atrial-natriuretic-factor and Polycystic-Ovary-Syndrome

The aim was to investigate the impact of polycystic ovary syndrome (PCOS) on the regulation of lipolysis by catecholamine and for the first time atrial natriuretic peptide (ANP) before and after 16 wk of aerobic training.. Eight hyperandrogenic obese women with PCOS [age, 25 +/- 1 yr; body mass index (BMI), 32.0 +/- 1.6 kg/m(2)] and seven healthy BMI-matched controls participated. Studies were performed before and after a 16-wk exercise training program in women with PCOS and cross-sectionally in a group of BMI-matched controls.. Lipolysis was measured in vitro in isolated adipocytes and in vivo by microdialysis of sc abdominal adipose tissue before and during a hyperinsulinemic euglycemic clamp.. In vitro, baseline and maximal ANP- and isoproterenol-induced lipolysis was markedly reduced in PCOS women. Baseline (P < 0.001) and ANP-(P < 0.01) and isoproterenol-(P < 0.001) mediated lipolysis, however, was remarkably increased after training, independent of changes in body weight and sex hormones. These functional improvements were supported by an increased 1) lipolytic sensitivity for ANP (1.3-fold; P < 0.05); 2) lipolytic responsiveness for isoproterenol (1.7-fold; P < 0.01); and 3) postreceptor-acting agent dibutyryl-cAMP (activating cAMP-dependent protein kinase) (2.1-fold; P < 0.05). In vivo, the lipolytic responsiveness to isoproterenol was also reduced in PCOS and tended to increase after exercise training. The insulin suppression of lipolysis during the hyperinsulinemic euglycemic clamp was also reduced in PCOS.. Together, these data show that the regulation of lipolysis by the main endocrine hormones is impaired in women with PCOS. These lipolytic defects can be partly reversed by aerobic exercise training independent of changes in body fat mass and sex hormones.

Topics: Adult; Atrial Natriuretic Factor; Body Mass Index; Catecholamines; Exercise; Exercise Therapy; Female; Glucose Clamp Technique; Humans; Insulin; Isoproterenol; Lipolysis; Microdialysis; Obesity; Polycystic Ovary Syndrome; Young Adult

Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease characterized by polycystic ovaries, hyperandrogenism and anovulation. It is one of the main causes of infertility. RU486 is an antagonist of progesterone receptor, and most commonly used as a contraceptive. However, whether RU486 is correlated with PCOS remains unclear. Atrial natriuretic peptide (ANP) is a small peptide with natriuretic and diuretic functions, and its availability to be used in PCOS treatment is unknown. Here, we showed that the serum ANP level was lower in PCOS patients than that in healthy women, and it was also decreased in the serum and ovarian tissues of RU486-induced PCOS rats compared with the control rats. We also found that RU486 inhibited the proliferation and promoted the apoptosis of human KGN ovarian granulosa cells by downregulating progesterone receptor membrane component 1 (PGRMC1). Meantime, ANP promoted the proliferation and inhibited the apoptosis of KGN cells through upregulating ANP receptor A (NPRA). The promotive effects of ANP on ovarian functions were mediated through the formation of an NPRA/PGRMC1/EGFR complex, which further activated MAPK/ERK signaling and transcription factor AP1. Moreover, ANP treatment reversed the PCOS symptoms, and improved the fertility of RU486-induced PCOS rats. Collectively, these findings highlight that RU486 is associated with the pathogenesis of PCOS, and ANP treatment may be a promising therapeutic option for PCOS.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Cell Proliferation; ErbB Receptors; Female; Granulosa Cells; Humans; Membrane Proteins; Mifepristone; Ovary; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley; Receptors, Progesterone; Transfection

Polycystic ovary syndrome (PCOS) defined by the Rotterdam criteria does not take into account the unhealthy metabolic profile of the syndrome with increased insulin resistance (IR) and overweight favoring development of type 2 diabetes, hypertension and cardiovascular disease (CVD). We assess three vasoactive peptides associated with CVD in women with PCOS.. Plasma levels of mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin and mid-regional pro-adrenomedullin (MR-proADM) were measured in 98 PCOS patients and 46 age- and BMI-matched healthy women.. We found no difference in levels of MR-proANP, copeptin and MR-proADM between the PCOS and control group. Multiple regression analyses on a combined group of PCOS and control subjects demonstrated an inverse correlation between MR-proANP and IR (measured by fasting C-peptide) and a positive correlations between copeptin and IR as well as MR-proADM and BMI. We found no association between peptide levels and different Rotterdam phenotypes.. Plasma concentrations of MR-proANP, copeptin and MR-proADM were not increased in PCOS compared to age- and BMI-matched controls. Thus, these peptides cannot be used to detect increased risk of CVD in a young PCOS cohort.

Topics: Adolescent; Adrenomedullin; Adult; Atrial Natriuretic Factor; Case-Control Studies; Female; Glycopeptides; Humans; Polycystic Ovary Syndrome; Young Adult

Atrial natriuretic peptide (ANP) is known to regulate ovarian functions, such as follicular growth and steroid hormone production. The aim of the present study was to investigate the natriuretic peptide system in a rat model of chronic anovulation, the rat polycystic ovary. Adult female Wistar rats received a single subcutaneous injection of 2mg estradiol valerate to induce polycystic ovaries, while the control group received vehicle injection. Two months later, their ovaries were quickly removed and analyzed. Polycystic ovaries exhibited marked elevation of testosterone and estradiol levels compared to control ovaries. The levels of ANP and the expression of ANP mRNA were highly reduced in the polycystic ovaries compared to controls. By immunohistochemistry, polycystic ovaries showed weaker ANP staining in stroma, theca cells and oocytes compared to controls. Polycystic ovaries also had increased activity of neutral endopeptidase, the main proteolytic enzyme that degrades natriuretic peptides. ANP receptor C mRNA was reduced and ANP binding to this receptor was absent in polycystic ovaries. Collectively, these results indicate a downregulation of the natriuretic peptide system in rat polycystic ovary, an established experimental model of anovulation with high ovarian testosterone and estradiol levels. Together with previous evidence demonstrating that ANP inhibits ovarian steroidogenesis, these findings suggest that low ovarian ANP levels may contribute to the abnormal steroid hormone balance in polycystic ovaries.

Topics: Animals; Atrial Natriuretic Factor; Down-Regulation; Estradiol; Female; Injections, Subcutaneous; Polycystic Ovary Syndrome; Rats; Rats, Wistar; RNA, Messenger; Testosterone

It is believed that a dysfunction in adipose tissue plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). Natriuretic peptides are hormones that regulate cardiovascular and body fluid homeostasis and adipose tissue metabolism. Natriuretic peptide levels are reduced in individuals with obesity and diabetes.. This study aimed to investigate whether natriuretic peptide levels are altered in women with PCOS and whether they correlate with adiponectin levels or insulin sensitivity markers.. This was a cross-sectional study at a referral center in a teaching hospital.. We evaluated 40 patients diagnosed with PCOS according to the Rotterdam criteria and 36 control women matched for age and body mass index.. We measured serum adiponectin, plasma atrial natriuretic peptide (ANP), and plasma brain natriuretic peptide using enzyme immunoassays in both groups. We evaluated metabolic markers, such as fasting glucose, insulin, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. In addition, we calculated the homeostasis model assessment for insulin resistance index (HOMA-IR) and the lipid accumulation product (LAP) index and tested the linear correlations between these metabolic indices and the plasma ANP and serum adiponectin concentrations.. ANP and adiponectin were reduced in the PCOS group compared with the control group (P = 0.010 and P = 0.014, respectively). The brain natriuretic peptide concentration did not differ between the two groups (P = 0.883). There was no correlation between ANP and any of the metabolic markers. In the control group, the serum adiponectin level was inversely correlated with BMI (P = 0.011), waist circumference (P = 0.021), insulin (P = 0.013), fasting glucose (P = 0.010), homeostasis model assessment for insulin resistance index (P = 0.007), and lipid accumulation product (P = 0.022). Remarkably, none of these correlations were observed in the women with PCOS.. Women with PCOS had lower ANP and adiponectin compared with controls matched for age and BMI. Thus, the mechanisms that affect ANP and adiponectin production and clearance may be altered in PCOS, regardless of adiposity. These hormones may be involved in the metabolic features of PCOS.

Topics: Adiponectin; Adiposity; Adult; Atrial Natriuretic Factor; Biomarkers; Body Mass Index; Cross-Sectional Studies; Down-Regulation; Female; Hospitals, Teaching; Humans; Insulin Resistance; Lipid Metabolism; Natriuretic Peptide, Brain; Overweight; Polycystic Ovary Syndrome