Circulating SCUBE1 levels in women with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is thought to represent an early manifestation of metabolic syndrome, which is associated with cardiovascular disease. Signal peptide-CUB (complement C1r/C1s, Uegf, and Bmp1)-epidermal growth factor domain-containing protein 1 (SCUBE1) is a platelet activation marker that plays important roles in vascular biology and has been closely linked to cardiovascular events. In the present study, we investigated SCUBE1 levels in lean glucose-tolerant women with PCOS and assessed the possible association between SCUBE1 levels and hormonal and metabolic features of women with PCOS. MATERIALS AND METHODS: The study population consisted of 90 lean [body mass index (BMI) <25 kg/m2] women who were diagnosed as having PCOS using the Rotterdam criteria and 100 age- and BMI-matched healthy controls with no clinical or biochemical feature of hyperandrogenism. Glucose tolerance was evaluated in all subjects before recruitment using the 2 h 75 g oral glucose tolerance test, and only those exhibiting normal glucose tolerance were enrolled. Hormonal and metabolic parameters, and serum SCUBE1 levels were evaluated. RESULTS: Circulating SCUBE1 levels were significantly higher in women with PCOS than in controls (5.9±3.9 vs. 4.2±1.4 ng/mL, p=0.022). No association between SCUBE1 level and clinical or biochemical parameters was found in the control or PCOS group. CONCLUSION: SCUBE1 levels are elevated in women with PCOS compared with those in healthy controls; thus, this protein may be an early biomarker of cardiovascular disease later in life.

Assessment of circulating betatrophin concentrations in lean glucose-tolerant women with polycystic ovary syndrome.

The aims of the current study were to investigate the betatrophin levels in lean glucose-tolerant women with polycystic ovary syndrome (PCOS), and to explore the relationships between these levels and antropometric, hormonal and metabolic parameters. The study population consisted of 50 lean (body mass index [BMI] < 25 kg/m2) women diagnosed with PCOS using the Rotterdam criteria, and 60 age- and BMI-matched healthy controls without any features of clinical or biochemical hyperandrogenism. Before recruitment, glucose tolerance was evaluated in all of the subjects using the 2-h 75 g oral glucose-tolerance test, and only those exhibiting normal glucose tolerance were enrolled. Serum betatrophin levels were significantly higher in women with PCOS (median 322.3; range 44.7-1989.3 ng/L) compared to the controls (median 199.9; range 6.2-1912.9 ng/L; p = .005). In the control group, no significant correlation was evident between betatrophin levels and clinical or biochemical parameters. In the PCOS group, betatrophin levels were positively correlated with prolactin levels (r = .286, p = .046) and negatively correlated with BMI (r = -.283, p = .049), waist/hip ratio (r = -.324, p = .023), and low-density lipoprotein cholesterol levels (r = -.385, p = .006). Impact statement What is already known on this subject: Several studies have suggested that primary alteration in beta-cell function is a pathophysiological feature of PCOS, and insulin resistance is the most significant predictor of beta-cell dysfunction independent of obesity. Betatrophin is a circulating protein that is primarily expressed in the liver in humans. Early experimental investigations demonstrated that overexpression of betatrophin significantly promoted pancreatic beta-cell proliferation, insulin production and improved glucose tolerance. Few studies have investigated the association between PCOS and betatrophin. However, in contrast to our study, the authors included overweight/obese patients and glucose tolerance was not evaluated before recruitment. What the results of this study add: Our results showed that serum betatrophin levels were significantly higher in lean glucose-tolerant PCOS women than in age- and BMI-matched healthy controls. What are the implications of these findings for clinical practice and/or further research: Elevated betatrophin levels in PCOS women, in the absence of obesity and glucose intolerance, may reflect a compensatory mechanism in order to counteract metabolic syndrome-related risk factors.

Immunohistochemical Analysis of E-Cadherin, p53 and Inhibin-α Expression in Hydatidiform Mole and Hydropic Abortion.

The purpose of this study was to investigate the role of E-cadherin, p53, and inhibin-α immunostaining in the differential diagnosis of hydropic abortion (HA), partial hydatidiform mole (PHM), and complete hydatidiform mole (CHM). E-cadherin, p53, and inhibin-α protein expression patterns were investigated immunohistochemically using paraffin -embedded tissue sections from histologically diagnosed cases of HA (n = 23), PHM (n = 24), and CHM (n = 23). Expression patterns of these markers were scored semi-quantitatively according to the staining intensity, percentage of positive cells, and immunoreactivity score. Classification of cases was established on histologic criteria and supported by the molecular genotyping. Immunostaining allowed the identification of specific cell types with E-cadherin, p53, and inhibin-α expression in all cases. E-cadherin expression was detected on the cell surface of villous cytotrophoblasts. We observed a marked decline in the expression of E-cadherin from HAs to PHMs to CHMs. The p53-positive reaction was restricted to the nucleus of villous cytotrophoblasts. Significantly increased p53 expression was observed in CHMs, compared with HAs and PHMs. The expression of inhibin-α was localised in the cytoplasm of villous syncytiotrophoblasts, and the expression of this marker was significantly higher in PHMs and CHMs than HAs. In conclusion, immunohistochemical analysis of E-cadherin, p53, and inhibin-α expression could serve as a useful adjunct to conventional methods in the differential diagnosis of HA, PHM, and CHM.

Evaluation of circulating betatrophin levels in gestational diabetes mellitus.

Experimental data indicate that betatrophin plays a significant role in the regulation of lipid metabolism and glucose homeostasis. In recent years, considerable attention has focused on the relationship between betatrophin and diabetes mellitus in humans. This case-control study included 45 women diagnosed with gestational diabetes mellitus (GDM) and 45 pregnant healthy controls. The groups were matched for maternal and gestational age and body mass index. Serum betatrophin levels were significantly higher in women with GDM (median = 635.8 ng/L; range: 290-1841.6 ng/L) compared to control subjects (median = 320.1 ng/L; range: 94.6-936.8 ng/L; p = 0.001). No significant correlations were observed between serum betatrophin levels and clinical or biochemical parameters in the control group. However, in the GDM group, serum betatrophin levels were positively correlated with weight gain during pregnancy (r = 0.304, p = 0.042), systolic blood pressure (r = 0.394, p = 0.007), fasting insulin level (r = 0.348, p = 0.019), and homeostatic model assessment insulin resistance (HOMA-IR; r = 0.311, p = 0.038). Multivariate stepwise linear regression analysis revealed that fasting insulin levels (ß = 0.342, p = 0.022) and HOMA-IR (ß = 0.312, p = 0.037) were independently associated with serum betatrophin levels.