Frontiers in Endocrinology最新文献

{"title":"Androgen receptor antagonist flutamide modulates estrogen receptor alpha expression in distinct regions of the hypospadiac rat penis.","authors":"Emilie Elmelund, Monica K Draskau, Marie Berg, Ida W Strand, Jay R Black, Marta Axelstad, Andrew J Pask, Terje Svingen","doi":"10.3389/fendo.2025.1654965","DOIUrl":"10.3389/fendo.2025.1654965","url":null,"abstract":"<p><strong>Introduction: </strong>Intrauterine exposure to endocrine disrupting chemicals (EDCs), particularly anti-androgens, has been implicated in hypospadias by disrupting fetal masculinization of the genital tubercle (GT). Other pathways, including estrogen signaling, may also contribute but remain poorly characterized, especially in rats - a key model in chemical toxicity testing. Estrogen signaling has also been linked to hypospadias in mice, raising questions about androgen-estrogen interactions in guiding GT differentiation.</p><p><strong>Methods: </strong>We induced hypospadias in male rat offspring via intrauterine exposure to the antiandrogenic drug flutamide and characterized androgen and estrogen receptor expression.</p><p><strong>Results: </strong>We observed key structural and transcriptional changes in the developing penis, including altered estrogen receptor a (ERa, Esr1) expression. Notably, beyond this established androgen-estrogen relationship in hormone-sensitive tissues, anti-androgenic exposure also induced spatial changes in Esr1 expression in specific regions of the GT.</p><p><strong>Discussion: </strong>Future toxicological testing using new approach methodologies (NAMs) should consider androgen-estrogen balance and crosstalk in reproductive tissues as a mechanism of action.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1654965"},"PeriodicalIF":4.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wet healing and Chinese medicine cupping can be used to form collateral circulation in diabetic foot artery occlusion: a case report.","authors":"Shengmei Wu, Qianqian Peng, Chunlei Tian, Junfeng Hu, Xiandi Wu, Lili Zhang, Jin Zhang","doi":"10.3389/fendo.2025.1583647","DOIUrl":"10.3389/fendo.2025.1583647","url":null,"abstract":"<p><p>This report describes a diabetic patient with a left little toe ulcer who was treated with Wet healing combined with traditional Chinese cupping. This approach successfully improved local blood circulation and facilitated wound healing. This treatment modality provides a new perspective for the comprehensive management of diabetic foot ulcers.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1583647"},"PeriodicalIF":4.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: A systematic review and evidence assessment of monogenic gene-disease relationships in human male infertility.","authors":"Qian Zhao, Huifang Peng, Jiali Chen, Hui Zhang, Yujin Ma, Hongwei Jiang","doi":"10.3389/fendo.2025.1695432","DOIUrl":"https://doi.org/10.3389/fendo.2025.1695432","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fendo.2025.1643543.].</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1695432"},"PeriodicalIF":4.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic regulation of obesity by naturally occurring compounds: mechanisms and therapeutic potential.","authors":"Mousumi Das, Unnati Yagnik, Ishita Raninga, Debashis Banerjee","doi":"10.3389/fendo.2025.1655875","DOIUrl":"10.3389/fendo.2025.1655875","url":null,"abstract":"<p><p>The global obesity epidemic continues to escalate, driving demands for safer and more effective therapeutic strategies. This review evaluates the potential of natural bioactive compounds as multi-targeted interventions for obesity management. Plant-derived polyphenols (e.g., epigallocatechin-3-gallate (EGCG), resveratrol), alkaloids (e.g., berberine), and marine carotenoids (e.g., fucoxanthin) demonstrate remarkable capacity to modulate fundamental obesity pathways through (A) suppression of adipogenesis via PPARγ and C/EBPα inhibition, (B) activation of lipolysis through hormone-sensitive lipase (HSL) stimulation and AMPK phosphorylation, (C) enhancement of thermogenesis via UCP1 upregulation, and (D) gut microbiome modulation through SCFA production. Clinical evidence supports the efficacy of selected compounds, with green tea catechins showing 4% to 5% body fat reduction and berberine demonstrating significant metabolic improvements. These natural agents offer distinct advantages over conventional drugs through their pleiotropic mechanisms and favorable safety profiles. However, bioavailability limitations and inter-individual variability present significant challenges. Innovative delivery systems, including nanoencapsulation and phospholipid complexes, show promise to enhance the therapeutic potential. The review highlights emerging strategies combining microbiome modulation with precision nutrition approaches while emphasizing the need for standardized clinical protocols. By bridging ethnopharmacological knowledge with modern scientific validation, natural compounds represent a promising avenue to develop sustainable, multi-targeted anti-obesity therapies that address both physiological and metabolic aspects of this complex disorder.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1655875"},"PeriodicalIF":4.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproductive aging in biological females: mechanisms and immediate consequences.","authors":"Yasin Ali Muhammad","doi":"10.3389/fendo.2025.1658592","DOIUrl":"10.3389/fendo.2025.1658592","url":null,"abstract":"<p><p>Reproductive aging is a dynamic, systemic process that encompasses more than the decline in ovarian function. It involves coordinated changes across neuroendocrine, immune, metabolic, and mitochondrial systems. Central to this transition is the depletion of ovarian follicles, leading to reduced estradiol and progesterone production and subsequent disruption of the hypothalamic-pituitary-gonadal (HPG) axis. This hormonal shift remodels hypothalamic signaling networks - particularly those involving kisspeptin, neurokinin B (NKB), and GABA - driving alterations in gonadotropin-releasing hormone (GnRH) pulsatility, vasomotor symptoms (VMS), and loss of reproductive cycling. Simultaneously, chronic inflammation, oxidative stress, and mitochondrial dysfunction further accelerate both ovarian and neural aging. Estrogen receptor subtypes (ERα and ERβ) play critical and region-specific roles in mediating tissue responses to hormonal withdrawal, contributing to variability in symptom expression and therapeutic outcomes. Genetic, cultural, and environmental factors - such as diet, endocrine disruptors, and APOE genotype - further influence the trajectory and severity of menopause-related changes. Emerging treatments, including neurokinin receptor antagonists and ERβ-selective modulators, offer targeted alternatives to conventional hormone therapy. This review frames menopause not as a singular endocrine endpoint but as a neuroimmune transition, highlighting the need for mechanistic insight and personalized therapeutic approaches to improve health outcomes during reproductive aging.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1658592"},"PeriodicalIF":4.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of luteolin in central precocious puberty: insights from a danazol-induced rat model.","authors":"Zhijian Zha, Enze Lei, Xiaofan Wu, Siyu Bai, Tiantian Huang, Tao Lu, Zifeng Wang, Yan Cai, Hui Li, Yao Chen, Jianzhong Liu","doi":"10.3389/fendo.2025.1666932","DOIUrl":"10.3389/fendo.2025.1666932","url":null,"abstract":"<p><strong>Background: </strong>Recently, central precocious puberty (CPP) is becoming a major public health concern worldwide due to its enhanced prevalence. Traditional Chinese medicine (TCM) compounds offer unique therapeutic advantages for treating this condition, and luteolin, a bioactive monomer compound commonly found in these herbs, has drawn increasing attention. However, the therapeutic effects of luteolin on CPP development remain unclear.</p><p><strong>Methods: </strong>A danazol-induced CPP model was established in Sprague-Dawley rats to explore the potential therapeutic effects of luteolin. Sexual development indicators, organ coefficients, gonadal histopathology, and sex hormone levels were evaluated to assess treatment outcomes. Additionally, a comprehensive approach involving network pharmacology, molecular docking, and transcriptomic analyses was used to identify luteolin-related signaling pathways and target proteins involved in CPP treatment. Finally, we carried out enzyme-linked immunosorbent assay (ELISA) and reverse transcription- quantitative polymerase chain reaction (RT-qPCR) for finding validation and exploring the underlying mechanisms.</p><p><strong>Results: </strong>In the danazol-induced CPP model, luteolin treatment significantly decreased the abundances of Estradiol (E2), luteinizing hormone serum, and follicle-stimulating hormone in sera; reduced organ coefficients and ovarian and uterine wet weights; and delayed vaginal opening. Network pharmacology and transcriptomic analyses revealed that luteolin exerted its therapeutic effects mainly by modulating immune and inflammatory pathways, including the tumor necrosis factor-α, Toll-like receptor, and IL-17 signaling pathways. Molecular docking demonstrated stable binding of luteolin to key targets such as Cxcl10, Cxcl11, Stat1, Tlr3, and Irf7. ELISA results confirmed that luteolin inhibited pro-inflammatory cytokines while promoting anti-inflammatory factors in the CPP model. Furthermore, RT-qPCR analysis revealed that luteolin enhanced Irf7 and Stat1 expression within the Toll-like receptor pathway, mainly by upregulating Tlr3, thereby enhancing the abundances of downstream effector molecules Cxcl10 and Cxcl11.</p><p><strong>Conclusion: </strong>This study is the first to determine that luteolin ameliorates CPP via the Toll-like receptor signaling pathway. These findings enhance our understanding of luteolin's pharmacological actions and support its potential role in CPP treatment.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1666932"},"PeriodicalIF":4.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: Insulin resistance in type 1 diabetes mellitus: the role of genetic factors.","authors":"Jintao Wei, Shi-Yuan Lu, Tianyue Zhang","doi":"10.3389/fendo.2025.1656453","DOIUrl":"10.3389/fendo.2025.1656453","url":null,"abstract":"<p><p>We report a 52-year-old man with autoantibody-negative type 1 diabetes (T1D) who presented with severe insulin resistance (IR). Whole-exome sequencing (WES) identified a heterozygous mutation in the IGF2BP2 gene (c.248A>G, p. Lys83Thr; rs4402960), associated with type 2 diabetes (T2D) risk. Despite intensive insulin therapy, the patient exhibited markedly elevated insulin requirements (>1.5 U/kg/day; total, 140 U/day) alongside persistent hyperglycemia. The estimated glucose disposal rate (eGDR) was 4.32 mg/kg/min, indicating significant IR. The Somogyi phenomenon was ruled out via continuous glucose monitoring (CGM), and the patient was deemed to have IR. The addition of metformin, acarbose, and dapagliflozin reduced insulin requirements and significantly improved glycemic control. This case suggests that T2D-associated genetic variants may contribute to IR in T1D and underscores the potential value of genetic testing in guiding targeted oral combination therapy.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1656453"},"PeriodicalIF":4.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoporosis self-assessment tool for Asians and calcaneal quantitative ultrasound for identifying primary osteoporosis in Taiwanese postmenopausal women.","authors":"Dung-Huan Liu, Chih-Sheng Lin, Pei-Ching Wu","doi":"10.3389/fendo.2025.1639176","DOIUrl":"10.3389/fendo.2025.1639176","url":null,"abstract":"<p><strong>Objectives: </strong>This study compares Osteoporosis Self-Assessment Tool for Asians (OSTA) and Calcaneal Quantitative Ultrasound (QUS) to detect primary osteoporosis among Taiwanese postmenopausal women and assess the consistency between both methods.</p><p><strong>Methods: </strong>8,883 postmenopausal women were selected from Taiwan Biobank. Osteoporosis was diagnosed using Dual-energy X-ray absorptiometry (DXA) with T-score≦-2.5 under WHO definition. QUS and OSTA were employed to assess osteoporosis risk, with statistical analyses including receiver operating characteristic curve (ROC) analysis, Delong's test, and McNemar's test to compare the performance of both tools. Youden's J statistic identifies the optimal cut-off values of OSTA and QUS SI. Cohen's kappa coefficient (k) and Spearman's rank correlation coefficient (r_s) assessed the correlation between OSTA, QUS, and DXA.</p><p><strong>Results: </strong>QUS outperformed OSTA with superior AUC in primary osteoporosis screening of Taiwanese postmenopausal women under WHO osteoporosis definition (AUC of QUS and OSTA are 0.737 and 0.703; p<0.05). They could independently screen and track the women at primary osteoporosis risk but not replace DXA for osteoporosis diagnosis, because they had a fair agreement of k (0.293~0.342) and a moderate correlation of r_s (0.424~0.481) with DXA. They couldn't screen and track the women at primary osteoporosis risk interchangeably because their agreement is minimal (k=0.197; r_s=0.271; p<0.05).</p><p><strong>Conclusions: </strong>QUS and OSTA are radiation-free, portable, less expensive and time-consuming, and effective screening tools for primary osteoporosis in Taiwanese postmenopausal women, with QUS being the superior method under WHO osteoporosis definition. After further age-stratified analysis for detecting primary osteoporosis in Taiwanese postmenopausal women, QUS outperformed OSTA in those aged 45 - 65, while OSTA outperformed QUS in those aged 66 - 80.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1639176"},"PeriodicalIF":4.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OvaRePred (HerTempo): an enhanced ovarian aging clock for personalized reserve assessment, endocrine age modeling, and predicting reproductive milestones across the female lifecycle.","authors":"Huiyu Xu, Guoshuang Feng, Rui Yang, Yong Han, Hongbin Chi, Rong Li","doi":"10.3389/fendo.2025.1658068","DOIUrl":"10.3389/fendo.2025.1658068","url":null,"abstract":"<p><strong>Background: </strong>Women display marked variability in ovarian reserve, which is pivotal for fertility and menopausal timing. Traditional criteria, such as Bologna and Poseidon, classify women into broad groups but do not provide individualized predictions for ovarian aging or reproductive milestones. This study aims to refine the AA model (AMH + age) to enhance clinical usability, robustness, and interpretability.</p><p><strong>Materials and methods: </strong>Single-center retrospective ART cohort (GnRH-antagonist cycles, 2017-2021). Training: 15,241 cycles (2017-2019); Testing: 14,498 cycles (2020-2021). Poor ovarian response (POR) was defined as <5 oocytes. Three logistic-regression specifications were compared: categorical (Model-0), continuous (Model-1), and polynomial (age quadratic, AMH cubic; Model-2). Discrimination (AUC), calibration, and net reclassification improvement (NRI) were evaluated. A two-parameter logistic curve was fitted to age versus predicted POR (used population-level as \"predicted DOR\") to construct an ovarian-aging trajectory and derive an interpretable \"endocrine-age\" index. Sensitivity analyses assessed cycle-day AMH variation; a community dataset was used to compare age-stratified AMH distributions.</p><p><strong>Results: </strong>While all models achieved comparable discrimination (AUC ≈ 0.85), a cubic transformation model (Model-2) demonstrated superior calibration and was selected as the final algorithm. A two-parameter logistic curve allowed translation of ovarian reserve scores into an \"endocrine age\" and enabled individualized prediction of future milestones, such as diminished reserve with ovarian score of 50 and perimenopause, the lowest ovarian reserve score in our ART population. AMH sampling on different cycle days showed only modest effects from minor fluctuations; only substantial AMH decreases significantly affected prediction accuracy. Age-stratified AMH distributions were similar between ART and community cohorts in women <40, supporting external relevance. The updated OvaRePred (HerTempo) model is cost-effective, scalable, and operationally simple.</p><p><strong>Conclusion: </strong>OvaRePred (HerTempo) delivers individualized, well-calibrated estimates of ovarian reserve and an interpretable endocrine-age index and future fertility milestone onset. While the tool can inform personalized fertility planning and may have broader public-health utility, the algorithm is trained on ART endpoints. Any projections of future reproductive milestones derived from the population ovarian-aging curve-and the fixed-interval hypothesis that underpins that curve-are hypothesis-generating and require prospective validation, particularly in non-ART cohorts with longitudinal follow-up.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1658068"},"PeriodicalIF":4.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Inflammatory markers as potential mediators on the negative association between training load and bone mineral density in adolescent competitive swimmers: ABCD-growth study.","authors":"Ricardo R Agostinete, Pedro H Narciso, Manuel João Coelho-E-Silva, Renata M Bielemann, Luis Alberto Gobbo, Bruna Camilo Turi-Lynch, Romulo Araújo Fernandes, Dimitris Vlachopoulos","doi":"10.3389/fendo.2025.1686139","DOIUrl":"https://doi.org/10.3389/fendo.2025.1686139","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fendo.2025.1602551.].</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1686139"},"PeriodicalIF":4.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}