Ovarian granulosa cells are essential to gonadotrophin-regulated estrogen production, female cycle maintenance and fertility. The epithelial Na+ channel (ENaC) is associated with female fertility; however, whether and how it plays a role in ovarian cell function(s) remained unexplored. Here, we report patch-clamp and Na+ imaging detection of ENaC expression and channel activity in both human and mouse ovarian granulosa cells, which are promoted by pituitary gonadotrophins, follicle stimulating hormone (FSH) or luteinizing hormone (LH). Cre-recombinase- and CRISPR-Cas9-based granulosa-specific knockout of ENaC α subunit (Scnn1a) in mice resulted in failed estrogen elevation at early estrus, reduced number of corpus luteum, abnormally extended estrus phase, reduced litter size and subfertility in adult female mice. Further analysis using technologies including RNA sequencing and Ca2+ imaging revealed that pharmacological inhibition, shRNA-based knockdown or the knockout of ENaC diminished spontaneous or stimulated Ca2+ oscillations, lowered the capacity of intracellular Ca2+ stores and impaired FSH/LH-stimulated transcriptome changes for estrogen production in mouse and/or human granulosa cells. Together, these results have revealed a previously undefined role of ENaC in modulating gonadotrophin signaling in granulosa cells for estrogen homeostasis and thus female fertility.

Given that the colon represents the most extensive hormone-responsive tissue in the human body, it prompts a compelling inquiry into whether the progression of its cancer is intimately linked to hormonal dynamics. Consequently, the interplay between sex steroids - a pivotal constituent of hormones - and colorectal cancer has increasingly captivated scientific interest. Upon a comprehensive review of pertinent literature both domestically and internationally, this study delineates the present landscape of three pivotal steroids - estrogen, progestin, and androgen - in the context of colorectal cancer. More specifically, this investigation probes into the potential utility of these steroids in providing therapeutic interventions, diagnostic insights, and prognostic indicators. Furthermore, this study also delves into the mechanistic pathways through which sex steroid interventions exert influence on colorectal cancer. It was discovered that the trio of sex steroid hormones partakes in an array of biological processes, thereby influencing the onset and progression of colorectal cancer. In conclusion, this study posits that a profound interconnection exists between colorectal cancer and sex steroids, suggesting that elucidating the targets of their action mechanisms could unveil novel avenues for the diagnosis and prevention of colorectal cancer.

UNASSIGNED: This study aimed to investigate the association between sex hormones and the risk of pulmonary fibrosis by conducting a meta-analysis of previously published studies.
UNASSIGNED: We executed a comprehensive search of the PubMed, Embase, Cochrane Library, and Web of Science databases to locate pertinent studies published up to April 2024. We included studies that reported the association between sex hormones and the risk of pulmonary fibrosis. Standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated using a random-effects model.
UNASSIGNED: A total of 10 articles, encompassing 1371 patients, were finally incorporated in this meta-analysis. Based on the evaluation of the included studies, it was observed that the levels of dehydroepiandrosterone sulfate (DHEA-S) (pooled SMD: -0.72, 95% CI: -1.21 to -0.24, p < 0.001), testosterone (pooled SMD: -1.25, CI: -2.39 and -0.11, p < 0.001) and estrogen (pooled SMD: -0.56, 95% CI: -0.96 to -0.15, p < 0.001) were significantly lower in patients with pulmonary fibrosis, whereas the levels of luteinizing hormone (LH) remained unaffected. Publication bias was ruled out through funnel plots.
UNASSIGNED: This meta-analysis indicates that reduced levels of DHEA-S, testosterone, estrogen may serve as potential risk factors for pulmonary fibrosis. There is a pressing need for additional studies to confirm this association and explore the underlying biological mechanisms. Clinicians should recognize the potential influence of sex hormones in the etiology of pulmonary fibrosis and consider this aspect during the patient management process.

A covalent organic framework (COF) was gown on porous silica with 1,3,5-tri(4-aminophenyl)benzene and 2,5-divinyl-1,4-phenyldiformaldehyde as monomers, and two ionic liquids were grafted to COF by a click reaction. The materials before and after the modification of ionic liquids were separately packed into solid-phase extraction columns (10 × 4.6 mm, i.d.), which were coupled with liquid chromatography to construct online analysis systems. The extraction mechanisms of polycyclic aromatic hydrocarbons, bisphenols, diphenylalkanes and benzoic acids were investigated on these materials. There were π-π, hydrogen-bond and electrostatic interactions on ionic liquid-functionalized sorbents. After the comparison among these materials, the best sorbent was used, and the analytical method was established and successfully applied to the detection of some estrogens from actual samples. For the analytical method, the detection limit was as low as 0.005 μg L-1, linear range was as wide as 0.017-10.0 μg L-1, and enrichment ratio was as high as 3635. The recoveries in actual samples were 70 %-129 %.

Salicylic esters (SEs), the widely used ultraviolet (UV) absorbers in sunscreen products, have been found to have health risks such as skin sensitization and estrogenic effects. This study aims to design SE substitutes that maintain high UV absorbance while reducing estrogenicity. Using molecular docking and Gaussian09 software for initial assessments and further application of a combination of two-dimensional and three-dimensional quantitative structure-activity relationships (2D-QSAR and 3D-QSAR, respectively) models, we designed 73 substitutes. The best-performing molecules, ethylhexyl salicylate (EHS)-5 and EHS-15, significantly reduced estrogenicity (44.54 % and 17.60 %, respectively) and enhanced UV absorbance (249.56 % and 46.94 %, respectively). Through screening for human health risks, we found that EHS-5 and EHS-15 were free from skin sensitivity and eye irritation and exhibited reduced skin permeability compared with EHS. Furthermore, the photolysis and synthetic pathways of EHS-5 and EHS-15 were deduced, demonstrating their good photodegradability and potential synthesizability. In addition, we analyzed the mechanisms underlying the changes in estrogenic effects and UV absorption properties. We identified covalent hydrogen bond basicity and acidity Propgen value for atomic molecular properties and the highest occupied molecular orbital eigenvalue as the main factors affecting the estrogenic effect and UV absorbance of SEs, respectively. This study focuses on the design and screening of SEs, exhibiting enhanced functionality, reduced health risks, and synthetic feasibility.

OBJECTIVE: As an antagonist of bone morphogenetic protein (BMP), Noggin facilitates osteolytic bone metastases from breast cancer. The present study aimed to further dissect its role in oestrogen receptor (ER) positive breast cancer.
METHODS: Noggin expression in ER positive breast cancer cell lines (MCF-7 and T-47D) was determined under conditions of oestrogen deprivation and treatment with 17-β-oestradiol (E2). Activation of Smad1/5/8 in the oestrogen-regulated Noggin was examined using recombinant human BMP7 (rhBMP7) and a BMP receptor inhibitor (LDN-193189). The influence of Noggin on cellular functions was evaluated in MCF-7 and T-47D cell lines. Responses to tamoxifen and chemotherapy drugs were determined in MCF-7 and T-47D cells with Noggin over-expression using MTT assay.
RESULTS: Noggin expression was negatively correlated with ERα in breast cancers. Noggin was up-regulated upon oestrogen deprivation, an effect that was eliminated by E2 Furthermore, increased levels of phosphorylated Smad1/5/8 were observed in the oestrogen-deprived MCF-7 and T-47D cells, which was prevented by E2 and LDN-193189, respectively. BMP7-induced Noggin expression and activation of Smad1/5/8 was also prevented by E2 and LDN-193189. Noggin over-expression resulted in an increase in the proliferation of both MCF-7 and T-47D cells. MCF-7 and T-47D cells over-expressing Noggin exhibited a good tolerance to tamoxifen (TAM), DTX, and 5-FU, but the percentage of viable cells was higher compared with the controls.
CONCLUSIONS: Noggin expression can be repressed by oestrogen through inference with the BMP/Smad signalling. Over-expression of Noggin promotes the proliferation of MCF-7 and T-47D cells, contributing to drug resistance.

OBJECTIVE: To investigate the impact of age, various hormonal levels, and biochemical markers on penile cavernous body vascular function in patients with erectile dysfunction (ED). Me-thods: A retrospective analysis of clinical data from male patients with ED who underwent color duplex Doppler ultrasonography (CDDU) and intracavernosal injection test (ICI) at the Reproductive Medicine Center of Peking University Third Hospital from January 2020 to August 2023. Data were managed and processed using SPSS 29.0, and a multivariable Logistic regression analysis was conducted.
RESULTS: A total of 700 ED patients were included, with 380 showing negative ICI results and 320 positive. In the study, 84 patients had a peak systolic velocity (PSV) < 25 cm/s, while 616 had PSV≥25 cm/s; 202 patients had end-diastolic velocity (EDV)>5 cm/s, and 498 had EDV≤5 cm/s. 264 patients had abnormal PSV and/or EDV results, and 436 had normal results for both. Patients with vascular ED had significantly lower estrogen levels (t=-3.546, P < 0.001), lower testosterone levels (t=-2.089, P=0.037), and a higher rate of hyperglycemia (χ2=12.772, P=0.002) compared with those with non-vascular ED. The patients with arterial ED were older (t=3.953, P < 0.001), had a higher rate of hyperglycemia (χ2=9.518, P=0.009), and a higher estrogen/testosterone ratio (t=2.330, P=0.020) compared with those with non-arterial ED. The patients with mixed arteriovenous ED had higher age (t=3.567, P < 0.001), lower testosterone levels (t=-2.288, P=0.022), a higher rate of hyperglycemia (χ2=12.877, P=0.002), and a larger estrogen/testosterone ratio (t=2.096, P=0.037) compared with those with normal findings. Multifactorial Logistic regression analysis indicated that higher levels of estrogen were a protective factor for vascular ED (OR=1.009, 95%CI: 1.004-1.014), and glucose≥7.0 mmol/L was a risk factor (OR=0.381, 95%CI: 0.219-0.661). Older age was a risk factor for arterial ED (OR=0.960, 95%CI: 0.938-0.982). Additionally, older age (OR=0.976, 95%CI: 0.958-0.993) and glucose levels of 5.6-6.9 mmol/L (OR=0.591, 95%CI: 0.399-0.876) were also risk factors for mixed arterio-venous ED.
CONCLUSIONS: Hyperglycemia and aging may impair penile cavernous body vascular function, while higher levels of estrogen may have a protective effect on it.

A novel magnetic dispersive solid phase extraction (MDSPE) procedure based on the deep eutectic solvent (DES) modified magnetic graphene oxide/metal organic frameworks nanocomposites (MGO@ZIF-8@DES) was established and used for the efficient enrichment of estradiol, estrone, and diethylstilbestrol in cosmetics (toner, lotion, and cream) for the first time. Then, the three estrogens were separated and determined by UHPLC-UV analysis method. In order to study the features and morphology of the synthesized adsorbents, various techniques such as FT-IR, SEM, and VSM measurements were executed. The MGO@ZIF-8@DES nanocomposites combine the advantages of high adsorption capacity, adequate stability in aqueous solution, and convenient separation from the sample solution. To achieve high extraction recoveries, the Box-Behnken design and single factor experiment were applied in the experimental design. Under the optimum conditions, the method detection limits for three estrogens were 20-30 ng g-1. This approach showed a good correlation coefficient (r more than 0.9998) and reasonable linearity in the range 70-10000 ng g-1. The relative standard deviations for intra-day and inter-day were beneath 7.5% and 8.9%, respectively. The developed MDSPE-UHPLC-UV method was successfully used to determine  three estrogens in cosmetics, and acceptable recoveries in the intervals of 83.5-95.9% were obtained. Finally, three estrogens were not detected in some cosmetic samples. In addition, the Complex GAPI tool was used to evaluate the greenness of the developed pretreatment method. The developed MDSPE-UHPLC-UV method is sensitive, accurate, rapid, and eco-friendly, which provides a promising strategy for determining hormones in different complex samples.

Estrogen plays a pivotal role in the early stage of sex differentiation in teleost. However, the underlying mechanisms of estrogen-induced feminization process are still needed for further clarification. Here, the comparative analysis of whole-transcriptome RNA sequencing was conducted between 17beta-Estradiol induced feminized XY (E-XY) gonads and control gonads (C) in Takifugu rubripes. A total of 57 miRNAs, 65 lncRNAs, and 4 circRNAs were found to be expressed at lower levels in control-XY (C-XY) than that in control-XX (C-XX), and were up-regulated in XY during E2-induced feminization process. The expression levels of 24 miRNAs, and 55 lncRNAs were higher in C-XY than that in C-XX, and were down-regulated in E2-treated XY. Furthermore, a correlation analysis was performed between miRNA-seq and mRNA-seq data. In C-XX/C-XY, 114 differential expression (DE) miRNAs were predicted to target to 904 differential expression genes (DEGs), while in C-XY/E-XY, 226 DEmiRNAs were predicted to target to 2,048 DEGs. In C-XX/C-XY, and C-XY/E-XY, KEGG pathway enrichment analysis showed that those targeted genes were mainly enriched in MAPK signaling, calcium signaling, steroid hormone biosynthesis and ovarian steroidogenesis pathway. Additionally, the competitive endogenous RNA (ceRNA) regulatory network was constructed by 24 miRNAs, 21 lncRNAs, 4 circRNAs and 5 key sex-related genes. These findings suggested that the expression of critical genes in sex differentiation were altered in E2-treated XY T. rubripes may via the lncRNA-miRNA-mRNA regulation network to facilitate the differentiation and maintenance of ovaries. Our results provide a new insight into the comprehensive understanding of the effects of estrogen signaling pathways on sex differentiation in teleost gonads.

Heart rate variability (HRV) is a non-invasive quantitative measure of cardiac autonomic nervous activity. Due to the increase of age and the decrease of estrogen level in perimenopausal and postmenopausal women, the cardiac autonomic nervous function is abnormal, increasing the risk of cardiovascular disease. Proper exercise can increase estrogen levels, improve cardiovascular health, regulate cardiac autonomic nervous activity, and reduce the risk of cardiovascular disease. Low-moderate intensity aerobic exercise, resistance exercise, aerobic combined resistance exercise and mind-body exercise have positive effects on HRV in perimenopausal and postmenopausal women. Therefore, summarizing the effects of different exercise modes on HRV in perimenopausal and postmenopausal women, as well as the mechanism of exercise training improvement on HRV, so as to adopt better exercise strategies to improve HRV of perimenopausal and postmenopausal women, and thus reduce the risk of cardiovascular diseases and improve the health level and quality of life of perimenopausal and postmenopausal women.
心率变异性(heart rate variability，HRV)可以无创定量评估心脏自主神经活动。围绝经期和绝经后妇女由于年龄的增加和体内雌激素水平的降低，导致其心脏自主神经功能异常，心血管疾病的患病风险增加。而适当的运动可以提高雌激素水平，改善心血管健康水平，调节心脏自主神经活动，降低心血管疾病的发生风险。中低强度的有氧运动、抗阻运动、有氧结合抗阻运动和身心运动可对围绝经期和绝经后妇女HRV产生积极影响。总结不同运动方式对围绝经期和绝经后妇女HRV的影响以及运动改善HRV的机制，可为采取更佳的运动策略以改善围绝经期和绝经后妇女HRV提供依据，进而降低心血管疾病的患病风险，提高围绝经期和绝经后妇女的健康水平和生活质量。.