ACTA ENDOCRINOLOGICA (BUC)

Objectives. The exact pathogenesis of the endometriosis is not apparent. MicroRNAs (miRNAs/miRs) are non-coding RNAs that regulate gene expression at the posttranscriptional level. MicroRNAs can be used a diagnostic and therapeutic tools in different disorders such as endometriosis. MiR-181 has a function in embryo implantation. The main aim of this study is to evaluate the expression of miR-181 and its relationship with HOXA11 gene expression in ectopic and eutopic endometrium tissues in women with endometriosis. Study design. Thirty-four women participated in this study. Ectopic tissue samples (N=17) were collected via laparoscopic surgery, and eutopic tissue samples (N=17) were obtained from an endometrial biopsy. Endometrial tissue samples without endometriosis were considered the control group. Tissue samples were placed in RNase-free microtube with RNAlater™ Stabilization Solution (Thermo Fisher Scientific) and were kept at -80 ¯C. Quantitative real time-PCR for MiR-181 and HOXA11 genes were performed. Results. MiR-181 expression level increased in eutopic tissue samples compared to the control group. This expression showed a significantly decrease in an ectopic group compared to the eutopic group. It was observed that HOXA11expression decreased remarkably in eutopic group compared to the control group and increased in ectopic group compared to the eutopic group. Conclusion. MiR-181 and HOXA11 are promising strategies in endometriosis disease. Understanding this relation and regulation roles contribute to realizing the etiology of endometriosis.

Context. Insulin resistance has been detected in a majority of patients with polycystic ovary syndrome (PCOS). Elevated neprilysin levels are associated with insulin resistance. Objective. The present study aims to investigate plasma neprilysin and its relationship with endocrine and metabolic characteristics in patients with PCOS. Subjects and Methods. Thirty-five premenopausal PCOS patients and 35 healthy volunteers of similar age were included in the study. Demographic characteristics, biochemical and hormonal findings and also plasma neprilysin levels were determined in these patients and healthy controls. Results. In our study, HOMA-IR values were significantly higher in PCOS patients (3.3 ± 1.8) compared with the controls [(1.6 ± 1), p<0.01]. Plasma neprilysin levels were significantly higher in the PCOS group compared to the control group (1502.1 ± 1641.2 vs. 764.6 ± 562.6 pg/ mL). There was no difference in plasma neprilysin levels when PCOS patients were classified as overweight-obesity (BMI≥25kg/m2) or non-obesity (BMI<25kg/m2). Conclusion. Our findings revealed significantly higher levels for plasma neprilysin and HOMA-IR values in PCOS patients when compared to controls. No significant differences were noted between obese PCOS patients and non-obese PCOS patients in terms of plasma neprilysin levels.

In acromegalic patients growth hormone (GH) excess induces insulin resistance (IR) but whether this is sufficient for pre-diabetes to occur is a matter of debate.\r\nAim. To assess the relative role of IR and insulin secretion in the pre-diabetes of acromegaly.\r\nMethods. 126 patients with acromegaly (79 women, 47 men) were included. Plasma glucose, GH and insulin levels were measured basal and 30, 60 and 120 minutes during a 75 g oral glucose tolerance test (OGTT). Basal and stimulated IR was assessed by homeostasis model assessment (HOMA), insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI) derived from OGTT (OGTTISI) respectively. Basal and stimulated insulin secretion was assessed using HOMA-B% index and insulinogenic index (IGI), respectively. The local Ethic Committee approved the study.\r\nResults. There were 51 subjects with pre-diabetes and 75 subjects with normal glucose tolerance (NGT). Pre-diabetes group had a significantly higher HOMA-IR index (4.8?3.3 vs 2.5?1.6, p<0.001) and nadir GH in OGTT (9.4 (4.3, 22.2) vs. 4.8 (2.2, 14.5) ng/mL, p=0.02) than NGT group. HOMA-IR did not correlate with nadir GH serum level in pre-diabetes group (r =0.22, p=0.12) but correlated significantly in NGT group (r= 0.5, p<0.001). In contrast, the pre-diabetes group had a lower HOMA-B% index than NGT group (165.4?15.7 vs 228.5?29, p<0.001). HOMA-B% did not correlate with nadir GH in both groups. Unadjusted IGI did not differ between the two groups (0.40?0.07 vs. 0.48?0.05, p=0.34) but became statistically significant after adjusting for both basal IR (HOMA-IR) (0.31?0.06 vs. 0.54?0.05, p=0.01) and stimulated IR (OGTTISI) (0.30?0.06 vs. 0.54?0.05, p=0.005). There were no significant differences between pre-diabetes and NGT groups regarding age, duration of acromegaly and sex.\r\nConclusions. Our data suggest that reduced basal and stimulated insulin secretion express the failure of &#946;-cells adaptation to increased GH-induced-insulin resistance and is the pathogenic mechanism of pre-diabetes in acromegaly.

Content. Metabolically healthy obese (MHO) individuals are characterized by absence of metabolic syndrome. The role of autonomic nervous system in metabolic profile of obese subjects has not been sufficiently investigated. Objective. We analyzed heart rate variability (HRV) in MHO and metabolically unhealthy obese (MUO) premenopausal women. Design. In 42 women metabolic profile was defined as MHO and MUO. Subjects and Methods. For metabolic profile Wildman, IDF and HOMA-IR criteria were used. Autonomic nervous system activity was assessed by analysis of heart rate variability. Results. There was no significant difference in HRV between MHO and MUO premenopausal women. In Wildman division, after adjustment for systolic blood pressure, RRNN and LF/HF were statistically different between groups (p=0.0001; p=0.029). In IDF division, adjusting for waist circumference, LF was significantly different between groups (p=0.004). In HOMA division, adjusting for HOMA, groups were different in SDNN (p=0.009), RMSSD (p=0.002), pNN50 (p=0.003), HF(p=0.002) and TP (p=0.005). Conclusions. Autonomic nervous system does not share the leading role in premenopausal women metabolic profile. The differences in HRV between MHO and MUO women depend on the metabolic health criteria. Systolic blood pressure, HOMA and waist circumference have significant effect on HRV differences between MHO and MUO premenopausal women.

Diabetes mellitus is associated with impairment of testicular functions.\r\nAim. The present study aimed to investigate the effects of ethyl pyruvate (EP) on the testicular tissue damage in rats\r\nwith streptozotocin (STZ)-induced diabetes.\r\nSubjects and methods. Thirty-two Wistar albino male rats were assigned into four equal groups as follows: (1) control\r\ngroup (n:8); (2) EP-treated non-diabetic group (n:8); (3) diabetic group (n:8); and (4) EP-treated diabetic group (n:8). Rats with STZ-induced diabetes were kept alive for 14\r\nweeks. After that, the EP solution was administered intraperitoneally to the rats in the EP-treated non-diabetic and diabetic groups at the dose of 50 mg/kg twice daily\r\nfor 14 days. At the end of this period, the left testes were removed from the rats for malondialdehyde (MDA) analysis, and the right testes were removed for histological\r\nexamination.\r\nResults. As compared with the control group, the diabetic group had elevated MDA levels (210.9?12.7) and increased\r\nthickness of the basement membrane of the seminiferous tubules (3.01?0.16), but decreased tubular diameter (159?9.0) and Johnsen?s score (5.31?0.1). In the EPtreated\r\ndiabetic group, diabetes-induced impairment was significantly improved.\r\nConclusion. These findings indicate that EP shows protective effects against diabetes-induced testicular dysfunction.

Background. Recent studies suggested that MPTP could cause gastrointestinal motility deficits additionally to its nonconclusive and controverted effects on the CNS (behavior and brain oxidative stress) in rats. A possible interaction between MPTP typical impairments and magnesium modulatory potential was previously suggested, as magnesium role was described in neuroprotection, gastrointestinal function, and oxidative stress. Aim. To investigate the possible modulatory effect of several magnesium intake formulations (via drinking water) in MPTP neurotoxicity and functional gastrointestinal impairment induction. Materials and Methods. Adult male Wistar rats were subjected to 3-week magnesium intake-controlled diets (magnesium depleted food and magnesium enriched drinking water) previously to acute subcutaneous MPTP treatment (30 mg/ kg body weight). Gastrointestinal motility (one hour stool collection test), and behavioral patterns (Y maze task, elevated plus maze test, open field test, forced swim test) were evaluated. Followingly, brain and bowel samples were collected, and oxidative stress was evaluated (glutathione peroxidase activity, malondial-dehyde concentrations). Results. MPTP could lead to magnesium intakedependent constipation-like gastrointestinal motility impairments, anxiety- and depressive-like affective behavior changes, and mild pain tolerance defects. Also, we found similar brain and intestinal patterns in magnesium-dependent oxidative stress. Conclusion. While the MPTP effects in normal magnesium intake could be regarded as not fully relevant in rat models and limited to the current experimental conditions, the abnormalities observed in the affective behavior, gastrointestinal status, pain tolerance, peripheric and central oxidative status could be indicative of the extent of the systemic effects of MPTP that are not restricted to the CNS level, but also to gastro-intestinal system.

Context. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel biomarker for cardiovascular diseases (CVD) risk estimation with high specificity for vascular inflammation. Few studies have investigated Lp-PLA2 levels in patients with metabolic syndrome (MetS) and obstructive sleep apnea syndrome (OSAS). Objective. This study aimed to evaluate the role of Lp-PLA2 levels as a marker of vascular inflammation that contributes to cardiometabolic dysfunction in patients with MetS and OSAS. Design. This is a prospective case-control study. Subjects and Methods. 83 men were enrolled. Following anthropometric measurements, laboratory analysis and overnight sleep study, patients were divided into three groups: MetS, OSAS with/without MetS. Serum Lp-PLA2 levels were determined by ELISA method. Results. Serum Lp-PLA2 levels were statistically significant among the three groups and were higher in OSAS with MetS group than those without MetS. A significant positive relationship between increased Lp-PLA2 level and CRP (C-reactive protein) and apnea–hypopnea index (AHI) was found. Average oxygen saturation (AvO2) and the lowest oxygen saturation were negatively correlated with Lp-PLA2. The number of desaturation events, oxygen desaturation index, AvO2, AHI and CRP were significant predictors of Lp-PLA2. Conclusions. Lp-PLA2 levels are associated with OSAS severity and might play an important role in predicting CVD in OSAS with/without MetS

Objective. Metabolic syndrome (MetS) is a metabolic condition with high prevalence worldwide. This study aims to examine the relationship between serum concentrations of gastrointestinal hormones such as cholecystokinin (CCK), ghrelin, peptide YY (PYY), and high sensitive C-reactive protein (hs-CRP) and the ingredients of MetS in obese population. Subjects and Methods. This case-control study included 40 obese subjects (20 with MetS and 20 BMI and age-matched control individuals). The age range of the participants was 20-50 years and the participants’ anthropometric characteristics were measured. Serum lipids and the concentrations of oxidized low density lipoprotein (Ox-LDL), insulin, hs-CRP, CCK, PYY, and ghrelin were assessed with commercial ELISA kits. Results. Serum levels of hs-CRP, total cholesterol (TC) and triglycerides (TG) in patients with MetS were significantly higher while CCK and insulin concentrations were higher in obese non- MetS group (P <0.05). PYY had a negative association with waist circumference (WC) and high density lipoprotein cholesterol (HDL-C) and ghrelin had a positive association with systolic blood pressure (SBP) and TC in obese control group (P < 0.05). In obese patients with MetS, hs-CRP had a strong positive association with TG. Conclusion. The current study revealed the possible role of hs-CRP and several GI- hormones in the pathogenesis of obesity-associated diseases and MetS. Additional works are needed to elucidate the possible underlying mechanisms and clarify several controversies in this issue.

Context. Irisin, a cleaved product of fibronectin type III domain-containing protein 5 (FNDC5), has been proposed as a key molecular link between energy metabolism and reproductive regulation. Emerging evidence suggests that it modulates hypothalamic-pituitary-gonadal (HPG) activity and oxidative balance, but its reproductive effects in males remain insufficiently defined. Objective. To evaluate the endocrine, antioxidant, and reproductive responses to exogenous irisin administration in healthy male Wistar rats. Design. A controlled, time-course experimental study was conducted to assess hormonal, biochemical, and sperm-related outcomes following irisin treatment. Subjects and Methods. Twenty-four adult male Wistar rats were randomly allocated to Control (saline) or Treated (irisin, 200 ng/kg, subcutaneous) groups, with sample collection on days 10, 20, and 30. Serum levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, lipid profiles, and oxidative stress biomarkers [malondialdehyde (MDA), reactive oxygen species (ROS), total antioxidant capacity (TAC)] were analyzed. Sperm count, motility, and morphology were also evaluated. Results. Irisin administration significantly increased serum GnRH, LH, FSH, and testosterone concentrations (p < 0.001), indicating activation of the HPG axis. Lipid parameters remained unchanged. Oxidative stress markers were favorably modulated, with reduced MDA and ROS (p < 0.05) and a progressive increase in TAC over time (p < 0.05, group × day interaction). Sperm count was higher in the Treated group (p < 0.05), while motility and morphology were not significantly affected. Conclusions. Subcutaneous irisin administration enhances reproductive hormone secretion, improves antioxidant capacity, and increases sperm production in male rats without altering lipid metabolism. These findings suggest that irisin may serve as a potential therapeutic modulator of male reproductive function, particularly under conditions involving oxidative stress or endocrine disruption.

Background. Fine-needle aspiration biopsy (FNAB) is the most accurate diagnostic method to assess the malignancy risk of thyroid nodules. However, nondiagnostic results may delay diagnosis, cause unnecessary interventions, and distress patients. Aim. We aimed to determine whether a correlation exists between patients’ situational anxiety, pain perception and non-diagnostic cytology results. Methods. The prospective study included patients who underwent thyroid FNAB at the Endocrinology Clinic of Sultan Abdulhamid Training and Research Hospital between 11/2022 and 02/2023. The State-Trait Anxiety Inventory (STAI) questionnaire and visual analogue scale (VAS) assessed situational anxiety and pain in patients undergoing biopsy procedures. We evaluated whether the STAI-S and VAS score is related to non-diagnostic results. Results. Of the 119 patients included in the study, 98 were female, and 21 were male. 25 (21%) nodules were non-diagnostic. The patients' mean STAI-S score before the biopsy was 47.31±12.37, and the mean VAS score after the thyroid biopsy was 2.57±1.51. A statistically significant relation was found between the patient's STAI-S score and VAS score and the cytology result of non-diagnostic (p= 0.001 and p=0.008). In univariate logistic regression, high pre-procedural anxiety (OR:3.09, 95% CI:1.07-8.94, P =0.037) and VAS score (OR:1.57, 95% CI: 1.17-2.10, P =0.002) were associated with non-diagnostic cytology. In multivariate logistic regression analysis, VAS score (OR: 1.59, 95% CI: 1.07-2.34, p=0.019) was still an independent factor related to specimen adequacy. Conclusions. Anxiety level and pain perception during FNAB may be considered risk factors for nondiagnostic cytology. Thus, reducing anxiety and pain may decrease the incidence of non-diagnostic outcomes.