ACTA ENDOCRINOLOGICA (BUC)

Testosterone influences cancer development. This in vitro experiment was exerted to determine the association of testosterone with human colorectal cancer(HT29), glioblastoma (A172) and human embryonic kidney(HEK293) cells proliferation. HT-29, A172 and HEK293 cell lines were cultured in standard growth medium, then randomly divided into control group (not exposed to testosterone) and groups exposed to 1, 10, 100 and 1000 μg/mL of testosterone. Cell viability was quantified by MTT assay. Statistical analysis was performed using ANOVA. Viability of HEK293 cells significantly increased in groups exposed to 1 μg/mL and decreased in groups exposed to 100 and 1000 μg/mL of testosterone compared to control group (P<0.05, P<0.05 and P<0.001, respectively). Viability of HT29 cells significantly increased in groups exposed to 10 and 100 μg/mL of testosterone and significantly decreased when exposed to 1000 μg/mL of testosterone compared to control group (P<0.05, P<0.001 and P<0.001, respectively). Viability of A172 cells significantly decreased in groups exposed to 100 and 1000 μg/mL of testosterone compared to control group (P<0.001). In conclusion, different doses of testosterone have enhancing or suppressive effects on HEK293, HT29 and A172 cells proliferation; according to which, considering clinical use of testosterone therapy for cancer treatment is a highly controversial issue.

The aim of this study was to examine the highglucose and high fatty acid status effect on the development of atherosclerosis. Materials and Methods. We used rat thoracic aorta smooth muscle cell line A7r5. We investigated mechanisms underlying high-glucose and high fatty acid (oleic acid) conditions on vascular smooth muscle cell (VSMC) mimicking concurrent status of diabetes and dyslipidemia. Results. Glucose-oleic acid stimulated cell proliferation and migration while the proliferating cell nuclear antigen (PCNA) level and matrix metalloproteinase (MMP)-2 were activated. In addition, the expressions of connective tissue growth factor (CTGF) and fatty acid synthase (FASN) enhanced by glucose-oleic acid were increased. The proliferation signal mediated by glucoseoleic acid condition was demonstrated via CTGF/FASN, while MMP-2 was regulated by CTGF but not FASN. Conclusion. Oleic acid in the presence of high glucose level can induce VSMC proliferation and migration leading to diabetes-associated vascular atherosclerosis. Furthermore, via activation of CTGF, increased expression of FASN suggested a possibility of lipogenesis in VSMC which may also contribute to diabetes-associated vascular atherosclerosis.

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) plays an important role in the regulation of cellular energy metabolism, and it is involved in obesity and type 2 diabetes mellitus (T2DM). Its expression is elevated in the liver of T2DM mouse models. Literature reports show that chronic β2 stimulation improved insulin sensitivity in T2DM. Objectives. We aimed to test the hypotheses that chronic β2 stimulation-induced improvement in insulin sensitivity involves changes in the expression of PGC-1α and glucose transporter 4 (GLUT4). Animals and Methods. We fed a locally inbred, 8 months old mice, a high fat diet (HFD) to induce diabetes. These mice gained weight and became insulin resistant. The β2 agonist salbutamol had a beneficial effect on both glucose tolerance and insulin sensitivity after 4 weeks. Results. Salbutamol beneficial effect persisted after 4 weeks of its discontinuation. HFD caused an up regulation of the hepatic PGC-1 α expression by 5.23 folds (P< 0.041) and salbutamol reversed this effect and caused a down regulation by 30.3 folds (P< 0.0001). PGC-1 α and GLUT4 expression in the muscle was not affected by salbutamol (P> 0.05). Conclusion. Down regulation of the liver’s PGC- 1 α contributes to the beneficial effect of the chronic β2 stimulation on glucose tolerance and insulin sensitivity in T2DM mice.

Context. Primary hyperparathyroidism (PHPT) is often associated with thyroid disorders like nodular goiter, Hashimoto’s thyroiditis (HT) and Graves’ disease. Objective. Our aim was to explore whether the coexistence with HT affects bone metabolism in patients with PHPT. Design. This was a comparative cross-sectional study carried out in a tertiary inpatient endocrine center from January 2018 through December 2020. Subjects and Methods. A total of 234 patients were diagnosed with PHPT at our endocrine center. One hundred of them were included in the study - 50 with PHPT only and 50 with PHPT and HT. Two control groups were defined: 37 with HT and 37 without PHPT and HT. Serum markers of calcium-phosphate metabolism, bone markers (RANKL, Osteoprotegerin, β-CTX, Osteocalcin) and interleukin-17A were measured. Results. The frequency of HT among patients with PHPT was 37.6% (95% CI 31-43%) and did not differ significantly from that in the general population, 32.5% (95% CI 30-35%). Age, BMI, markers of calciumphosphate metabolism, bone markers and interleukin-17A weren’t significantly different in PHPT with and without HT or between the two control groups. The participants with PHPT had higher levels of interleukin-17A, β-CTX and Osteocalcin (p<0.05) than those without the PHPT. RANKL and Osteoprotegerin in these groups did not differ. Interleukin-17A correlated positively with serum calcium, PTH and RANKL and negatively with serum inorganic phosphate and 25(OH)D. Controlling for HT and age did not change the correlation. Conclusions. In our study, HT has not additional effect on bone metabolism in the patients with PHPT. Higher levels of interleukin-17A in PHPT suggest a possible role in the PTH-induced bone remodeling.

Background. Dual-energy X-ray absorptiometry (DXA) allows measurement of whole body (WB) and regional bone mineral content (BMC) and density (BMD). Objective. To measure WB and regional bone area, BMC and BMD (arms, legs, ribs and pelvis) in women of different ages. Subjects and Methods. 140 women participated (age range 20-75 yrs). Three subgroups were built: 20-44 yr (30 premenopausal women), 45-59 (80 women), and 60-75 (30 women). WB DXA was performed on a Hologic QDR 4500 A bone densitometer (Hologic Inc., Bedford MA). WB BMD T-scores were calculated by using the manufacturerprovided and the NHANES 1999-2004 reference databases, while the WB BMC Z-scores - based on the latter. Statistical analysis was performed on an IBM SPSS Statistics 19.0 for Windows platform (Chicago, IL). Results. WB BMC and BMD Z-scores were consistently lower than the reference databases showing a difference of about 0.4 – 0.5 SD. The arms, legs and ribs lost more BMC after the age of 50-55, while the pelvis – much earlier. The total decreases in BMC were highest in the pelvis (26.36 %), followed by the arms (16.81 %) and whole body (15.91 %), while the bone area decreased mostly in the pelvis (13.23 %). Conclusion. The age-related declines in regional BMC, bone areas and BMD follow different patterns in appendicular and axial bones.

Aims. To investigate the changes in the miRNAs and mRNAs expressed in the liver upon induction of “hyperresistinemia”. Methods. We identified mRNA and miRNAs that were differentially expressed between normal and resistin-treated liver tissue using microarrays. Expression was validated using quantitative RT-PCR (qRT-PCR). The putative targets and pathways of the differentially expressed miRNAs and mRNAs were investigated, respectively, using various computational algorithms. In addition, the interactions between differentially expressed miRNAs and mRNAs were analyzed. Results. After the filtration of the signals below the threshold level, we identified 34 miRNAs and 875 genes with expression levels different by more than 1.5-fold and 2.0-fold, respectively, between the two groups. These observations were confirmed by qRT-PCR. Bidirectional prediction analyses showed that the differentially expressed miRNAs may be inversely regulated by their predicted targets. Conclusion. Hyperresistinemia results in changes in the miRNAs and mRNAs expressed in the liver.

Background. Nephrogenic diabetes insipidus (NDI) is a disease characterized by a defective response to the antidiuretic hormone (ADH) of the renal collecting duct leading to a decline in the ability of the pro-urine concentration. Case presentation. A 23-year-old man presented with an over 20-year history of polyuria concomitant with hydronephrosis. The diagnosis of NDI was established by gene analysis as well as a water-deprivation and vasopressin test. All exons of arginine vasopressin V2 receptor (AVPR2) gene were amplified and sequenced. A novel hemizygous intragenic inframe deletion, cDNA 255th bp to 263th bp in exon 2 of AVPR2, was identified. These relevant translations from the 85th amino acid Asp to 88th amino acid Val were missed and replaced by amino acid Glu. After treating the patient with hydrochlorothiazide, his symptoms improved significantly. Conclusion. The genetic analysis revealed a novel X-linked intragenic inframe deletion, AVPR2 gene cDNA 255th bp to 263th bp, causing NDI.

Female sex steroids play considerable roles in body weight and insulin physiology.\r\nEnhanced or reduced female sex steroids affect insulin sensitivity.\r\nThe aim of the present study was to examine the effects of female sex steroids on body\r\nweight and insulin sensitivity through ovariectomy and progesterone or estradiol\r\nadministration in rats.\r\nMaterials and Methods. 7 week old female albino (Wistar) rats were used in our study.\r\nAnimals were randomly divided into control, uni-ovariectomised, bi-ovariectomised, sham,\r\nvehicle receiving sham and vehicle or hormone receiving female groups. Progesterone (20\r\nmg/kg/day) or estradiol valerate (200 &#956;g/kg/day) were injected subcutaneously, starting on the\r\nthird day after surgery and continued at daily intervals. After 4 weeks, animals were measured\r\nfor body weight and killed. Following serum collection, fasting serum insulin and glucose were\r\nmeasured and fasting glucose to insulin ratio was considered as index of insulin sensitivity\r\nwhich were compared statistically between the groups.\r\nThe results showed increased insulin sensitivity (glucose to insulin ratio) (IS) and body\r\nweight (BW) in both bi-ovariectomised (bi-ovx) (IS=14.76, BW=237.40 g) and uniovariectomised\r\n(IS=11.33, BW=225.53) rats compared with the control group (IS=9.36,\r\nBW=205.32) (p<0.01). Progesterone or estradiol replacement in bi-ovx rats was followed by\r\nincreased or decreased body weight (264.50 or 205.10) and increased or decreased insulin\r\nsensitivity (20.38 or 8.50) compared with bi-ovx rats, respectively (p<0.05). In nonovariectomised\r\nrats, administration of progesterone resulted in increased and of estradiol in\r\ndecreased body weight (220.6 g and 185.35 g) and insulin sensitivity (18.36 and 5.35)\r\ncompared with control animals (p<0.01).\r\nConclusively, our findings indicate that progesterone is enhancer and estradiol is reducer\r\nof insulin sensitivity in rats. In addition, weight gain after ovariectomy or progesterone\r\ntreatment and weight loss following estradiol treatment did not probably contribute in acting on\r\ninsulin sensitivity.

Aim. To establish a nomogram combining preoperative ultrasonic and clinical features for predicting lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) metastasis in papillary thyroid carcinoma (PTC) patients. Methods. Preoperative ultrasonic and clinical variables of patients with PTC from 2014 to 2021 were retrospectively analyzed. The risk factors associated with LN-prRLN metastasis were identified and validated through a developed nomogram model based on univariate and multivariate logistic regression analysis. Results. A total of 615 patients (690 lesions) were enrolled for the training dataset and 207 patients (226 lesions) for the validation dataset with 54 (6.57%) patients developing LN-prRLN metastasis. Multivariate logistic regression analysis demonstrated that the preoperative ultrasound measurement of larger tumors (≥20 mm), higher TI-RADS category (category 5), and higher thyroglobulin level (9.86 ng/mL) in patients with PTC were predictive factors for LN-prRLN metastasis. The nomogram model was established and verified yielding a relatively good predictive performance in the training and validation dataset (AUC: 0.868 vs. 0.851). Conclusions. The nomogram combining preoperative ultrasonography with clinical features in this study is highly predictive of LN-prRLN metastasis in patients with PTC, which may provide more personalized recommendations for clinicians in preoperative decisionmaking for complete dissection of LN-prRLN.

Objective. To investigate the correlation between serum levels of 25-hydroxy vitamin D [25(OH)D] and the visceral fat area of patients with type 2 diabetes mellitus (T2DM) in the context of different bone mass. Materials and Methods. A total of 180 patients with T2DM were randomly selected for bone mineral density (BMD) examination. According to the results, they were divided into three groups: T2DM normal bone group (group A); T2DM bone mass reduction group (group B); T2DM osteoporosis group (group C). Result. Serum 25(OH)D levels in NC group, A group, B group and C group decreased in turn, and Visceral fat area (VFA) in group B and group C were significantly higher than those in group A and NC [(29.41±4.87) vs. (22.76±4.23) vs. (17.78±3.61) vs. (9.70±3.01), P<0.05], [(117.76±38.79), (125.08±37.90) vs. (89.79±26.51), (97.53±28.61), P<0.05]. Pearson correlation analysis showed that L1-L4 lumbar vertebrae bone density was positively correlated with 25(OH)D and VFA; left femoral neck bone density was positively correlated with 25(OH)D, and negatively correlated with VFA. Conclusion. Serum 25(OH)D and VFA may be associated with the development of T2DM combined with OP.