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.

Interactions of sex hormone-binding globulin with target cells

2010 ◽  
Vol 316 (1) ◽  
pp. 79-85 ◽  
Author(s):  
William Rosner ◽  
Daniel J. Hryb ◽  
Scott M. Kahn ◽  
Atif M. Nakhla ◽  
Nicholas A. Romas
Keyword(s):  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Target Cells ◽  
Hormone Binding

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 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

Efficient eukaryotic expression system for authentic human sex hormone-binding globulin

2001 ◽  
Vol 360 (3) ◽  
pp. 609-615 ◽  
Author(s):  
Jan HILPERT ◽  
Henrik VORUM ◽  
Regina BURMEISTER ◽  
Robert SPOELGEN ◽  
Irina GRISHKOVSKAYA ◽  
...  
Keyword(s):  
Steroid Hormones ◽  
Plasma Membranes ◽  
Recombinant Expression ◽  
Expression System ◽  
Eukaryotic Expression ◽  
Sex Hormone ◽  
Membrane Receptors ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Glycosylation Pattern

Sex hormone-binding globulin (SHBG) is the main carrier for androgens and oestrogens in humans. It mediates the transport of steroid hormones in the circulation and testicular fluid, and regulates their bioavailability to steroid-responsive tissues. In addition, the protein interacts with membrane receptors expressed in target tissues. Binding to the receptors is suspected to facilitate the uptake of steroid hormones and/or elicit cellular signal transduction. The identity of the SHBG receptor has not yet been resolved, in part due to a lack of sufficient quantities of authentic SHBG for receptor purification and molecular characterization. We have successfully addressed this problem by establishing an episomal expression system in human embryonic kidney cells that produces 5mg of fully active human SHBG per litre. The recombinant protein resembles native SHBG in terms of structure, glycosylation pattern and steroid-binding activity. Moreover, the protein interacts with plasma membranes in steroid target tissues, an activity not observed with SHBG from other recombinant expression systems. Thus our studies have removed an important obstacle to the further elucidation of the role SHBG plays in steroid hormone action.

scholarly journals Sex hormone-binding globulin as a marker for hyperinsulinemia and/or insulin resistance in obese children

2000 ◽  
pp. 85-89 ◽  
Author(s):  
F Gascon ◽  
M Valle ◽  
R Martos ◽  
FJ Ruz ◽  
R Rios ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Sex Hormone ◽  
Obese Group ◽  
Sex Hormone Binding Globulin ◽  
Control Group ◽  
Hormone Binding ◽  
Obese Children ◽  
Anthropometric Measures ◽  
Cross Sectional ◽  
Glucose Ratio

OBJECTIVE: A relationship between hyperinsulinemia and decreased serum sex hormone-binding globulin (SHBG) has been described in adults. We evaluated the usefulness of SHBG as an index of hyperinsulinemia and/or insulin resistance in obese children (aged 6-9 years) of both sexes and its possible influence on the androgenic status. DESIGN: We carried out a cross-sectional study of cases and controls. We studied 61 obese children (22 males, 39 females) with body mass index (BMI) superior to the 90(th) percentile and a control group of age- and sex-matched non-obese children. We measured serum glucose, insulin, TSH, free thyroxine, 17beta-estradiol, testosterone and SHBG. Also, we correlated these parameters with anthropometric measures. RESULTS: The obese group presented significantly elevated levels of insulin (P=0.001) and insulin/glucose ratio (P=0.0012) compared with the control group. SHBG (P=0.0001) and testosterone (P=0.0169) levels were significantly lower than those in the non-obese group. We did not find any difference in the free androgen index (FAI). Fasting insulin (r=-0.4512; P<0.001), BMI (r=-0.3185; P<0.05) and testosterone (r=-0.3705; P<0.01) were inversely correlated with SHBG concentration. According to multivariate analyses, insulin was the only independent predictor factor for serum SHBG concentration in the obese group (r partial=0.1280; P=0.0171). CONCLUSIONS: In summary, at this age there is a strong relationship between insulin and SHBG. The changes in SHBG levels of the obese group did not affect FAI and, therefore, they did not cause changes in the androgenic status. Our data support the role of insulin in the regulation of serum SHBG levels.

scholarly journals The association between sex hormone-binding globulin and type 2 diabetes in Nigerian men

2013 ◽  
Vol 2 (1) ◽  
Author(s):  
Fayefori M. Abbiyesuku ◽  
Augustine N. Agbakwuru ◽  
Olatunbosun O. Olawale
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Sex Hormone ◽  
Diabetic Group ◽  
Sex Hormone Binding Globulin ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hormone Binding ◽  
Male Subjects ◽  
Type 2 Diabetic

Background: Epidemiological studies have shown that sex hormone-binding globulin (SHBG) has a role in glucose homeostasis in both men and women. However, a prospective study on Japanese-American subjects concluded that SHBG was not a significant risk factor in either men or women, suggesting ethnic differences. We were not aware of any evaluation of SHBG in subjects of African ancestry.Objectives: We investigated the association between SHBG and insulin resistance in type 2 diabetic diabetic men in a hospital in Nigeria.Method: Forty-eight male subjects with type 2 diabetes and 20 non-diabetic male subjects were recruited in this cross-sectional hospital-based study by the convenient sampling method.Height and circumferences around the waist and hip were measured to the nearest 0.5 cm and the waist–hip ratio was calculated from this measurement. Weight was measured and body mass index was calculated. Fasting plasma glucose concentration was measured by the glucose oxidase method with a between-run coefficient of variation of 3%. Insulin and SHBG were measured by means of enzyme-linked immunosorbent assay (ELISA).Results: There was a statistically-significant difference between test results for the diabetic and non-diabetic patients. The mean SHBG concentration was higher in the non-diabetic group (42.2 nmol/L) than the diabetic group (30.5 nmol/L). A significant inverse association between insulin resistance and SHBG was observed (r = 0.353, p < 0.015).Conclusion: This study supported earlier observations that a significant inverse correlation exists between SHBG and insulin resistance and provides evidence that the relationship may extend to type 2 diabetic men of African ancestry in Nigeria.

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