Hormones最新文献

Background

Glucocorticoid-induced osteoporosis is a leading secondary cause of osteoporosis. Cullin-1 (CUL1) levels are abnormally elevated in patients with osteoporosis, but the underlying mechanism remains unclear. The purpose of this study was to elucidate the mechanism of action of CUL1 in a glucocorticoid (dexamethasone, Dex)-induced osteoporosis model.

Methods

C57BL/6J mice were intraperitoneally injected with Dex to establish an osteoporosis model. Mouse femur bone injury and bone formation were detected using hematoxylin-eosin or Masson staining. Apoptosis and cell cycle distribution were determined by flow cytometry. Alkaline phosphatase (ALP) activity and calcified nodules were monitored using ALP and Alizarin Red S staining. The molecular mechanism was validated by co-immunoprecipitation (Co-IP) and ubiquitination assays.

Results

CUL1 expression was enhanced in the Dex-induced osteoporosis mouse model. CUL1 silencing moderated the Dex-induced cell proliferation and osteogenesis inhibition. Moreover, CUL1 promoted the ubiquitination and degradation of ASAP1 via the SKP1-CUL1-F-box (SCF)-FBXW7 complex. CUL1 induced apoptosis and repressed osteogenesis by ASAP1. CUL1 silencing alleviated the Dex-induced osteoporosis in mice.

Conclusion

CUL1 suppressed osteoblast proliferation and osteogenesis by promoting ASAP1 ubiquitination via the SCF-FBXW7 complex in glucocorticoid-induced osteoporosis.

Graphical Abstract

There are accumulating levels of scientific knowledge concerning the dietary recommendations for the prevention of type 2 diabetes mellitus (T2DM). Purpose: This systematic review presents the most recent scientific knowledge concerning dietary recommendations for T2DM published in the English language by various scientific societies during the past 10 years. Methods: The recommendations are herein presented and discussed in the light of a critical, evidence-based appraisal aiming to provide a comprehensive guide for the clinician in daily practice. Results: In the case of overweight or obesity, the cornerstone of the primary prevention of T2DM is the combination of a healthy body weight (body mass index < 25 kg/m²) or a reduction of fat by at least 7% and the implementation of at least 150 min of moderate physical activity per week. Restriction of calories and of dietary fat is recommended, the latter as well as several dietary patterns providing a holistic approach to dieting and all having been correlated with decreased risk of T2DM. Among these dietary patterns are the Mediterranean diet, the DASH diet (Dietary Approaches to Stop Hypertension), the low-glycemic diet, and the HEI-Healthy Eating Index and AHEI-Alternative Healthy Eating Index. Micronutrient deficiencies of, for example, vitamin D, chromium and magnesium, may be associated with insulin resistance in T2DM. Conclusion: Overall, the combination of nutrition through dietary patterns that are mainly plant-based and which emphasize wholegrains, legumes, nuts, fruits, and vegetables and that include only small percentages of refined and processed foods, together with physical activity, has been associated with decreased T2DM risk.

Objective

This study aimed to explore the associations of tobacco smoke exposure (TSE) and heavy metal exposure on sex hormones and the joint effects between them in adult males.

Methods

The study used data of 2244 adult males from the National Health and Nutrition Examination Survey (NHANES, 2013–2016). Weighted linear regression models were used to calculate their beta (β) coefficients and corresponding confidence interval (95% CI), which assessed the joint effects of TSE and heavy metals on sex hormones.

Results

Sex hormone-binding globulin (SHBG) showed a positive association with increased per standard deviation (SD) for cotinine (β=0.024 [0.004, 0.043]; P<0.001), lead (β=0.021 [0.002, 0.039]; P=0.028), and cadmium (β=0.034 [0.015, 0.053]; P<0.001). Manganese was positively associated with estradiol (E2) (β=0.025 [0.009, 0.042]; P=0.002). The subjects with higher cadmium levels were more likely to have higher total testosterone (TT) (β=0.042 [0.023, 0.062]; P<0.001). TSE and lead exerted synergistic effects on TT (p for interaction = 0.015) and E2 (p for interaction = 0.009), as also did TSE and cadmium on SHBG (p for interaction = 0.037). Compared with the reference group, TSE participants who were exposed to high concentrations of lead, cadmium, mercury, and manganese had significantly elevated TT levels, but these high levels presented no significant association with E2 levels. A significantly higher level of SHBG among TSE participants was detected in high concentrations for lead, cadmium, and mercury.

Conclusion

TSE exacerbated sex hormone imbalances when combined with high levels of metal exposure. Smoking cessation is crucial, especially in the case of high levels of occupational exposure to heavy metals.

Purpose

The present study aimed to investigate the effects of 8 weeks spirulina supplementation and circuit resistance training (CRT) on asprosin, appetite, and energy balance in men with obesity and overweight.

Methods

The study comprised a single-blind randomized controlled trial. Sixty men with obesity and overweight (BMI > 25) were selected and randomly divided into four equal groups (n = 15 each) of training plus spirulina, training plus placebo, spirulina, and placebo. The participants of the training groups performed 12 movements with 40–90% maximal repetition (three sessions per week) and the supplemental groups consumed 1000 mg of spirulina per day for 8 weeks. Asprosin, appetite using visual analog scales, calorie intake, energy expenditure, and body composition were measured before and after the intervention. To analyze the data, the paired sample t-test, analysis of covariance, Bonferroni post-hoc, and Pearson correlation tests were employed using SPSS (version 20) at a significance level of p < 0.05.

Results

After the intervention, asprosin level (P = 0.015, P = 0.015, and P = 0.020, respectively), weight (P < 0.001, P < 0.001, and P < 0.001, respectively), calorie intake (P = 0.015, P = 0.011, and P = 0.004, respectively), and hunger (P = 0.011, P = 0.015, and P = 0.015, respectively) declined in the training plus spirulina, training plus placebo, and spirulina groups (p < 0.05). In addition, energy expenditure (P = 0.012 and P = 0.015, respectively) and fullness (P = 0.015 and P = 0.011, respectively) increased in the training plus spirulina and training plus placebo groups. The mean changes of the research indicators in the training plus spirulina group were significantly more than those of the other groups (p < 0.001).

Conclusion

It was shown that 8 weeks of CRT and spirulina supplementation decreases the level of asprosin and improves appetite and energy balance in men with obesity and overweight.

Purpose

This study aimed to present recent trends in the pubertal timing of a Greek female sample.

Methods

Data were collected retrospectively from medical records of healthy females aged 6–18 years who attended a tertiary Adolescent Friendly Health Center over a 5-year period (2016–2020) and included gestational age, birth anthropometrics, and age of thelarche and/or pubarche and/or menarche, along with corresponding anthropometric, hormonal, and biochemical measurements.

Results

Data from 298 girls’ medical records were included in the analysis. Median age at menarche, thelarche, and pubarche was 12, 9, and 9 years, respectively. The mean interval between pubertal onset and menarche was 1.99 years. The mean body mass index (BMI) at menarche and thelarche was 20.99 kg/m² and 18.90 kg/m², respectively. The mean weight at menarche was 49.6 kg, whereas the mean height difference between thelarche and menarche was 19.17 cm. Among participants, 6.3% had premature menarche, while 24.0% had premature thelarche. Birth weight was moderately correlated with BMI at thelarche/pubarche (r_s=0.334, p = 0.005). Birth weight and BMI at thelarche/pubarche were not predictive of premature menarche or premature thelarche. Median (interquartile range, IQR) levels at menarche vs. thelarche were significantly higher for insulin-like growth factor-1 [358.00 (140.50) vs. 176.00 (55.00) ng/ml], follicle stimulation hormone [5.65 (3.14) vs. 3.10 (4.23) mIU/ml], testosterone [25.50 (31.00) vs. 13.00 (21.00) ng/dl], dehydroepiandrosterone sulfate [117.00 (112.50) vs. 46.40 (51.90) µg/dl], and insulin [17.40 (15.05) vs. 8.47 (4.97) µIU/ml].

Conclusion

The timing of pubertal stages in the Greek female sample studied followed the recent international downward trends. Younger age at menarche was not related to BMI.

Purpose

Neoangiogenesis is necessary for adhesion and invasiveness of endometriotic lesions in women affected by endometriosis. Vascular endothelial growth factor (VEGF) is one of the main components of angiogenesis and is part of the major pathway tissue factor (TF)-protease activated receptor-2 (PAR-2)-VEGF that leads to neoangiogenesis. Specificity protein 1 (SP1) is a transcriptional factor that has recently been studied for its crucial role in angiogenesis via a specific pathway. We hypothesize that by blocking angiogenetic pathways we can suppress endometriotic lesions. Gonadotrophin-releasing hormone-agonists (GnRH-a) are routinely used, especially preoperatively, in endometriosis. It would be of great interest to clarify which angiogenetic pathways are affected and, thereby, pave the way for further research into antiangiogenetic effects on endometriosis.

Methods

We used quantitative real-time polymerase chain reaction (qRT-PCR) to study mRNA expression levels of TF, PAR-2, VEGF, and SP1 in endometriotic tissues of women who underwent surgery for endometriosis and received GnRH-a (leuprolide acetate) preoperatively.

Results

VEGF, TF, and PAR-2 expression is significantly lower in patients who received treatment (p < 0,001) compared to those who did not, whereas SP1 expression is not altered (p = 0.779).

Conclusions

GnRH-a administration does affect some pathways of angiogenesis in endometriotic lesions, but not all of them. Therefore, supplementary treatments that affect the SP1 pathway of angiogenesis should be developed to enhance the antiangiogenetic effect of GnRH-a in patients with endometriosis.

Trial registration

Clinicaltrial.gov ID: NCT06106932.

Purpose

In patients with acromegaly, the long-term presence of elevated GH and IGF-1 levels is associated with an unfavorable cardiovascular risk profile. We aimed to assess the relationship of four-dimensional speckle tracking echocardiographic (4DSTE) measurements with growth differentiation factor-15 (GDF-15) levels and the Framingham Cardiovascular Risk Score (FRS) in patients with acromegaly.

Methods

A single-center, cross-sectional study was conducted. The study included 40 acromegaly and 32 age- and gender-matched controls. Anthropometric, biochemical, and echocardiographic assessments were performed. GDF-15 levels were measured using ELISA.

Results

In the controlled acromegaly group, global longitudinal (GLS), circumferential (GCS), area (GAS), and radial (GRS) strain measurements identified by 4DSTE were lower than those of the controls (p < 0.05). Moreover, strain parameters were lower in active acromegaly patients than in controls, but the difference was not statistically significant. The GLS was negatively correlated with age, the estimated disease duration, and FRS. Serum GDF-15 levels showed no significant difference between the acromegaly and control groups. In patients with acromegaly, serum GDF-15 levels were positively correlated with age, waist-to-hip ratio, systolic and diastolic blood pressure, FRS, fasting plasma glucose, and HbA1c, but not with strain parameters. The multiple regression analysis revealed that FRS was an independent factor associated with serum GDF-15 levels in patients with acromegaly and the overall cohort (p < 0.001).

Conclusion

Our study demonstrates that while LVEF was within normal limits, global strain parameters (GLS, GCS, GAS, and GRS) measured by using a novel imaging technique, 4DSTE, were lower in patients with acromegaly, suggesting the presence of subclinical systolic dysfunction in patients with acromegaly. GDF-15 can be a potential predictor of cardiovascular risk in patients with acromegaly.

A recently described type of neonatal diabetes mellitus is caused by mutations in the YIPF5 gene and is combined with manifestations from the central nervous system, including developmental delay, epilepsy, and microcephaly. The molecular pathophysiology behind this phenotype involves the breakdown of the endoplasmic reticulum stress response due to the loss of protein folding capacity. This results in overt diabetes present from very early in life. Herein, we describe a patient with a newly reported variant in the YIPF5 gene, who presented with short events of severe hyperglycemia, induced by the stress of common illnesses, which completely resolved after recovery. We discuss the nature of transient hyperglycemia in the context of the YIPF5 gene variant and compare this phenotype with the previously described cases.