Hormone Molecular Biology and Clinical Investigation最新文献

{"title":"Assessment of circulating xenin as a potential metabolic biomarker in active smokers.","authors":"Mustafa Onmaz, Ahmet E Hatır, Duygu E Onmaz","doi":"10.1515/hmbci-2026-0037","DOIUrl":"https://doi.org/10.1515/hmbci-2026-0037","url":null,"abstract":"<p><strong>Objectives: </strong>Xenin regulates appetite, motility, and metabolic homeostasis. As the link between smoking and xenin has not yet been sufficiently investigated, this study compared serum levels between smokers and non-smokers and evaluated their associations with metabolic, hematological, and tobacco-related parameters.</p><p><strong>Methods: </strong>Utilizing a cross-sectional case-control framework, the present study evaluated a group of 128 subjects, comprising 66 smokers and 62 non-smokers. Serum xenin levels and clinical, metabolic, lipid, and hematological parameters were compared between groups. Subgroup analyses were performed according to sex, body mass index (BMI), and HOMA-IR categories. Correlation analyses were conducted to evaluate the associations of xenin with smoking exposure, nicotine dependence, and laboratory variables.</p><p><strong>Results: </strong>Circulating xenin concentrations exhibited a significant elevation in the smoking group relative to non-smokers (p<0.001), and this difference persisted across the normal-weight (p=0.001), overweight (p=0.002), and obese (p<0.001) BMI categories, as well as in the HOMA-IR <2.5 (p=0.043) and HOMA-IR ≥2.5 (p<0.001) subgroups. In addition, xenin levels were positively correlated with pack-years, Fagerström score, HOMA-IR, and glucose (all p<0.05). Although xenin levels tended to increase with greater smoking exposure, the overall difference among smoking exposure groups was not statistically significant (p=0.151).</p><p><strong>Conclusions: </strong>Serum xenin levels were significantly higher in smokers than in non-smokers, and this difference remained significant across BMI and HOMA-IR subgroups. These findings suggest that circulating xenin may be associated with smoking-related metabolic and neuroendocrine alterations and may have potential as a candidate biomarker. Further prospective studies are needed to validate its clinical relevance.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TSHR gene expression and mitochondrial-cardiac interactions as emerging predictors of cardiovascular risk in early thyroid dysfunction.","authors":"Manjusha Kottola, Desigamani Kanniyappan, Damodaran Boopathi, Jeyapal Vidhyadharan, Renjitha Ramachandran, Roshma Retnakaran, Joby Paruthiparayil Jose, Jisha Anjali Madhavan Pillai, Dinesh Roy Divakaran","doi":"10.1515/hmbci-2026-0026","DOIUrl":"https://doi.org/10.1515/hmbci-2026-0026","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate biochemical, hormonal, genetic, and mitochondrial alterations associated with cardiovascular risk in SCH, emphasizing the interplay between NT-proBNP, succinate dehydrogenase (SDH) complex activity, and thyroid-stimulating hormone receptor (TSHR) gene expression.</p><p><strong>Methods: </strong>A case-control study was conducted involving SCH patients and age-matched euthyroid controls. Serum thyroid profiles, NT-proBNP, and SDH complex activity were quantified by standard assays, and TSHR gene expression was measured using RT-PCR. Receiver operating characteristic (ROC) analyses assessed diagnostic performance, and multiple linear regression identified independent predictors of TSHR expression.</p><p><strong>Results: </strong>Compared with controls, SCH cases showed significantly higher TSH and NT-proBNP levels, reduced SDH complex activity, and upregulated TSHR gene expression (p<0.05). ROC analysis demonstrated excellent diagnostic accuracy for NT-proBNP, SDHA, and TSHR expression. After adjustment for confounders, SDH complex activity remained the only independent predictor of TSHR expression, whereas NT-proBNP lost independent significance, suggesting an indirect or interaction-mediated effect.</p><p><strong>Conclusions: </strong>SDHA serves as a robust independent predictor of cardiovascular risk in SCH, highlighting mitochondrial dysfunction in thyroid receptor regulation. NT-proBNP showed predictive potential but not independent significance, indicating secondary modulation by hormonal or metabolic factors. Larger longitudinal studies are warranted for validation.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular pathways of inflammation in prediabetes.","authors":"Beverley Adams-Huet, Ishwarlal Jialal","doi":"10.1515/hmbci-2026-0025","DOIUrl":"10.1515/hmbci-2026-0025","url":null,"abstract":"<p><strong>Objectives: </strong>Prediabetes is a major international problem that confers an increased risk for T2DM and CVD. There is scantly data on the role of cellular inflammatory pathways in prediabetes. We investigated the relationship between prediabetes and cellular biomarkers of inflammation.</p><p><strong>Methods: </strong>This study included patients with prediabetes (n=47) and controls (n=55). Fasting blood samples were obtained for circulating biomarkers and monocyte isolation. Also subcutaneous adipose tissue biopsies were performed in a subgroup.</p><p><strong>Results: </strong>Circulating biomarkers of inflammation were increased with prediabetes even following age adjustment. In monocytes there was a significant increase in TLR2 and its downstream signaling pathways including NFkB and P38 MAPkinase activity. In adipose tissue NLRP-3 inflammasome activity quantified by caspase1 was significantly increased whilst there was a trend to significance for IL-1beta. Also mast cells in AT were significantly increased.</p><p><strong>Conclusions: </strong>In patients with prediabetes we present novel data supporting increased cellular pathways of inflammation in both monocytes and adipose tissue further underscoring the pro-inflammatory state of prediabetes as an important potential mechanism for the increase risk for T2DM and CVD.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrine dysfunction in transfusion-dependent and non-transfusion-dependent beta-thalassemia: a systematic review and meta-analysis.","authors":"Prabhat, Akash Bansal, Jagriti, Vijaya Lakshmi, Devajit Sarmah","doi":"10.1515/hmbci-2026-0019","DOIUrl":"https://doi.org/10.1515/hmbci-2026-0019","url":null,"abstract":"<p><strong>Introduction: </strong>To systematically compare adrenal, thyroid, and growth hormone axes between transfusion-dependent (TDT) and non-transfusion-dependent (NTDT) beta-thalassemia patients, and to quantify differences in hormone levels and prevalence of endocrine abnormalities.</p><p><strong>Content: </strong>A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines. MEDLINE (PubMed), Embase, and Scopus were searched from inception to 2024. Studies reporting quantitative hormone data stratified by transfusion status were included. Primary outcomes were morning serum cortisol, thyroid hormones (TSH, T4), and growth hormone or IGF-1 levels. Random-effects meta-analysis was performed, and risk of bias was assessed using the Joanna Briggs Institute checklist.</p><p><strong>Summary: </strong>Out of 217 records, four studies (n=427; 209 TDT, 218 NTDT) were included. Three studies were pooled for cortisol analysis, showing no significant difference between groups (SMD 0.27; 95 % CI -1.25 to 1.79; I²=91.6 %). Despite comparable basal cortisol levels, adrenal insufficiency prevalence was high (38-44 %) in both groups based on dynamic testing. Thyroid dysfunction was more frequent in TDT patients, though heterogeneity limited the meta-analysis. One paediatric study reported lower IGF-1 levels and higher growth impairment in TDT. Serum ferritin levels were consistently higher in TDT cohorts. Risk of bias was moderate to high in half of the studies.</p><p><strong>Outlook: </strong>Basal cortisol levels were similar between TDT and NTDT patients; however, significant endocrine morbidity persists, particularly in TDT. These findings emphasize the need for comprehensive endocrine evaluation beyond basal hormone measurements across all thalassemia patients.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of HLA-G expression, hormonal profiles, and inflammatory markers in women with recurrent pregnancy loss.","authors":"Simi Nadarajan, Arumugam Suresh, Dinesh Roy Divakaran, Natrajan Muninathan, Venugopal Gopikrishnan, Jeena Jose, Aswathi Palakkattu Veetil","doi":"10.1515/hmbci-2026-0014","DOIUrl":"10.1515/hmbci-2026-0014","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate the role of Human Leukocyte Antigen-G (HLA-G) gene expression, inflammatory cytokines, and hormonal profiles in the pathogenesis of recurrent pregnancy loss (RPL) and to assess their potential as diagnostic and predictive markers.</p><p><strong>Methods: </strong>A case-control study was conducted involving 240 women, including 120 with clinically confirmed RPL and 120 fertile controls. Serum levels of CRP (C-reactive protein) and IL-6 (interleukin-6) were measured using enzyme-linked immunosorbent assay (ELISA). Hormonal parameters, including thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), were analyzed using chemiluminescence immunoassays (CLIA). HLA-G gene expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analyses included t-tests, receiver operating characteristic (ROC) curve analysis, and logistic regression to identify independent predictors.</p><p><strong>Results: </strong>RPL cases showed significantly higher levels of TSH, FSH, CRP, and IL-6 and markedly lower HLA-G gene expression compared with controls (p < 0.001). CRP showed the highest diagnostic accuracy (AUC = 0.997), followed by HLA-G (AUC = 0.938) and IL-6 (AUC = 0.896). Logistic regression identified IL-6, FSH, TSH, and HLA-G as independent predictors of RPL.</p><p><strong>Conclusions: </strong>The findings highlight the interplay between immune dysfunction, hormonal imbalance, and reduced HLA-G expression in RPL. These markers may help in the early identification and risk assessment of RPL, with HLA-G showing potential for further investigation as a therapeutic target.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":"101-108"},"PeriodicalIF":1.9,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual effects of progesterone on HaCaT human keratinocytes: apoptosis induction and suppression of oxidative stress and TLR2 expression with potential implications for hyperplastic skin disorders.","authors":"Seyedeh Sindokht Hosseini, Elham Akbari, Somaye Karimi, Mohammad Fereidouni, Gholamreza Anani-Sarab, Nasrin Sereshki, Mitra Rafiee","doi":"10.1515/hmbci-2026-0013","DOIUrl":"10.1515/hmbci-2026-0013","url":null,"abstract":"<p><strong>Objectives: </strong>Hyperplastic skin disorders such as psoriasis are characterized by excessive keratinocyte proliferation, impaired apoptosis, oxidative stress, and sustained activation of innate immune pathways. While conventional treatment primarily targets these mechanisms, emerging interest focuses on the immunomodulatory roles of sex hormones such as progesterone (P4). Clinical observations that psoriasis symptoms often improve during pregnancy, when P4 levels increase, further support this hypothesis. However, the direct effects of P4 on keratinocyte behavior and related molecular pathways remain poorly understood. The study aimed to evaluate the impact of P4 on key pathological features of keratinocytes using the HaCaT cell line as an <i>in vitro</i> model.</p><p><strong>Methods: </strong>HaCaT cells were cultured in DMEM medium with 10 % FBS and 1 % penicillin/streptomycin. Cells treated with various concentrations of P4, as well as untreated controls, were incubated at 37 °C incubator with 5 % CO₂ for 1-3 days. Following treatment, cell viability, apoptosis, oxidative stress, and Toll-like receptor 2 (TLR2) expression were assessed using MTT assay and flow cytometry.</p><p><strong>Results: </strong>P4 significantly reduces keratinocyte proliferation and promotes apoptosis. Moreover, it also decreased intracellular reactive oxygen species (ROS) levels and downregulated TLR2 surface expression (p value≤0.05).</p><p><strong>Conclusions: </strong>These findings highlight the multifaceted ability of P4 to modulate keratinocyte biology by regulating proliferation, apoptosis, oxidative balance, and inflammatory signaling. Interestingly, these effects occurred despite the absence of specific membrane P4 receptors, suggesting alternative pathways may mediate its actions. Further investigations under inflammatory conditions and <i>in vivo</i> models are warranted to validate these results and explore potential therapeutic applications.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectrum of disorders of sexual development in Duhok, Iraq (2012-2022): molecular and clinical profile with surgical outcomes.","authors":"Mohammed Aldabbagh, Qadir Salih, Hazhmat Ali, Shelan Rasool","doi":"10.1515/hmbci-2026-0046","DOIUrl":"10.1515/hmbci-2026-0046","url":null,"abstract":"<p><strong>Objectives: </strong>This study investigates the spectrum of disorders of sexual development (DSD) cases documented in Duhok Governorate, Iraq, from 2012 to 2022. It further characterizes the molecular and clinical profiles of treated patients and evaluates their surgical outcomes.</p><p><strong>Methods: </strong>Data were retrospectively collected from 52 DSD pediatric patients (0-18 years). Each patient underwent a comprehensive physical assessment and a diagnostic workup, including chromosomal analysis (karyotyping) and hormonal profiling. Endoscopic assessment was performed when further anatomical clarification was required. A multidisciplinary team evaluated each case to reach consensus on diagnosis, gender assignment, and management plans. Surgical interventions and non-surgical management, such as hormone replacement therapy, were provided as indicated. Postoperative follow-up protocols were implemented to monitor surgical outcomes.</p><p><strong>Results: </strong>The prevalence of DSD was 28.7 per 10,000. Most cases (48.1 %) were diagnosed with congenital adrenal hyperplasia (CAH), followed by partial androgen insensitivity syndrome (PAIS, 23.1 %), complete androgen insensitivity syndrome (CAIS, 7.6 %), Persistent Müllerian Duct Syndrome (PMDS, 5.8 %), and Turner syndrome (1.9 %). The XX DSD group exhibited a higher proportion of CAH diagnoses, while the XY group had higher proportions of PAIS, CAIS, and PMDS. This difference was statistically significant (phi=0.715, p=0.003).</p><p><strong>Conclusions: </strong>This decade-long pediatric surgical experience in Duhok demonstrates that pediatricians and surgeons can accurately diagnose DSD categories, deliver care aligned with international standards, and achieve improved surgical outcomes. Future research should prioritize standardized psychosocial assessments and sustained investment to translate genomic advances into equitable, evidence-based care worldwide.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-trimester serum SHBG and vaspin as combined biomarkers for predicting gestational diabetes mellitus: a case-control accuracy study.","authors":"Zhijie Li, Peng Yue, Jing Zhao, Cheng Kang, Xixian Wang","doi":"10.1515/hmbci-2026-0012","DOIUrl":"10.1515/hmbci-2026-0012","url":null,"abstract":"<p><strong>Objectives: </strong>Early prediction of gestational diabetes mellitus (GDM) is crucial. This study evaluated the combined predictive value of sex hormone-binding globulin (SHBG) and visceral adipose tissue-derived serine protease inhibitor (vaspin) in early pregnancy for GDM.</p><p><strong>Methods: </strong>A retrospective case-control study was conducted involving 50 pregnant women diagnosed with GDM (GDM group) and 50 with normal glucose tolerance (control group) from January to December 2022 at Beijing Aerospace General Hospital. Fasting venous blood was collected at 8-13⁺⁶ weeks of gestation. Serum levels of SHBG and vaspin were measured by enzyme-linked immunosorbent assay (ELISA). Clinical data including age, body mass index (BMI), parity, family history of diabetes, gestational age, amniotic fluid index (AFI), mode of delivery, and neonatal birth weight were compared between groups. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the predictive value of individual and combined biomarkers.</p><p><strong>Results: </strong>Pre-pregnancy BMI, cesarean section rate, and neonatal birth weight were significantly higher in the GDM group. Serum SHBG levels were significantly lower (392.26 ± 46.34 vs. 454.49 ± 31.66 nmol/mL, p<0.001), and vaspin levels were significantly higher (3.04 ± 0.47 vs. 2.54 ± 0.36 ng/mL, p<0.001) in GDM. The combined model of SHBG and vaspin showed superior predictive performance (AUC=0.934, accuracy=91.0 %, sensitivity=87.2 %, specificity=94.9 %) compared to either biomarker alone.</p><p><strong>Conclusions: </strong>The combined measurement of serum SHBG and vaspin in early pregnancy suggests a potentially useful predictive performance for GDM. While limited by the relatively small sample size and the research-use-only nature of the vaspin assay, this dual-biomarker approach warrants further validation in larger studies before its clinical applicability can be fully established.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":"109-114"},"PeriodicalIF":1.9,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of APOE gene expression with thyroid dysfunction, inflammation, and nitrosative stress in cardiometabolic syndrome: a case-control study.","authors":"Thahira Abdulla, Thirumal Kumar D, Jaiganesh Inbanathan, Jeyapal Vidhyadharan, Midhun Thazhissery Mohanan, Swathi Thoduvayil, Roshma Retnakaran, Harisree Panikkaveedu Haridas, Simi Skariah, Dinesh Roy Divakaran","doi":"10.1515/hmbci-2026-0007","DOIUrl":"10.1515/hmbci-2026-0007","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to examine the association of thyroid-stimulating hormone (TSH), interleukin-6 (IL-6), and 3-nitrotyrosine (3-NT) with ApoE gene expression and to evaluate their diagnostic utility in CMS.</p><p><strong>Methods: </strong>This case-control study compared hormonal, inflammatory, oxidative stress, and gene expression markers between CMS cases and healthy controls. Group differences were analyzed using non-parametric tests. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis, and relationships among variables were assessed using correlation and multivariable logistic regression models.</p><p><strong>Results: </strong>CMS cases showed significantly higher levels of TSH, IL-6, 3-NT, and ApoE gene expression compared with controls. TSH demonstrated modest diagnostic accuracy (AUC=0.740), whereas 3-NT exhibited excellent discriminative performance (AUC=0.963). IL-6 also showed good diagnostic accuracy. ApoE gene expression demonstrated strong diagnostic performance and was positively correlated with TSH, 3-NT, and IL-6, with the strongest association observed for IL-6. Multivariable regression analysis confirmed that elevated TSH, IL-6, and 3-NT were independently associated with CMS status.</p><p><strong>Conclusions: </strong>CMS is characterized by the convergence of thyroid dysregulation, inflammation, oxidative stress, and increased ApoE gene expression. These findings highlight a coordinated molecular network underlying CMS and support the integration of molecular and inflammatory biomarkers into cardiometabolic risk assessment. Larger longitudinal studies are required to confirm these observations.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":"91-100"},"PeriodicalIF":1.9,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen receptor signaling without estrogen: molecular insights into hormone resistance.","authors":"Gunvanti Rathod, Pragnesh Parmar","doi":"10.1515/hmbci-2025-0086","DOIUrl":"10.1515/hmbci-2025-0086","url":null,"abstract":"<p><strong>Objectives: </strong>Estrogen receptor alpha (ERα) is thought to be a ligand-dependent transcription factor. Increasing number of data suggest that ERα is able to retain its transcriptional activity without stimulation by estrogen and therefore contributes to development of endocrine resistance in hormone receptor-positive cancers. The objective of this paper is to overview molecular mechanisms of ligand-independent activation of ERα and to address the clinical significance of these mechanisms.</p><p><strong>Methods: </strong>A detailed literature review of recent experimental, translational and clinical studies has been performed with the aim of exploring molecular mechanisms of ligand-independent ERα activation, clinical significance of these mechanisms, and their application to molecular diagnostics and targeted therapy.</p><p><strong>Results: </strong>There are several ways of maintaining transcriptional activity of ERα in the absence of estrogen ligand. They include ESR1 mutations and gene fusions, alterations in signaling pathways involving growth factor receptors, abnormalities in regulation by co-regulators, epigenetic rewiring, and post-translational modifications. These changes contribute to endocrine resistance and might explain the discordance between expression of ER determined by immunohistochemical staining and clinical response to endocrine therapy.</p><p><strong>Conclusion: </strong>The recognition of signaling by ERα that is not ligand-dependent will lead to an expansion of knowledge about the estrogen receptor and the shortcomings of depending only on immunohistochemical ER status for decision making in treatment. It might be beneficial for the prediction of patients' sensitivity to endocrine treatment by adding molecular biomarkers related to the activity of the ERα.</p>","PeriodicalId":13224,"journal":{"name":"Hormone Molecular Biology and Clinical Investigation","volume":" ","pages":"87-90"},"PeriodicalIF":1.9,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}