ACTA ENDOCRINOLOGICA (BUC)

Leptin is much more than a simple sensor of body fat levels. Its biological activities, include angiogenesis, osteogenesis and modulation of the immune and reproductive systems. There are no reports on fluctuations of the level in normal human functional glandular epithelium during the menstrual cycle. Objective. We aimed to determine the expression level of the leptin receptor by immunohistochemistry and to correlate this with estrogen and progesterone receptor levels in normal endometrial tissue throughout the menstrual cycle. Study design. Thirty-seven paraffin wax blocks of biopsy specimens of histologically normal endometrium were evaluated and classified according to the stage of the menstrual cycle during the 2004–2006 period. Results. The OB-R level underwent fluctuations during the menstrual cycle in the different tissue compartments; these were most marked in the functional glandular epithelium and during the proliferative stage. OB-R levels were correlated positively with the expression levels of estrogen and negatively with those for progesterone receptors, suggesting that these steroids modulate the expression of OB-R in vivo. Conclusion. This finding underscores the importance of considering the menstrual cycle stage for studies seeking possible impacts of the OB-R on reproductive pathology, because its expression level varies with the hormonal environment.

Introduction. Symptoms related to hypersecretion of hormones in patients with pituitary adenomas do not always correlate with immunohistochemical staining results. Objective. To evaluate the relationship between the pituitary adenomas hormone immunoexpressions and endocrine presentations. Patients and methods. The clinical status and immunoexpression of 72 patients who underwent transsphenoidal surgery for pituitary adenomas were analyzed. Results. Macroadenomas were diagnosed in 51 cases (70.84%), while microadenomas were found in 21 cases (29.16%). The 72 adenoma specimens were divided into 22 monohormonal, 21 plurihormonal, 21 immunonegative and 8 unreliable specimens. The positive immunohistochemical staining results occurred as follows: prolactin and growth hormone 25% each, adrenocorticotropic hormone 13.89%, thyroid-stimulating hormone 5.56%, leuteinizing hormone and follicle-stimulating hormone 12.5%, glycoprotein hormone alpha-subunit 22.22%. Statistically significant relationships between the immunohistochemical presentation and the preoperative diagnosis were found for prolactin and hyperprolactinemia, growth hormone and acromegaly and adrenocorticotropic hormone and Cushing’s syndrome. Conclusions. The lack of full concordance between the clinical presentations and immunohistochemical staining was mainly a result of the presence of nonfunctioning adenomas, plurihormonal adenomas and unreliable specimens. The morphometric method introduced in this study, utilizing the immunoexpression index, provided a very precise evaluation of pituitary adenomas pathology.

Context. MicroRNAs (miRNAs) are short noncoding RNAs involved in posttranscriptional regulation of gene expression that influence various cellular functions including glucose and lipid metabolism and adipocyte differentiation. Objective. The aim of this study was to evaluate the levels of miR-34a and miR-149 and their relationship with metabolic parameters in obese children and adolescents. Design. Seventy children and adolescents were enrolled in the study. Plasma levels of microRNAs were evaluated by real-time PCR using SYBR green and analyzed by ΔCt method. Plasma concentrations of visfatin and insulin were measured by ELISA method. Glucose and lipid profile were determined colorimetrically. HOMA-IR was calculated and used as an index of insulin resistance (IR). Results. miR-34a was significantly lower in subjects with insulin resistance compared to obese children with normal insulin sensitivity. There was an inverse relationship between miR-34a levels and both insulin and HOMA-IR. On the other hand, miR-149 was significantly correlated with visfatin. There was no significant difference in miR-34a and miR-149 between obese and normal weight subjects. Conclusions. miR-34a is associated with insulin and HOMA-IR and thus seems to be involved in IR. miR- 149 is inversely associated with visfatin levels which could be indicative of anti-inflammatory effect of this miRNA.

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The effects of daily evening melatonin (MT) injections on plasma T3 and T4 and pineal thyroxin 5’-deiodinase (5’-D) activity in euthyroid and hypothyroid rats were investigated. Circulating levels of thyroid hormones were monitored and 5’-D activity was measured in pineal homogenates throughout the daily light-dark cycle. In the euthyroid group, T3 and T4 concentrations and pineal 5’-D activity gradually increased during the L-phase of the L/D cycle to reach maximum levels early at night. The lowest values for pineal 5’-D activity and T4 were obtained later at night when endogenous MT production was the highest. MT treatment induced an opposite circadian variation of plasma T3, T4 and pineal 5’-D activity with significant increases later at night and decreases early at night vs. the control group. In the hypothyroid group, the serum T4 and T3 concentrations significantly decreased at all moments assayed. Treatment with MT did not lead to significant changes in the propylthiouracil effect on T4 and T3 levels, but maintained the biphasic response, observed in the MT treated euthyroid group. The increases induced by PTU in pineal 5’-D activity during the light phase, were reduced from 43.61 ? 2.35 ng T3/mg protein / h to 33.36?2.87 ngT3/mg protein/h (p=0.01) by MT injections. In conclusion, the results rendered the presence of the 5’-D in the rat pineal, its activity showing a circadian pattern similar to the circulating T4 levels. The MT treatment induced an opposite circadian variation of serum T3, T4 and pineal 5’-D activity suggesting an interaction between the light/dark cycle, 5’-D activity and responsiveness to MT.

Background. Following recent years, there is an increased body of literature on the connections that might exist between type 2 diabetes mellitus and the efficiency of bariatric surgery in its reversal compared to other medical approaches such as dieting. Aim. To induce experimentally type 2 diabetes mellitus in rats in order to observe the effects of bariatric surgery in the recovery as well as the reestablishment of normal insulin levels in order to extend the findings in house animals. Materials and methods. This study was conducted in three stages: the first consisted in inducing type 2 diabetes mellitus (T2DM) in 40 young Wistar male rats, by initially feeding them human food high in vegetal fats, oleaginous seeds, simple and complex carbohydrates, sugars, lipids, fats, proteins and fructose for a period of 8 weeks followed by a single low dose of streptozotocin (STZ), administered through intraperitoneal injection. The second stage of the study started when the rats became obese and therefore qualified for the bariatric procedure and the third stage consisted of post-operation supervision and care. The surgical procedure, performed on 10 obese rats, consisted in reducing the size of the stomach by partial gastrectomy of a 1.5 – 2.0 cm wide and 6.5 – 7.5 cm long area on the large curvature. Results. Showed rapid improvements in body weight and blood sugar control after 9 days. Conclusion. After putting the rats on a diet high in carbohydrates, sugars, lipids and fats and administering them STZ, the induction of type 2 diabetes was successful and the partial gastrectomy led to a better blood sugar control. The bariatric procedure provides a faster therapeutic response than conventional diets.

Context. Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and cleaves angiotensin II to Angiotensin (1–7), annihilating the deleterious effects of angiotensin II which is known to be a strong activator of oxidative stress. Objective. We aimed to evaluate the relationship of oxidative stress to urinary ACE2 (uACE2) in type 2 diabetes mellitus (T2DM) patients. Design. We included consecutive normo or microalbuminuric T2DM patients in an observational transversal study. Routine laboratory investigations, plasma malondialdehyde (MDA, fluorimetric thiobarbituric method) as a marker of prooxidant capacity and superoxide dismutase (SOD, cytochrome reduction method) and catalase (CAT) activity (in erythrocyte lysate by the modification of absorbance method) as two measures of serum antioxidant capacity and uACE2 (ELISA method) were assessed. Results. MDA showed a negative correlation with SOD (r=-0.44, p=0.001), CAT (r=-0.37, p=0.006), uACE2 (r=-0.33, p=0.016) and a positive correlation with glycated haemoglobin (HbA1c) (r=0.49, p<0.001) and associated cardiovascular disease (r=0.42, p=0.001). CAT as also positively correlated to uACE2 (r=0.29, p=0.037). SOD was also negatively correlated with glycemia (r=-0.71, p<0.001) and HbA1c (r=-0.53, p<0.001). Patients with lower MDA (when divided according to median value of 3.88 nmol/ mL) had higher uACE2 57.15(40.3-71.2) pg/mL compared to 38.5(31.8-45.95) pg/mL in patients with higher MDA (p<0.001). In multivariate logistic regression uACE2 was the only predictor for MDA above or below its median (OR=0.94, 95%CI[0.90-0.98], p=0.002). Conclusion. Increased prooxidant serum capacity is associated with lower uACE2 levels in T2DM patients.

Objective. Adrenal incidentaloma are lesions which are stated incidentally by imaging methods when there is no suspicion of any disease in adrenal gland. Inappropriate Jak2 signaling causes some solid and hematological malignancies. But the Jak2 mutation has not been previously evaluated with regard to adrenal tumors. In this study, we aimed to positivity of the Jak2 mutation in patients with non functioning adrenal incidentaloma (NFAI). Methods. 45 (38 female–7 male) patients, who were followed due to NFAI at Tepecik Training and Research Hospital, Department of Endocrinology and Internal Medicine between February 2014 and March 2015, and 45 (31 female–14 male) healthy controls were included in the study. Results. The average age was 54.02±11.7 years and 38 patients were female, 7 were men. All patients underwent the following analyses for excluding a functioning adrenal mass, overnight dexamethasone suppression test, 24 hour urinary metanephrine and normetanephrine, plasma aldosterone/ renin activity ratio. Jak2 mutation of the patients who were diagnosed as NFAI was all negative. Conclusion. We could not identify the JAK2 gene mutation positivity in any sample. Since other possible mechanisms may throw fresh light on the etiology of adrenal incidentaloma, further clinical studies are needed on this subject.