ACTA ENDOCRINOLOGICA (BUC)

Endocrine disruptors (EDs) are considered to have an impact on the function of reproductive axis at different levels as well on reproductive organs in both sexes. Complexity of female reproductive system influenced with various stressors including EDs lead to morphological and functional alterations. This is resulting in modulation of neuroendocrine regulation with consequent developmental irregularities and derangements, causative infertility, endometriosis as well as premature ovarian insufficiency or polycystic ovary syndrome. A number of experimental clues was obtained on female animal models using various EDs such as synthetic estrogens and phytoestrogens, neurotransmitters, pesticides or various chemicals. These substances lead towards consequent derangement of the neuroendocrine control of reproduction from early phases of reproductive development towards different phases of adult reproductive period. This text will address some novel insights into the effects of EDs on neuroendocrine regulation of gonadal axis, effects on ovaries as well on endometrium during implantation period.

Epidemic of obesity is ongoing and did not slow down. Causes of obesity are numerous and very complex. Among them, the concept of bidirectional signaling within the brain-gut-microbiome axis was recently proposed as possible pathophysiological mechanism and become a hot topic in the explanations for the control of food intake. Discoveries of new anti-obesity drugs that are analogs for the receptors for some hormones derived from gastrointestinal tract contribute to the investigations in this area. The human gut microbiota plays a fundamental role in human health and disease and it is considered that it represent an endocrine organ that participate in energy homeostasis and host immunity. Role of gut microbiome has been investigated in metabolic diseases such as obesity, type 2 diabetes and non-alcoholic fatty liver disease. Gut microbiome participate in regulation of various mechanisms inside the gastrointestinal tract due to its production of different bacterial metabolites. In our manuscript we present current knowledge about microbiota in the gut; the relation between gut microbiota and brain; neuroendocrine system and gut-brain axis; immune system and gut-brain axis; endocrine system and gut-brain axis; the role of gut microbiota in obesity development and possible use of gut microbiota for the treatment of obesity.

Context. Cardiovascular risk is increased in women with polycystic ovary syndrome (PCOS). Do insulin sensitizing agents such as metformin (MET) and myoinositol (MI) ameliorate biomarkers of cardiovascular risk? Objective. To compare the effects of MET and MI on blood pressure, lipid profile and high sensitive C-reactive protein (hs-CRP) in women with PCOS in respect to their body mass index (BMI). Design. Open label, parallel randomized, single center study. Subjects and Methods. Sixty six women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of hormones, lipid profile, oxidized LDL (ox-LDL), hs-CRP, blood pressure measurement and clinical assessment of BMI, waist circumference (WC) and Ferriman Gallwey score (FG score) were performed before and after treatment. Results. Thirty patients in each group completed the trial. Compared with MET, MI significantly decreased diastolic blood pressure (DBP) (p=0.036) and significantly increased serum hs-CRP (p=0.043). No differences between groups in total cholesterol (TC), HDL-cholesterol, LDLcholesterol, ox-LDL and triglycerides were reported after 6 months. Treatment with MI reduced BMI (p=0.037), WC (p=0.005), DBP (p=0.021) and TC (p=0.008). During MET treatment a significant decrease in BMI (p=0.005), WC (p=0.004), FG score (p=0.001), testosterone (p=0.013) and free androgen index (FAI) (p=0.006) was observed. Conclusions. Our study showed an advantage of MI in reduction of DBP and TC thus predicting favorable metabolic and cardiovascular outcomes in PCOS women. MET more effectively decrease indices of hyperandrogenism.

Context. There are evidences that excessive production of reactive oxygen species is one of important abnormalities that contribute to development of chronic diabetic complications. Objective. To test the effect of intensive insulin therapy with analogues through the examining the level of oxidative stress parameters. Subjects and Methods. Comparison of data obtained by prospective analysis in 49 patients with T1DM was used, before and after six months of intensive insulin analog therapy. Results. The values of all three investigated parameters of oxidative stress malondialdehyde (MDA); xanthine oxidase (XO) and nitrates and nitrites (NOx) in our population with T1DM compared to the control (group of 42 voluntary blood donors) are statistically higher. The levels of antioxidant protection parameters compared to the control group also differ; the activities of catalase and glutathione peroxidase (GPx) are statistically higher in our population of T1DM patients compared to the control and superoxide dismutase (SOD) activities are statistically lower. The values of all three examined parameters of oxidative stress decrease after six months of intensive insulin analog therapy and were statistically lower after the therapy: for MDA p<0.001, for XO p<0.01 and for NOx p<0.05. The activities of catalase (p<0.001) and GPx (p<0.01) both decrease with therapy, while the activity of SOD is highest after the sixth month of therapy (p<0.001). Conclusion. In our patients with T1DM compared to the control the level of oxidative stress is significantly higher. Intensive insulin analog therapy with aspart and glargine promotes predominantly the improvement of oxidative stress, and in a less degree antioxidant protection.

Context. Prognostic considerations include assessing the risk of liver fibrosis in people with nonalcoholic fatty liver disease (NAFLD). Objectives. This study evaluates the use of hematologic and metabolic parameters regarding liver steatosis and fibrosis scores (FLI and Fib-4) in non-obese type 2 diabetes mellitus (t2DM) patients with NAFLD. Methods. Subjects underwent abdominal ultrasound examinations, and FLI and Fib-4 scores were calculated to evaluate liver steatosis and the risk of liver fibrosis non-invasively: 61 non-obese NAFLD subjects with t2DM were included in the cohort study and were divided into 2 groups depending on the t2DM treatment regimen. Results. Fib-4 and WBC count demonstrated a significant inverse correlation (OR = 0.509, p = 0.007). WBC count had an R2 of 0.237, indicating that this marker could account for up to 23.7% of a variation in Fib-4. Fib- 4 and FFA had positive correlation which did not achieve statistically significant prediction (OR=7.122, p=0.062). Additionally, a significant prediction of HbA1c (OR=1.536, p=0.016) and haemoglobin (OR=1.071, p=0.020) for FLI was revealed. Conclusion. HbA1c and other haematological and metabolic parameters, such as haemoglobin and WBC, may be another non-invasive tool for determining whether nonobese NAFLD patients with t2DM are at risk of developing liver steatosis and fibrosis.

Increase in obesity pandemic all over the world consequently leads to the investigation of possible causes. In addition to the traditional explanation using the so-called caloric model, the field of endocrine disruptors (EDs), especially subgroup called obesogens, offered more light on the pathogenetic mechanisms involved. After the Second World War a correlation between an increased production of exogenous pollutants and actual obesity epidemic was suggested. “Obesogen hypothesis” implies that molecules called obesogens inadequately stimulate the development of adipose cells and lipid accumulation in existing adipose cells, as well as change metabolic balance or hormonal control of appetite and satiety, leading to an increase in body fat mass. The list of obesogens includes some industrial chemicals, biocides, pharmaceuticals, pollutants, and smoke. EDs from the group of obesogens may exert their effects by the impairment in the programming development of adipocytes, by an increase in energetic depot in the adipose tissue, and by influencing neuroendocrine control of appetite and satiety. Increased scientific evidence on obesogens and their mechanisms of action may help to prevent obesity and mitigate deleterious effects of the environment on human life and development. New translational studies are needed to explain the possible mechanism proposed.