernando Larrea ◽  
Lorenza Díaz ◽  
Cecilia Cariño ◽  
Jorge Larriva-Sahdd ◽  
Laura Carrillo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Placenta ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
A Site ◽  
Globulin Gene

scholarly journals Sex hormone binding globulin and insulin resistance

2013 ◽  
Vol 78 (3) ◽  
pp. 321-329 ◽  
Author(s):  
Ian R. Wallace ◽  
Michelle C. McKinley ◽  
Patrick M. Bell ◽  
Steven J. Hunter
Keyword(s):  
Insulin Resistance ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding

scholarly journals Classic and Novel Sex Hormone Binding Globulin Effects on the Cardiovascular System in Men

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Carla Basualto-Alarcón ◽  
Paola Llanos ◽  
Gerardo García-Rivas ◽  
Mayarling Francisca Troncoso ◽  
Daniel Lagos ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Sex Hormone ◽  
Membrane Receptors ◽  
Sex Hormone Binding Globulin ◽  
Target Cells ◽  
Peroxisome Proliferator ◽  
Hormone Binding ◽  
Peroxisome Proliferator Activated Receptor ◽  
Plasma Membrane Receptors ◽  
Local Expression

In men, 70% of circulating testosterone binds with high affinity to plasma sex hormone binding globulin (SHBG), which determines its bioavailability in their target cells. In recent years, a growing body of evidence has shown that circulating SHBG not only is a passive carrier for steroid hormones but also actively regulates testosterone signaling through putative plasma membrane receptors and by local expression of androgen-binding proteins apparently to reach local elevated testosterone concentrations in specific androgen target tissues. Circulating SHBG levels are influenced by metabolic and hormonal factors, and they are reduced in obesity and insulin resistance, suggesting that SHBG may have a broader clinical utility in assessing the risk for cardiovascular diseases. Importantly, plasma SHBG levels are strongly correlated with testosterone concentrations, and in men, low testosterone levels are associated with an adverse cardiometabolic profile. Although obesity and insulin resistance are associated with an increased incidence of cardiovascular disease, whether they lead to abnormal expression of circulating SHBG or its interaction with androgen signaling remains to be elucidated. SHBG is produced mainly in the liver, but it can also be expressed in several tissues including the brain, fat tissue, and myocardium. Expression of SHBG is controlled by peroxisome proliferator-activated receptor γ (PPARγ) and AMP-activated protein kinase (AMPK). AMPK/PPAR interaction is critical to regulate hepatocyte nuclear factor-4 (HNF4), a prerequisite for SHBG upregulation. In cardiomyocytes, testosterone activates AMPK and PPARs. Therefore, the description of local expression of cardiac SHBG and its circulating levels may shed new light to explain physiological and adverse cardiometabolic roles of androgens in different tissues. According to emerging clinical evidence, here, we will discuss the potential mechanisms with cardioprotective effects and SHBG levels to be used as an early metabolic and cardiovascular biomarker in men.

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