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Background: Aldosterone-producing adenoma (APA) is a benign adrenal tumor with autonomous aldosterone production which causes hypertension and excess cardiovascular risk. Protein phosphorylation regulates aldosterone secretion from adrenal cortical cells, but how signaling networks are remodeled in APA remains unknown. Methods: We performed an integrated proteomic and phosphoproteomic profiling of 15 APA and 10 matched nonfunctioning adrenocortical tumors (NFAT) based on the 4-dimensional label-free technique. We further validated our main findings in enlarged APA samples, mice, and adrenocortical cell line. Results: The proteomic and phosphoproteomic profiling of APA and NFAT quantified 5989 proteins and 9011 phosphopeptides. We highlighted differentially expressed and phosphorylated proteins which modulated aldosterone synthesis and secretion from APA. As intracellular calcium is the central signal for aldosterone synthesis, our integrated calcium signaling network implicated wolframin in the control of calcium influx and CYP11B2 (aldosterone synthase) activation in APA (ratio of wolframin expression in APA to NFAT: 6.411, P <0.001). Among 97 APA cases for validation, a higher expression level of wolframin was associated with a higher plasma aldosterone concentration postcaptopril challenge test and a higher systolic blood pressure. In vitro, the secretion of aldosterone was enhanced by wolframin overexpression, while aldosterone secretion in response to potassium or angiotensin II was inhibited by the knockdown of wolframin. Further in vivo and in vitro data demonstrated the wolframin-calcium axis as an important regulator of CYP11B2 expression and aldosterone production. Conclusions: Wolframin is a regulatory protein in aldosterone hypersecretion. Remodeled calcium transportation and mitochondrial function are involved in wolframin-related aldosterone secretion. [ABSTRACT FROM AUTHOR]

Abstract Objective This study aims to evaluate whether serum Bisphenol A (BPA) is a risk factor for hyperuricemia. Methods In this prospective study, a total of 482 participants without hyperuricemia were enrolled at baseline and followed up for 6 years. Clinical characteristics were recorded, and serum levels of uric acid and BPA were measured. Participants were stratified into tertiles according to low, median, and high baseline serum BPA levels. Regression models were used to analyze associations of serum BPA with the change in uric acid and the risk of developing hyperuricemia. Results At baseline, serum concentrations of BPA was 0.51 (0.24–2.37) ng/mL. After 6 years of follow-up, the change in serum uric acid concentration from baseline to the 6-year mark was significantly higher in subjects with higher baseline BPA concentration (0.03 ± 0.19, 0.07 ± 0.21, and 0.11 ± 0.25 mg/dL for low, median, and high tertiles, respectively, P = 0.006). When adjusted for potential confounders, such as age, renal function, and history of diabetes and hypertension, multivariable logistic analyses showed that subjects in the median or high baseline BPA tertiles exhibited a twofold higher risk of 6-year hyperuricemia incidence compared to subjects in the low baseline BPA tertile [odds ratio (OR) = 2.28 (95% CI: 1.05–4.95) for the median tertile; 2.42 (1.07–5.48) for the high tertile, P for Trend = 0.043]. Conclusion In conclusion, serum BPA is an independent risk factor for hyperuricemia. [ABSTRACT FROM AUTHOR]

Background/Aims: Serum cortisol level is elevated in patients with essential hypertension. We aimed at investigating the association of serum cortisol levels with parameters of renal function in essential hypertension. Methods: One hundred and seventy-eight patients with essential hypertension participated in the study. Fasting serum samples were collected at 8:00 am. Renal function was measured as estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration creatinine- cystatin C equation (eGFRcr-cys). Correlation analysis and stepwise regression analysis were used to detect the relationship between cortisol and eGFRcr-cys. The distributions of serum cortisol were split by the tertiles and subjects were stratified into those with low, median and high levels accordingly. Results: Serum cortisol levels were significantly higher in subjects whose eGFRcr-cys<90 ml/ min/1.73 m² than subjects whose eGFRcr-cys>90 ml/min/1.73 m² (394.0±93.4 vs. 343.2±98.4 nmol/L, P=0.001). Age, systolic blood pressure, and serum total cholesterol, uric acid, cortisol levels were significantly associated with eGFRcr-cys, serum levels of creatinine and cystatin C. After adjusting for clinical factors, serum cortisol level had a statistically significant negative association with the eGFRcr-cys (α=-0.19, P=0.027), and positive associations with cystatin C (α=0.31, P=0.001) and creatinine (α=0.14, P=0.044). With the increment of cortisol tertile, the eGFRcr-cys significantly decreased (93.18±14.36 vs. 84.61±14.67 vs. 81.29±12.36 ml/min/1.73 m2 for low, median and high tertile, respecively, P=0.001). Conclusion: Serum cortisol level was negatively correlated with eGFRcr-cys in subjects with essential hypertension. Further studies are needed to investigate whether cortisol plays a role in hypertensive nephropathy development. [ABSTRACT FROM AUTHOR]

Introduction: Lipopolysaccharide-binding protein (LBP) is closely associated with many metabolic disorders. However, no study has been done to explore the relationship between LBP and polycystic ovary syndrome (PCOS). The objective of this study was to investigate whether the serum LBP level is elevated and associated with insulin resistance (IR) in PCOS. Participants and Design: In this cross-sectional study, 117 PCOS patients and 121 age-matched controls were recruited. Hyperinsulinemic-euglycemic clamp was performed with an expression of M value for insulin sensitivity. Fasting serum samples were collected to detect LBP, lipids, insulin, sex hormones and high sensitive C reactive protein (hs-CRP). Pearson’s correlation and multiple linear regression was used to analyze the associations between M value and LBP level. Settings: The study was performed in a clinical research center. Results: Compared with controls, PCOS subjects had a significantly higher LBP concentration (33.03±14.59 vs. 24.35±10.31 μg/ml, p<0.001), and lower M value (8.21±3.06 vs. 12.31±1.72 mg/min/kg, p<0.001). Both in lean and overweight/obese individuals, serum LBP level was higher in PCOS subjects than that in controls. M value was negatively correlated with body mass index (BMI), fasting serum insulin, triglycerides, low-density lipoprotein cholesterol (LDL-c), free testosterone, high sensitive C reactive protein (hs-CRP) and LBP, whereas positively correlated with high-density lipoprotein cholesterol (HDL-c) and sex hormone binding globulin (SHBG). Serum LBP level was associated with M value after adjusting for BMI, fasting serum insulin, SHBG, as well as hs-CRP. Conclusion: Serum LBP level significantly is elevated in PCOS, and is independently associated with IR in PCOS. [ABSTRACT FROM AUTHOR]