Research progress on sex hormone-binding globulin involved in the occurrence and development of diabetes mellitus / 中国基层医药

Sex hormone-binding globulin (SHBG) is significantly associated with abnormal glucose metabolism. Low SHBG level is a risk factor for insulin resistance and the occurence of diabetes mellitus. SHBG is negatively correlated with the risk of type 2 diabetes mellitus and plays an important role in regulating insulin resistance while predicting its development. The genotype of SHBG has been found to be closely related to the occurrence of diabetes mellitus. Fatty liver and DNA methylation are also important factors mediating the relationship between SHBG and type 2 diabetes mellitus. The change in SHBG level may be related to insulin resistance by influencing hepatocyte nuclear factor 4a and regulating glucose transporter.

Effects of aging and the body mass index on male sex hormones: a cross-sectional study in 701 Brazilian men / Efeitos do envelhecimento e do índice de massa corporal sobre os hormônios sexuais masculinos: um estudo transversal em 701 homens brasileiros

Background: Some studies indicated that body mass index (BMI) is inversely proportional to serum testosterone concentrations in men. Purposes: This study aimed to analyze the effects of aging and obesity on total testosterone (TT), free testosterone (FT), bioavailable testosterone (BT), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) levels. Methods: A cross-sectional study was performed to assess the clinical and laboratory profiles of 701 patients treated at a private urology clinic in Ponta Grossa, Brazil, from January 2016 to December 2018. Results: Patients' age ranged from 16 to 88 years (mean, 56.9 ± 13.62 years). Age did not significantly influence serum TT concentrations, except compared to patients aged >70 years. However, changes were observed in FT and BT (p < 0.05). The mean SHBG increased with age (p < 0.05). A tendency toward LH elevation was observed in older patients, but it was not statistically significant. An inverse proportional relationship between TT, FT, and BT and the testosterone deficiency rate (TT < 300 ng/dL) was observed within BMI groups (p < 0.05). The testosterone deficiency rate was 21.5% in individuals with normal BMI, 29% in overweight individuals, and 37% in obese individuals. Conclusions: Aging affected the testosterone concentrations in men and became increasingly evident using FT and BT instead of TT. SHBG increased with age. Obesity was associated with a decrease in TT, FT, and BT but also increased the rate of hypogonadism. (AU)

Fundamentos: Alguns estudos indicam que o índice de massa corporal (IMC) é inversamente proporcional à con-centração de testosterona sérica em homens. Objetivos: O objetivo deste estudo é analisar o efeito do envelhe-cimento e da obesidade na testosterona biodisponível total e livre, bem como nos níveis de hormônio luteinizante e globulina ligadora de hormônio sexual. Métodos: Foi realizado um estudo transversal abordando o perfil clínico e laboratorial de 701 pacientes atendidos em uma clínica privada de urologia em Ponta Grossa, Brasil, de janei-ro de 2016 a dezembro de 2018. Resultados: A idade dos pacientes variou de 16 a 88 anos (média de 56,9 ± 13,62 anos). A idade não influenciou significativamente as concentrações séricas de testosterona total, exceto quando comparada a pacientes com mais de 70 anos. No entanto, foi observada diferença na testosterona livre e biodisponível (p <0,05). A média de globulina de ligação aos hormônios sexuais aumentou com a idade (p <0,05). Embora uma tendência à elevação da luteinização tenha sido observada em pacientes mais idosos, ela não foi significativa. Relação inversa entre testosterona total, livre e biodisponível e taxa de deficiência de testosterona (testosterona total <300 ng / dL) foi observada dentro dos grupos de índice de massa corporal (p <0,05). A taxa de deficiência de testosterona em indivíduos com índice de massa corporal normal foi de 21,5%, indivíduos com sobre-peso foi de 29% e em indivíduos com obesidade foi de 37%. Conclusões: O envelhecimento afetou a concentração de testosterona em homens, mais evidente ao avaliar testosterona livre e biodisponível em vez de testosterona total. A globulina de ligação aos hormônios sexuais aumentou com a idade. A obesidade foi associada à redução da testosterona total, livre e biodisponível e ao aumento da taxa de hipogonadismo. (AU)

Association between serum sex hormone-binding globulin and non-alcoholic steatohepatitis / 中华内科杂志

Objective:To investigate the association between serum sex hormone-binding globulin (SHBG) and non-alcoholic steatohepatitis (NASH).Methods:In this cross-sectional study, a total of 371 middle-aged and young obese patients who were hospitalized and underwent liver puncture in Nanjing Drum Tower Hospital from January 2016 to April 2021 were included. The population was divided into control group ( n=43) and non-alcoholic fatty liver disease (NAFLD) group ( n=328) based on the non-alcoholic fatty liver disease activity score. Subjects in NAFLD group were further divided into non-alcoholic fatty liver (NAFL) ( n=60), uncertain-NASH ( n=172), and NASH ( n=96). Serum SHBG was tested in patients with NAFLD who were divided into three subgroups according to tertiles. The liver pathological characteristics in different SHBG level subgroups were compared. The risk factors of NASH were analyzed by logistic regression. The prediction model of NASH noninvasive diagnosis was established by forward stepwise regression, and the diagnostic value of non-invasive model for NASH was evaluated by receiver operating characteristic (ROC) curve. Results:The median age in patients were (32±10) years old with a body mass index of (39.16±6.58) kg/m2, including 236 females (63.6%). Serum SHBG level [ M ( Q1, Q3)] in NAFLD group was significantly lower than that in control group [16.90 (11.43, 23.00) vs. (23.45 (15.40, 31.22) mmol/L, P<0.05], and progressively diminished in NAFL, uncertain-NASH and NASH subgroups [(22.24±10.47), (20.57±19.58), (15.80±8.74) mmol; P for trend<0.05]. Compared with the high-leveled SHBG subgroup, the steatosis score (2.09±0.80 vs. 1.51±0.72, P<0.01) and lobular inflammation score (1.10±0.68 vs. 0.85±0.68, P<0.05) were significantly higher in the low-leveled SHBG group. Multivariate logistic regression analysis indicated that lower serum SHBG level was an independent risk factor for NASH ( OR=2.527, 95% CI: 1.296 to 4.928, P<0.05). The area under ROC curve of SHBG combined with aspartate aminotransferase in predicting NASH in NAFLD patients was 0.752 (95% CI: 0.696 to 0.809). Conclusion:Low serum SHBG level is associated with NASH.

Thyroid disorders in patients with abnormal uterine bleeding in tertiary care hospital in Chengalpattu district

Background: A relationship between the thyroid gland and the gonads is suggested by far more frequent occurrence of thyroid disorders in women than in men by clinical appearance of goiter during pregnancy, puberty, and menopause. Aim of this study was to determine the association between menstrual irregularities and thyroid dysfunction. To analyse the pattern of menstrual dysfunction among women with a thyroid disorder.Methods: This cross-sectional study was done in Karpaga Vinayaga Institute of Medical Sciences and Research Center - obstetrics and gynecology OPD. Over 6 months in the year 2019. 100 women who presented with abnormal uterine bleeding with the below exclusion criteria. Detailed history taking with an emphasis on age, parity, infertility, and menstrual disorders. Evaluation by pelvic examination along with the general physical examination of those with menstrual complaints. Routine investigations like Hb, BT, CT, TLC, DLC, platelet count, and ABO-Rh in all. Then all patients were subjected to estimation of serum T3, T4, TSH with early morning samples.Results: Menorrhagia presents in 39.4% of patients in the normal cohort and 63.6% in the thyroid dysfunction cohort. Hypomenorrhea presents in 4% normal cohort and 9.1% thyroid dysfunction cohort. Hypothyroidism presents in 7.27%, subclinical hypothyroidism in 1.81%, and hyperthyroidism in 0.92% of patients. Amenorrhoea presents in 16.2% of patients of the normal cohort and 9.1% of patients of thyroid dysfunction cohort. No statistical significance between amenorrhoea and thyroid dysfunction.32.3% in the normal cohort and 36.4% in thyroid dysfunction cohort had a bulky uterus. No statistical association exists between thyroid dysfunction and uterine size. In a histopathological examination of the endometrium, 49.5% in the normal cohort and 54.5% thyroid dysfunction cohort reported as proliferative endometrium. Amenorrhoea; the significant association between abnormal uterine bleeding and thyroid disorder (10%).Conclusions: The significant association between abnormal uterine bleeding and thyroid disorder (10%). It brings into focus the increased incidence of hypothyroidism among women with menorrhagia.

Role of sex hormone binding globulin as the early predictor for gestational diabetes mellitus

Background:  The aim of this study was to find role of SHBG as an early predictor for gestational diabetes mellitus.Methods: A hospital based prospective/observational/diagnostic and explorative study. The necessary information was collected from the participants through the prepared set of questionnaires. Pregnant women between 11 to 14 weeks of gestation who visited JSS OPD for antenatal checkup satisfying inclusion and exclusion criteria giving informed and written consent for the study were examined clinically. 3ml of venous blood was drawn with aseptic precautions for the estimation of SHBG and adiponectin. OGTT with 75gms glucose first done at 11 to 14weeks and again at 24-28 weeks and 32-36 weeks were done to the same patient to find out whether the patient developed GDM or not. These mothers were followed periodically till delivery. The sensitivity and specificity of SHBG were assessed and compared in patients who developed GDM.Results: 100 cases were selected for the study. About 12 patients were diagnosed as gestational diabetes mellitus in present study by OGCT at 32 weeks to 36 weeks. In present study about 14 patients had low level of SHBG. Low level of SHBG is found to be statistically significant in predicting GDM in first trimester.Conclusions: The combination of SHBG can be used as predictor of GDM in first trimester.

Correlation between sex hormone binding globulin and type 2 diabetes retinopathy / 中国医师杂志

Objective To investigate the relationship between sex hormone binding globulin (SHBG) in serum and diabetic retinopathy (DR) in patients with type 2 diabetic mellitus (T2DM).Methods A total of 160 hospitalized people with T2DM was enrolled into the study.The patients were divided into two groups with or without merged DR.Clinical and laboratorial data were collected, and the correlation was analyzed between sex hormone binding globulin and diabetic retinopathy.Results (1) Compared to the group without DR, patients in T2DM with DR had significant lower SHBG concentration, triglyceride (TG) and total cholesterol (TC) concentration were increased significantly (P ＜ 0.01).(2) The level of SHBG was associated with waist circumference, body weight, fasting blood glucose, and glycosylated hemoglobin (P ＜ 0.05).(3) While the level of SHBG was significantly increased from Quartile 1 to Quartile4, the prevalence of DR was also significantly decreased (A:70％, B:51.2％,C:40.5％, D:29.7％) (P ＜ 0.01).(4) Logistic regressing analysis shows that with the decrease of SHBG level, the increase of triglyceride levels, the risk of DR was significantly increased (SHBG:OR:0.616,95％ CI:0.447-0.850,P ＜ 0.01;TG:OR:1.323,95％ CI:1.025-1.707,P＜0.05).Conclusions With the decrease of SHBG, the prevalence of DR is significantly increased, lower SHBG may be one of the hazards of T2DM patients with DR.

Study on value of HbA1c,GSP,SHBG,TG and FFA for diagnosing gestational diabetes mellitus / 国际检验医学杂志

Objective To investigate the clinical value of glycosylated hemoglobin(HbA1c),glycosylated serum protein(GSP),sex hormone binding globulin(SHBG),three acylglycerol(TG),free fatty acid(FFA)in diagnosing gestational diabetes mellitus(GDM).Methods 103 cases of GDM patients and 98 cases of healthy pregnant women from February 2015 to August 2016 were selected as the GDM group and control group.The positive detection rates and levels of HbA1c,GSP,SHBG,TG and FFA were compared between the two groups.Moreover the diagnostic efficiency of various indicators was analyzed.Results The levels of HbA1c, GSP,TG and FFA in the GDM group were significantly higher than those in the control group,while the SH-BG level was significantly lower than that in the control group,the difference was statistically significant(P<0.05);the positive rates of HbA1c,GSP,SHBG,TG and FFA in the GDM group were significantly higher than those in the control group,the difference was statistically significant(P<0.05);the specificity,sensitivity and positive prediction value of HbA1c,GSP,SHBG,TG and FFA for jointly diagnosing GDM were signifi-cantly higher than those of single indicator,the difference was statistically significant(P<0.05).Conclusion Detecting HbA1c,NGSP,SHBG,TG and FFA is more accurate for jointly diagnosing GDM,has an important diagnostic value,and can serve as the assisted diagnostic indicators.

Testosterone, Sex Hormone-Binding Globulin and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

ABSTRACT Introduction and aim. Endogenous sex hormones are associated with the risk of diabetes and metabolic syndrome. Recent studies suggested the role of these hormones in nonalcoholic fatty liver disease (NAFLD). We conducted a systematic review and meta-analysis of observational studies investigating the association between sex hormones and NAFLD. Material and methods. A comprehensive search of the databases of the MEDLINE and EMBASE was performed from inception through April 2016. The inclusion criterion was the observational studies that assessed the association of serum total testosterone (TT) and sex-hormone binding globulin (SHBG) and NAFLD. We calculated pooled effect estimates of TT and SHBG with 95% confidence intervals (Cl) comparing between subjects with and without NAFLD by using random-effects model. Results. Sixteen trials comprising 13,721 men and 5,840 women met the inclusion criteria. TT levels were lower in men with NAFLD (MD = -2.78 nmol/l, 95%CI -3.40 to -2.15, I2 = 99%) than in those without. Men with higher TT levels had lower odds of NAFLD whereas higher TT levels increased the odds of NAFLD in women. In both sexes, SHBG levels were lower in patients with NAFLD than controls and this inverse association was stronger in women than men and higher SHBG levels were associated with reduced odds of NAFLD. Conclusion. Our meta-analysis demonstrated a sex-dependent association between TT and NAFLD. Lower TT levels are associated with men with NAFLD and inversely associated with women with NAFLD, whereas higher SHBG levels are associated with lower NAFLD odds in both men and women.

Comparative study of sex hormone levels in patients with Alzheimer's disease / 中国基层医药

Objective To study the change and clinical significance of serum sex hormone levels in patients with Alzheimer's disease(AD).Methods The 1:1 case-control study,male AD group in 25 cases,control group in 25 cases,female AD group in 25 cases,25 cases in the control group.The serum sex hormone levels were measured by chemiluminescence immtmoassay in the two groups,and the data were analyzed.Results There was statistically significant difference in estradiol level between female patients and the control group[(40.820 ± 23.249) pmol/L vs.(153.700 ±113.900) pmol/L,t =4.85,P ＜ 0.001].There were statistically significant differences between male patients and the control group,in estradiol[(99.243 ± 34.657) pmol/L vs.(124.t00 ± 38.432) pmool/L],testosterone [(7.904 ±3.944) nmol/L vs.(19.142 ±7.882) nmol/L] levels (t =2.40,6.37,all P ＜0.05).No significant difference was observed in testosterone level in the female groups (P ＞ 0.05).The promoting follicle stimulating hormone and luteinizing hormone,progesterone,prolactin levels between the male group and female group had no statistically significant differences (all P ＞ 0.05).In patients with simple intelligent screening scale (Mini-Mental State Examination,MMSE),the score was significantly correlated with the level of estradiol (r =-0.281,P ＜ 0.05).Conclusion The level of women's estrogen decline is related to factor in the pathogenesis of AD,estradiol,testosterone levels of male decline is related to factor in the pathogenesis of AD.Estradiol level is low,the severity of the disease moreand more heavy.

Establishment and Phenotype Analysis of SHBG Knockout Mouse Model / 中国生物工程杂志

Objective:To generate sex hormone binding globulin(SHBG) conditional knockout mice model.In order to investigate the physiological function of SHBG in vivo and to provide experimental means for the study of the relationship between SHBG and gestational diabetes mellitus.Methods:The mouse genomic DNA sequence of SHBG was verified through bioinformatic analysis.According to the SHBG genomic DNA sequence,the gene targeting and knockout vector were constructed.Transfection of the vectors to ES cells by electroporation was performed according to common protocol.Positive ES cells were screened and identified by PCR.Therefore,the dual selected ES cells were microinjected into blastula,then blastula transplantations into the host mice.The chimeric mice were mated with C57BL/6J mice,and the Flox mice were obtained after screening.The Flox mice were hybridized with EIIA-Cre transgenic mice,and the progeny of the SHBG gene knockout (SHBG-/-) mice were obtained by autocopuation for several times.Results:Several Flox homozygous mice and SHBG gene knockout mice were successfully obtained.Compared with control mice,homozygous mice of SHBG gene knockout were well developed and had reproductive ability.The growth and development of SHBG knockout mice were not significantly different from that of wild type mice.Conclusion:Homozygous mice model of SHBG gene knockout was successfully established,which laid the foundation for further study of the role of SHBG in the gestational diabetes.The SHBG gene knockout mouse model was successfully established and the preliminary phenotypic analysis was performed,which laid the foundation for further study on the role of SHBG in gestational diabetes mellitus.SHBG gene knockout mice were normal in appearance.Due to the limited number of samples and many unknown biological characteristics of gene knockout mice,it needs further study.

Research on the association between sex hormone binding globulin and the risk of developing cardiovascular diseases in community elderly population / 复旦学报（医学版）

Objective To explore the correlation between sex hormone binding globulin (SHBG) and cardiovascular disease (CVD) in community elderly population.Methods In 2014,1916 elderly people (796 males,and 1 120 females) were selected from Baoshan District Friendship Community,Shanghai.We collected basic epidemiological data and fasting venous blood samples to carry out the detection of biomarkers,and then calculated their ten-year Framingham risk score.In this study,obesity,systolic blood pressure,fasting blood glucose,lipid concentration,and high-sensitive C-reactive protein were considered as CVD risk factors;Framingham risk score was considered as a CVD event prediction risk score.We analyzed the correlations of these factors with SHBG.Results SHBG mean values in the population with a history of CVD were lower than those without a history of CVD (P＜0.001).The correlation coefficient between male SHBG and waist circumference,hip circumference,BMI,systolic pressure,cholesterol,triglycerides,high density lipoprotein cholesterol,apolipoprotein A,high sensitive C-reactive protein were-0.312,-0.307,-0.266,-0.113,0.155,-0.277,0.510,0.394 and-0.130,respectively (P＜0.01).The correlation coefficient between female SHBG and waist circumference,hip circumference,BMI,fasting glucose,cholesterol,triglycerides,high density lipoprotein cholesterol,apolipoprotein A,high-sensitive C-reactive protein were-0.236,-0.248,-0.168,-0.183,0.135,-0.264,0.445,0.358 and-0.295,respectively (P＜0.001).The decrease of SHBG level was consistent with the increase of Framingham score (κ =0.062,P＜0.001).Elevated level of SHBG would reduce the risk of CVD in ten years (P＜0.01).Conclusions There was a negative correlation between baseline SHBG level and CVD risk factors,positive correlation between baseline SHBG level and CVD protection factors in community elderly population;lower SHBG level indicated higher risk of developing CVD events.

Regulatory effect of androgen on the expression of SHBG in ovarian granulose cells / 医学研究生学报

Objective The androgen signaling pathway is involved in the regulation of early follicular growth and follicular atresia, and sex hormone binding globulin (SHBG) is an important factor in regulating the level of local ovarian androgen.This study was to investigate the effects of androgen on the expression of SHBG in ovarian granulosa cells.Methods Human ovarian granule cancer cells were cultured with 0 nmol/L dihydrotestosterone (DHT), 500 nmol/L DHT, or 500 nmol/L DHT + 60 μmol/L Flutamide.The expression of SHBG was detected by Western blot and immunofluorescence staining.Hyperandrogenism (HA) was induced in 6 SD rats by subcutaneous injection of dehydroepiandrosterone (DHEA) and another 6 rats were included in the vehicle control group.At 35 days after modeling, all the rats were sacrificed for measurement of the level of SHBG in the blood from the inferior caval vein by ELISA, the expression of SHBG in the ovarian granulosa cells by immunohistochemistry, and expressions of androgen receptor (AR) and SHBG in the liver by Western blot.Results At 24 hours after modeling, the expression of AR was significantly upregulated in the 300, 400, and 500 nmol/L DHT groups as compared with the 0 nmol/L DHT group (1.06±0.02, 1.61±0.11, and 2.38±0.14 vs 1.06±0.03, P<0.05), and so was that of SHBG, increasing in a concentration-dependent manner, most significantly at 500 nmol/L (P<0.01).Both the expressions of AR and SHBG proteins remarkably elevated in the 500 nmol/L DHT group in comparison with the 0 nmol/L DHT group (P<0.01), but markedly downregulated as compared with the 500 nmol/L DHT + 60 μmol/L Flutamide group (P<0.05).Immunofluorescence staining showed that DHT promoted while the addition of Flutamide inhibited the expressions of AR and SHBG.Immunohistochemical staining of the ovarian tissue revealed a high level of SHBG in the HA rats.Compared with the control group, the HA animals exhibited a significantly decreased expression of serum SHBG (4.80±0.35 vs 2.41±0.14, P<0.01) and that in the liver, but a markedly increased level of the AR protein (P<0.05).Conclusion Activation of the androgen signaling pathway by DHT can promote the expression of SHBG in rat ovarian granulosa cells.

Expression and Correlation of Sex Hormone-binding Globulin,Insulin Signal Transduction and Glucose Transporter Proteins in the Gestational Diabetes Mellitus Placental Tissue / 中国医科大学学报

Objective To study the expression of sex hormone-binding globulin(SHBG),insulin signaling pathway and glucose transporter in placenta of pregnant women with gestational diabetes mellitus(GDM),and to explore its role in the pathogenesis of GDM. Methods A total of 10 full-term and non-obese(BMI0.05). Results of linear correlation analysis showed that there were positive correlations between SHBG mRNA and IRS-2 mRNA(P<0.05),SHBG mRNA and PI3K p85α mRNA(P<0.05),and SHBG mRNA and GLUT-4 mRNA(P<0.05). There was also a remarkable positive correlation between IRS-2 mRNA and GLUT-4 mRNA(P<0.01). There existed negative correlations between IRS-1 mRNA and PI3K p85α mRNA(P<0.05),and IRS-1 mRNA and GLUT-3 mRNA(P<0.05). There existed a remarkable positive correlation between IRS-2 mRNA and GLUT-1 mRNA(P<0.01). Conclusion The defective receptors of insulin signaling pathway are present in GDM placental tissue. Decreased expression of SHBG may be involved in the regulation insulin signaling ,leading to a concomitant decrease expression of relevant insulin signaling components in placental tissue ,implying insulin resistance and developing GDM finally.

Inverse Relationship between Hepatic Steatosis and Alanine Aminotransferase with Sex Hormone-Binding Globulin in Men

PURPOSE: Sex hormone-binding globulin (SHBG) is a serum glycoprotein produced predominantly in hepatocytes. As such, the synthesis of SHBG could be associated with liver function and metabolic syndrome. Alanine aminotransferase (ALT) levels could reflect hepatocellular injury and insulin resistance; however, the relationship between hepatic steatosis and ALT with SHBG has not been investigated in humans. The objective of this study was to investigate the associations between SHBG and hepatocyte damage among Korean male patients with hepatic steatosis enrolled in a health examination program. MATERIALS AND METHODS: We performed a retrospective cross-sectional study with 922 participants who underwent routine health examinations. A total of 922 men with or without hepatic steatosis were divided into three groups. We analyzed the risk of lower serum SHBG levels with or without elevated serum ALT levels using odds ratios with 95% confidence intervals (CIs). RESULTS: A significantly increased risk of lower serum SHBG level was observed in the group with hepatic steatosis and ALT elevation (95% CI 1.591–4.681). CONCLUSION: In men with hepatic steatosis, we found that elevated serum ALT levels were associated with lower serum SHBG levels. This finding suggests that subjects with both hepatic steatosis and increased ALT should be considered to have low levels of SHBG.

Current medical management of endocrine-related male infertility / 亚洲男科学杂志(英文版)

Male factor contributes to 50%-60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an abnormal semen analysis, other male factors can be contributory especially if the sample returns normal. Male infertility can be due to identifiable hormonal or anatomical etiologies that may be reversible or irreversible. This manuscript will highlight existing guidelines and our recommendations for hormone evaluation for male infertility and empiric therapies including multivitamins, estrogen receptor modulators (clomiphene), estrogen conversion blockers (anastrozole), and hormone replacement.

Genetic effects on serum testosterone and sex hormone-binding globulin in men: A Korean twin and family study / 亚洲男科学杂志(英文版)

We conducted a community-based cross-sectional study to evaluate the role of genetics in determining the individual difference in total testosterone and sex hormone-binding globulin levels. Study participants comprised 730 Korean men consisting of 142 pairs of monozygotic twins, 191 pairs of siblings, and 259 father-offspring pairs from 270 families who participated in the Healthy Twin study. Serum concentration of total testosterone and sex hormone-binding globulin were measured by chemiluminescence immunoassay, and free testosterone and bioavailable testosterone were calculated using Vermeulen's method. Quantitative genetic analysis based on a variance decomposition model showed that the heritability of total testosterone, free testosterone, bioavailable testosterone, and sex hormone-binding globulin were 0.56, 0.45, 0.44, and 0.69, respectively after accounting for age and body mass index. Proportions of variance explained by age and body mass index varied across different traits, from 8% for total testosterone to 31% for sex hormone-binding globulin. Bivariate analysis showed a high degree of additive genetic correlation (ρG = 0.67) and a moderate degree of individual-specific environmental correlation (ρE = 0.42) between total testosterone and sex hormone-binding globulin. The findings confirmed the important role of genetics in determining the individually different levels of testosterone and sex hormone-binding globulin during adulthood in Korean men as found in non-Asian populations, which may suggest that common biologic control for determining testosterone level directly or indirectly through binding protein are largely shared among different populations.

Clinical features of patients with polycystic ovary syndrome with different SHBG levels / 实用医学杂志

Objective To investigate the role of SHBG in PCOS. Methods Three hundred and ten PCOS patients were divided into the low-SHBG group , the normal-SHBG group , and 95 healthy women were enrolled in the healthy control group. Results (1) In the low SHBG group, the incidences of IR and MS were higher than those in the the normal SHBG group and the healthy control group (P < 0.05); (2) In the low SHBG group, DHEAS was significantly higher than that in the normal SHBG group (P < 0.05); (3) In the low SHBG group, FINS, HOMA-IR, TG, TC/HDL, TG/HDL, LDL/HDL were significantly higher than those in the normal SHBG group and the healthy control group , but HDL was significantly lower than that in the normal SHBG group (P < 0.05); (4) SHBG was positively correlated with HDL, but was negatively correlated with FPG, FINS, HOMA-IR, TG, TC/HDL, TG/HDL, LDL/HDL. Conclusions Uner the low SHBG level, PCOS patients have high levels of DHEAS, and SHBG may be a risk factor for MS, IR and dislipidemia.

Construction of Targeting Vector for Conditional Knockout of Murine Shbg / 中国医科大学学报

Objective To construct the targeting vector for conditional gene knockout of sex hormone?binding globulin(Shbg)in mice. Methods Based on Red/ET,two LoxP were inserted into both sides of extron 4 and extron 7 for conditional gene knockout of murine Shbg. Firstly,the Shbg gene and its upstream,downstream genes obtained from BAC DNA by PCR were cloned into plasmid pBR322?MK,which was named pBR322?MK?AB. The retrieve plasmid(pBR322?Shbg?Re)was obtained by homologous recombination between the plasmid and BAC.Then a great quantity of Neo fragments obtained from PL452 and PL451 were inserted into the targeting vector after another round of Red/ET and then the final targeting vec?tor(pBR322?MK?SHBG?cko)was achieved. Results The correct structures of the targeting vectors such as pBR322?MK?AB,pBR322?Shbg?Re, SHBG?Ln and pBR322?MK?Shbg?cko were confirmed by restriction enzyme digestion and sequencing analysis. Conclusion The targeting vector for conditional knockout of murine SHBG was successfully constructed. The construction of targeting vector paved the way for conditional knockout mouse strain generated by targeted mutation of Shbg.

Impact of androgen level on body adipose tissue content and distribution in middle life women / 中华妇产科杂志

Objective To investigate the relationship between androgen level and body adipose tissue content and distribution via a cross sectional survey in healthy women aged 40 to 60 years. Methods A total of 222 women were divided into 4 groups according menstruation status, i.e. reproductive stage, early perimenopausal stage, late perimenopausal stage and postmenopausal stage. Serum level of dehydroepiandrosterone (DHEA), total testosterone (TT) and sex hormone binding globulin (SHBG) were measured. Free androgen index (FAI) was calculated. Body adipose tissue content and distribution were measured by dual-energy X-ray absorptiometry. Results In women aged 40 to 60 years, DHEA, TT and FAI level of reproductive stage women was (12.3±4.1) nmol/L, (0.56±0.22) nmol/L and 1.15 (quartile:0.71 to 1.85), respectively. DHEA, TT and FAI level of early perimenopausal stage women was (12.0±3.4) nmol/L, (0.56 ± 0.24) nmol/L and 1.37 (quartile: 0.89 to 1.61), respectively. DHEA, TT and FAI level of late perimenopausal stage women was (14.2 ± 4.7) nmol/L, (0.62 ± 0.18) nmol/L and 1.38 (quartile:1.12 to 1.63). DHEA, TT and FAI level of postmenopausal stage women was (11.6±3.5) nmol/L, (0.45±0.22) nmol/L and 0.94 (quartile:0.47 to 1.49). DHEA, TT and FAI level of perimenopausal stage women was comparable with those of reproductive stage women (P>0.05), however, TT and FAI level of postmenopausal women was significantly lower than those of reproductive stage women (P=0.001, 0.014). The total adipose percentage of reproductive stage women, early perimenopausal stage women, late perimenopausal stage women and postmenopausal stage women were (35 ± 6)%, (35 ± 5)%, (37 ± 4)%and (37 ± 5)%. The adipose percentage in“android”area of reproductive stage women, early perimenopausal stage women, late perimenopausal stage women and postmenopausal stage women were (43±5)%, (43±4)%, (47±5)%and (46±5)%. The total adipose percentage was similar in 4 groups (P=0.312). Compared with reproductive stage women, adipose percentage of“android”area increased in late perimenopausal and postmenopausal women (P=0.026). Women with higher FAI level presented higher adipose tissue content and higher percentage of centrally distributed adipose tissue (r=0.28, P=0.003). Conclusions Body adipose tissue tends to distribute centrally from perimenopausal stage. Androgen level is related to body adipose tissue content and distribution, but may not be the main reason of changes of fat distribution in middle life women.

Investigation of the change of adiponectin level with menopause status in middle aged women and its relationship with androgen / 中华妇产科杂志

Objective To investigate the change of adiponectin level with menopause status in women aged 40 to 65, and its relationship with androgen. Methods A cross-sectional study included woman (aged from 40 to 65) who were in hospital for routine check-up at the Sun Yat-sen Memorial Hospital from August to October in 2013. All subjects underwent laboratory examinations of adiponectin, sex hormone binding globulin (SHBG), dehydroepiandrosterone-sulfate (DHEA-S), total testosterone (TT), collected anthropometric measurements and then calculated free androgen index (FAI) and body mass index (BMI). According to their menstrual status, the subjects were divided into 4 groups: premenopausal group with 119 subjects, perimenopausal group with 60 subjects, early postmenopausal group with 62 subjects, late postmenopausal group with 64 subjects. Results (1) Adiponectin levels declined to its lowest level in menopausal transition and gradually becoming higher after menopause, which showed a U-shaped trajectory. When compared adiponectin levels in late postmenopausal group [(13 ± 5) mg/L] with those in perimenopausal [(8 ± 6) mg/L] or early postmenopausal group [(9 ± 6) mg/L], it all showed significantly difference (P<0.05). (2) Both the adiponectin levels were negatively correlated with waistline in the 4 groups (premenopausal group, r=-0.276;perimenopausal group, r=-0.334;early postmenopausal group, r=-0.211;late postmenopausal group, r=-0.218; all P<0.05). Levels of adiponectin were positively correlated with SHBG (r=0.536, P<0.05) and negatively with FAI (r=-0.363, P<0.05) in menopausal transition, while in late postmenopausal group, negatively correlated with level of DHEA-S (r=-0.450, P<0.05). When adjusted for age, BMI and waistline, the above correlations still exist. Conclusions Adiponectin levels declined to its lowest level in menopausal transition and gradually becoming higher after menopause, which showed a U-shaped trajectory during the sequential menopause status transition in middle aged women. Low level of adiponectin in menopausal transition is closely associated with the relative excess androgen occurred during this stage.