Age, Body Mass Index, and Waist-to-Hip Ratio Related Changes in Insulin Secretion and Insulin Sensitivity in Women with Polycystic Ovary Syndrome: Minimal Model AnalysesRead the full article
International Journal of Endocrinology publishes original research articles and review articles that provide insights into the endocrine system and its associated diseases at a genomic, molecular, biochemical and cellular level.
International Journal of Endocrinology maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.
Latest ArticlesMore articles
Testosterone Deficiency Promotes Hypercholesteremia and Attenuates Cholesterol Liver Uptake via AR/PCSK9/LDLR Pathways
Background. Testosterone deficiency is reportedly correlated with an elevation of cholesterol in plasma, but the mechanism remains unclear. Our objective was to investigate the effects of testosterone deficiency on cholesterol metabolism and the corresponding molecular changes in vivo and in vitro. Methods. SD rats were randomized into three groups: sham-operated (SHAM), subtotal orchiectomized (SO), and orchiectomized (ORX) and fed for 8 weeks. HepG2 cells were cultured with medium containing testosterone with the final concentrations of 0, 10, 30, and 300 nM. Method of isotope tracing and fluorescence labelling was adopted to investigate cholesterol metabolism. Several key molecules of cholesterol metabolism were also analyzed. Results. SO and ORX rats displayed dysfunctional liver uptake of cholesterol. HepG2 cells incubated with testosterone of lower and excessive level exhibited reduced capacity of cholesterol uptake. Further investigation revealed that lack of testosterone induced increased proprotein convertase subtilisin/kexin type 9 (PCSK9) and decreased low-density lipoprotein receptor (LDLR) both in vivo and in vitro. Moreover, the androgen receptor (AR) antagonist flutamide mimicked the effects of testosterone deficiency on PCSK9 and LDLR indicating the role of AR as a mediator in triggering attenuating liver cholesterol uptake in which testosterone instead of dihydrotestosterone (DHT) is the major functional form of androgen. Conclusion. Testosterone deficiency attenuated cholesterol liver uptake mediated by the PCSK9-LDLR pathway, in which AR and testosterone without transforming to DHT play important roles.
Serum 25(OH)D Levels Modify the Association between Triglyceride and IR: A Cross-Sectional Study
Background. Triglycerides and 25(OH)D had been reported as correlates of IR, but the results suggest substantial heterogeneity across races. In addition, little research reported on whether different 25(OH)D levels affect triglycerides and IR. Therefore, a similar study on the US population would be a great addition to the current one. This study investigated the association between triglycerides and IR at different 25(OH)D levels. Methods. A total of 19,926 participants were included, each containing specific indicators for the study project. IR was estimated as a HOMA-IR index ≥2.73. Four multivariate logistic regression models were developed to analyze the association between TG and IR and whether different 25(OH)D levels influenced this association. Smoothed fitting curves were plotted. Results. Triglyceride was significantly associated with IR (OR: 1.3, 95 CI %), while this association received different 25(OH)D levels ( for interaction <0.001). The effect value OR was 1.33 with the high levels, and its effect value OR was 1.28 with the low levels. Conclusion. This study demonstrates that triglyceride levels are significantly associated with insulin in the US adult population and can be used as a predictor of IR. This correlation was compromised at different 25 (OH)D levels, so future studies need to be explored in more ethnically diverse contexts.
Forskolin Stimulates Estrogen Receptor (ER) α Transcriptional Activity and Protects ER from Degradation by Distinct Mechanisms
Estradiol action is mediated by estrogen receptors (ERs), a and ß. Estradiol binding initiates ER-mediated transcription and ER degradation, the latter of which occurs via the ubiquitin-proteasome pathway. Inhibition of proteasome activity prevents estradiol-induced ERα degradation and transactivation. In ER-positive GH3 cells (a rat pituitary prolactinoma cell line), forskolin, acting via protein kinase A (PKA), stimulates ERα transcriptional activity without causing degradation, and proteasome inhibition does not block forskolin-stimulated transcription. Forskolin also protects liganded ERα from degradation. In the current study, we first examined ERα and ERβ transcriptional activity in ER-negative HT22 cells and found that forskolin stimulated ERα-, but not ERβ-dependent transcription, through the ligand-binding domain (LBD). We also identified four mutations (L396R, D431Y, Y542F, and K534E/M548V) on the ERα LBD that selectively obliterated the response to forskolin. In GH3 cells, transfected ERα mutants and ERβ were protected from degradation by forskolin. Ubiquitination of ERα and ERβ was increased by forskolin or estradiol. ERα ubiquitination was diminished by a mutated ubiquitin (K48R) that prevents elongation of polyubiquitin chains for targeting the proteasome. Increased ERα ubiquitination was not affected by the deletion of the A/B domain but significantly diminished in the F domain deletion mutant. Our results indicate distinct and novel mechanisms for forskolin stimulation of ERα transcriptional activity and protection from ligand-induced degradation. It also suggests a unique mechanism by which forskolin increases unliganded and liganded ERα and ERβ ubiquitination but uncouples them from proteasome-mediated degradation regardless of their transcriptional responses to forskolin.
Serum PTH Associated with Malnutrition Determined by Bioelectrical Impedance Technology in Chronic Kidney Disease Patients
Purpose. Chronic malnutrition and cachexia are common in chronic kidney disease (CKD), and importance should be given to these complications because they affect the patient’s quality of life and prognosis. This study analyzed the correlation between the serum PTH level, nutritional status, and body composition of patients with CKD. Methods. CKD patients were enrolled in Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical University, from December 1, 2016, to November 30, 2020. Bioelectrical impedance technology was applied to estimate the body composition. The characteristics of the body composition were compared among different stages of CKD patients, and then the correlation between PTH and body composition was analyzed. Results. 205 CKD patients were enrolled. Twenty-five patients were in stage 1 or 2 of CKD, 78 patients were in stage 3 or 4, 31 patients were in stage 5 without dialysis (referred to as CKD stage 5A), and 71 patients were in stage 5 with dialysis (referred to as CKD stage 5B). Body composition analysis showed that the patients had a phase angle (PA) of 5.02 ± 1.07°, a percentage of body fat (PBF) of 27.74 ± 8.8%, and a skeletal muscle mass index (SMI) of 7.4 ± 1.34 kg/m2. PBF peaked in the CKD stage 3/4 group and gradually decreased with the progression of CKD. The PA and SMI differed significantly between the CKD stage 1/2 and stage 5B groups. The proportion of low SMI did not differ significantly between the CKD stage 1/2 and stage 3/4 groups, but it was obviously higher in the CKD stage 5A and 5B groups. PTH was significantly correlated with BMI, hemoglobin, albumin, total cholesterol, triglycerides, and SMI. Binary logistic regression of low SMI showed that the odds ratio for PTH levels was greater than the upper limit of the normal range, which was 11.769 (, 95% confidence interval: 1.078–128.536), and the model predictive power was 0.986 after correction for age, sex, height, weight, hemoglobin, serum calcium, serum phosphorus, serum total cholesterol, serum triglyceride, and basal metabolic rate. Conclusions. Bioelectrical impedance analysis might be useful in estimating the nutritional status of CKD patients in terms of fat and muscle parameters. High levels of PTH are an independent risk factor for developing low SMI in CKD patients.
Harmful Consequences of Proton Pump Inhibitors on Male Fertility: An Evidence from Subchronic Toxicity Study of Esomeprazole and Lansoprazole in Wistar Rats
Proton pump inhibitors (PPIs) are frequently prescribed as gastric acid-suppressing agents. Nevertheless, there is limited evidence supporting the risk of detrimental effects of PPIs on male fertility. The purpose of the current study was to evaluate the effect of subchronic use of proton pump inhibitors on male fertility. Seventy adult male Wistar rats were assigned into seven groups. The normal control group orally received solvent only. Groups 2, 3, and 4 were orally given esomeprazole while groups 5, 6, and 7 received lansoprazole at 2.5, 5, and 10 mg/kg/day, respectively. After 45 days of treatment, blood samples, epididymis, and testis were collected. Sperm count, motility, and morphology were determined. The level of hormones such as testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) and oxidative status of testis tissue, such as superoxide dismutase, catalase, reduced glutathione, malondialdehyde (MDA), and nitric oxide (NO) were estimated. Results demonstrated a significant decline in sperm count, motility, morphology, testosterone, and catalase at 10 mg/kg/day and GSH at 2.5 mg/kg/day. A significant increase in FSH, LH, and MDA at 10 mg/kg/day and NO at 2.5 mg/kg/day was found as compared to the control group. The pathological alterations specifically dilation of Leydig cells, vacuolization, and degeneration of the seminiferous tubules were also evident. It is concluded that PPIs had caused male reproductive toxicity in Wistar rats due to altered levels of hormones such as testosterone, FSH, and LH, elevated levels of NO, and oxidative stress.
Contrast-Enhanced Ultrasound: An Effective Method for Noninvasive Diagnosis of Mummified Thyroid Nodules
Mummified thyroid nodules are a special type of thyroid nodule, which is benign, but is often diagnosed as malignant by ultrasound. This study investigated the usefulness of contrast-enhanced ultrasound (CEUS) in the diagnosis of mummified nodules. 66 patients with mummified nodules were divided into two groups: a no-enhancement group and a low-enhancement group. 32 patients with papillary thyroid carcinoma (PTC) were recruited in control group. In the no-enhancement group, CEUS showed that there was no contrast agent entering the nodules, with or without a little dot enhancement or regular ring enhancement around the nodules. The low-enhancement group showed low enhancement inside nodules, which was similar to that in the PTC group. In semiquantitative time-intensity curve analyses, intensity maximum of the central area of nodules in the low-enhancement group was lower than that in the PTC group () and time to peak of the central area of nodules in the low-enhancement group was lower than that in the PTC group (). The results demonstrate that CEUS could be used to effectively diagnose mummified nodules, obviating the need for patients to undergo invasive examination such as biopsy or even surgery.