Journal of Steroid Biochemistry and Molecular Biology最新文献

{"title":"Anabolic-androgenic steroids at supraphysiological doses: Cardiovascular impacts and pathophysiological mechanisms","authors":"Higor Souza Nascimento ,&nbsp;Marcella Guerra Corrêa ,&nbsp;Odonilton Lima Lemos ,&nbsp;Hernando Nascimento Lima ,&nbsp;Liliany Souza de Brito Amaral","doi":"10.1016/j.jsbmb.2026.106938","DOIUrl":"10.1016/j.jsbmb.2026.106938","url":null,"abstract":"<div><div>This narrative review explores the cardiovascular risks associated with the non-therapeutic use of anabolic-androgenic steroids (AAS) at supraphysiological doses. Initially indicated for clinical conditions like hypogonadism and anemia, AAS are increasingly misused for aesthetic and performance enhancement, often at doses far exceeding therapeutic recommendations. Through a literature review of 34 studies selected from PubMed (2015–2025), the review analyzes the molecular mechanisms and cardiovascular consequences of high-dose AAS use. Genomic and non-genomic pathways, along with modulation of the IGF-1 axis, underlie alterations in gene expression and cellular metabolism that lead to myocardial remodeling, hypertension, dyslipidemia, thrombosis, endothelial dysfunction, and systemic inflammation. These effects are further intensified by behavioral factors such as polypharmacy and substance abuse. Despite ethical limitations on clinical trials with supraphysiological doses, experimental and epidemiological data consistently suggest that excessive AAS use significantly elevates the risk of adverse cardiovascular events. This work highlights the urgent need for public health policies, educational initiatives, and longitudinal studies to assess real-world use patterns and mitigate harms associated with AAS abuse.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"258 ","pages":"Article 106938"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of repeated administration of oxandrolone in female wistar rats undergoing strength training","authors":"Estéfani Marin ,&nbsp;Nice Vilar Torres ,&nbsp;Maria Manoela Rezende Severo ,&nbsp;Nicolas Guimarães Santos ,&nbsp;Shanda Cattani ,&nbsp;Luciana Grazziotin Rossato-Grando ,&nbsp;Eliane Dallegrave ,&nbsp;Mirna Bainy Leal ,&nbsp;Rosane Gomez ,&nbsp;Solange Cristina Garcia ,&nbsp;Marcelo Dutra Arbo ,&nbsp;Bruno Dutra Arbo","doi":"10.1016/j.jsbmb.2026.106949","DOIUrl":"10.1016/j.jsbmb.2026.106949","url":null,"abstract":"<div><div>Anabolic androgenic steroids are synthetic derivatives of testosterone that mimic its actions in various tissues. Due to its strong anabolic activity, weak androgenic effects, and resistance to hepatic metabolism, oxandrolone is one of the most commonly used anabolic steroids among female athletes. This study aimed to evaluate the anabolic effects of oxandrolone and its toxicological profile in female rats subjected to a strength training protocol. A total of 24 female Wistar rats (60 days old) were randomly assigned to receive oxandrolone (1.77 mg/kg/day) or its vehicle (corn oil) (n = 12 per group) via daily gavage for 28 days. The exercise protocol consisted of six climbs on an inclined ladder, with two climbs per workload (50 %, 75 %, and 100 % of each animal’s maximum load) performed three times per week. Investigators remained blinded throughout experimentation and data analysis. Oxandrolone did not significantly affect body weight gain, relative organ and muscle mass, or muscle strength. However, it altered mean corpuscular volume, eosinophil count, and urea levels. Additionally, liver TBARS levels increased, while no changes were observed in plasma lipid peroxidation, antioxidant enzyme activity, total non-protein thiol levels, or mitochondrial respiratory chain complex activity. Histopathological analysis revealed oxandrolone-induced damage to cardiac and skeletal muscle, along with structural alterations in the spleen and adrenal gland. Given its limited effect on muscle strength, along with histopathological changes and increased liver lipoperoxidation, these findings raise concerns about oxandrolone use in healthy individuals seeking aesthetic or athletic benefits.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"258 ","pages":"Article 106949"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of dehydroepiandrosterone in early osteoarthritis: Modulating cartilage ECM stiffness through LOX-RhoA/ROCK/MLC signalling – An in vivo study","authors":"Kai Huang ,&nbsp;Haili Cai ,&nbsp;Cheng Jiang ,&nbsp;Chunwei Zheng","doi":"10.1016/j.jsbmb.2026.106936","DOIUrl":"10.1016/j.jsbmb.2026.106936","url":null,"abstract":"<div><div>Osteoarthritis (OA) is characterized by progressive cartilage degeneration and extracellular matrix (ECM) stiffening, yet effective disease-modifying therapies remain limited. This study evaluated the chondroprotective effect of dehydroepiandrosterone (DHEA) in early OA and elucidated its underlying mechanisms. Using rabbit and mouse models, we demonstrated that intra-articular DHEA administration attenuated cartilage damage, reduced catabolic enzyme expression, and preserved ECM elasticity. Mechanistically, DHEA downregulated lysyl oxidase (LOX), suppressed activation of the RhoA/ROCK/MLC signaling cascade, and thereby mitigated ECM stiffening. The protective effects were partly dependent on LOX inhibition, suggesting a dual regulatory mechanism. These findings identify DHEA as a potential disease-modifying agent that targets LOX-RhoA/ROCK/MLC signaling to maintain cartilage homeostasis in early OA, warranting further clinical investigation.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"258 ","pages":"Article 106936"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum steroid profiling by LC-MS/MS in distinguishing adrenocortical carcinoma from other indeterminate adrenal masses","authors":"Archana Rao ,&nbsp;Aditya Phadte ,&nbsp;Anuj Ban ,&nbsp;Saba Samad Memon ,&nbsp;Manjiri Karlekar ,&nbsp;Anurag Ranjan Lila ,&nbsp;Vijaya Sarathi ,&nbsp;Nimmi Kansal ,&nbsp;Rohit Barnabas ,&nbsp;Padma Vikram Badhe ,&nbsp;Gwendolyn Fernandes ,&nbsp;Sameer Rege ,&nbsp;Gagan Prakash ,&nbsp;Santosh Menon ,&nbsp;Nalini Shah ,&nbsp;Tushar Bandgar","doi":"10.1016/j.jsbmb.2026.106937","DOIUrl":"10.1016/j.jsbmb.2026.106937","url":null,"abstract":"<div><div>For an adrenal incidentaloma with indeterminate imaging characteristics, urine multisteroid profiling is suggested for diagnosing adrenocortical carcinoma (ACC). Data on the utility of serum steroid metabolomics in this context is limited to a few studies. Here, we present data of 62 adult patients with indeterminate unilateral adrenal masses (size ≥ 3 cm and basal attenuation ≥10HU) where baseline serum liquid chromatography-tandem mass spectrometry (LC-MS/MS) multisteroid profiling was available. Logistic regression was used to identify the key steroid signature for differentiating ACC from other non-ACC adrenal masses. Among 62 patients (median age: 41 years, 31 males), 37 (59.6 %) had ACC. The non-ACC cohort (n = 25) comprised pheochromocytoma (n = 9), adrenocortical adenoma (n = 8), metastases (n = 4), schwannoma (n = 2), ganglioneuroma (n = 1), and lymphoma (n = 1). Tumour size was significantly larger in the ACC cohort (9.9 vs 7.0 cm; p &lt; 0.001) than the non-ACC cohort. Nine of 13 steroids were significantly elevated in ACC: 11-deoxycorticosterone (DOC), 17-hydroxyprogesterone (17OHP), 11-deoxycortisol (S), cortisone (E), androstenedione (A4), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulphate (DHEAS) in both sexes, as well as testosterone (T) in females and progesterone (P4) in males. After excluding sex-dependent steroids, univariate analysis yielded six significant steroids (17OHP, S, E, A4, DHEA, and DHEAS). A multivariate logistic regression model with backward elimination identified A4, S, and DHEAS as the best discriminators (AUC:0.923), with a cutoff of 0.52 yielding 83.8 % sensitivity and 96 % specificity for diagnosing ACC. Our study results suggest serum LC–MS/MS profiling of three steroids (A4, S, and DHEAS) provides a non-invasive approach to distinguish ACC from other indeterminate adrenal masses.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"258 ","pages":"Article 106937"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased TGF-β signaling during antiestrogen therapy in triple-negative breast cancer cells","authors":"Nandani Dharwal,&nbsp;Deepshikha Rathore,&nbsp;Nirali Shukla,&nbsp;Heena V. Dave","doi":"10.1016/j.jsbmb.2025.106934","DOIUrl":"10.1016/j.jsbmb.2025.106934","url":null,"abstract":"<div><div>Antiestrogen therapies, such as Tamoxifen (TAM), are widely used in managing estrogen receptor-positive (ER+) breast cancer (BC); however, resistance to these agents remains a significant clinical challenge. Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, lacking approved targeted therapies and exhibiting poor patient outcomes. Transforming growth factor-β (TGF-β), a dual-functional cytokine involved in tumor suppression and progression, has gained attention for its crucial role in breast cancer development and metastasis. Therefore, evaluating the impact of antiestrogens on TGF-β pathway components may help identify novel therapeutic targets for TNBC.</div><div>This study investigated the expressions of TGF-β1, TGF-β2, and SMAD-3 in four human BC cell lines (MCF-7, MDA-MB-231, MDA-MB-468, and SK-BR-3) following treatment with optimal cell-line-specific doses of TAM and its active metabolite, 4-Hydroxytamoxifen (4-OH-TAM). In TNBC cells, antiestrogen treatment resulted in elevated TGF-β1 expression, accompanied by increased TGF-β2 and SMAD-3, particularly in metastatic MDA-MB-231 cells. Gene expression analysis also revealed that TGF-β1 was upregulated in short-term TAM treatment in MDA-MB-231 cells, whereas 4-OH-TAM had minimal impact. Long-term exposure led to opposite patterns with TGF-β1 decreasing in TAM of MDA-MB-231 cells but increasing in MCF-7 cells, while TGF-β1 elevates in 4-OH-TAM in MDA-MB-231 cells, suggesting cell line and duration-specific responses. Functional assays further showed differential anti-migratory effects, with TAM more effective in MDA-MB-231 and 4-OH-TAM in MCF-7 cells. These findings highlight TGF-β1 as a potential biomarker for TNBC and for predicting responses to antiestrogen therapies, warranting further mechanistic and functional validation.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106934"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dual carbonyl reductase activities of 17β-HSD12a during ovarian development in Japanese eel (Anguilla japonica)","authors":"Penghui Huo ,&nbsp;Shixi Chen ,&nbsp;Jing Huang ,&nbsp;Ying Yang ,&nbsp;Zhaoren Bai ,&nbsp;Yangjie Xie ,&nbsp;Xiaojian Lai","doi":"10.1016/j.jsbmb.2025.106929","DOIUrl":"10.1016/j.jsbmb.2025.106929","url":null,"abstract":"<div><div>17β-hydroxysteroid dehydrogenase subtype 12 (17β-HSD12) is responsible for the reactions between carbonyl and hydroxyl groups at the C17 position of sex steroids. Our previous research revealed that <em>hsd17b12a</em> was expressed at a high level during follicular maturation in <em>Anguilla japonica</em>, peaking at the migrating nucleus stage. This indicated the potential of 17β-HSD12 may convert 17α-hydroxyprogesterone (17OHP) into 17α,20β-dihydroxy-4-pregnen-3-one (DHP), a maturation-inducing steroid. To elucidate the functions of <em>hsd17b12a</em> in <em>A. japonica</em>, the spatiotemporal expression patterns of <em>hsd17b12a</em> were investigated, as well as its role in sex steroid hormone synthesis, and its regulation by upstream gonadotropins. The results showed that <em>hsd17b12a</em> expression was the highest in the ovaries compared to other tissues. Within the ovary, <em>hsd17b12a</em> expression peaked at the migrating nucleus stage, followed by the mid-vitellogenic stage, both significantly higher than other stages. HEK293T cells transfected with a plasmid expressing <em>A. japonica hsd17b12a</em> converted estrone, androstenedione, and 17OHP into 17β-estradiol, testosterone, and DHP, with the conversion rates of 23.70 ± 10.65, 14.95 ± 4.42, and 22.35 ± 0.53 %, respectively. <em>In vitro</em> experiment showed that stimulation with 10 ng/mL 17OHP and 100 µg/mL carp pituitary extract greatly significantly increased <em>hsd17b12a</em> expression of follicles with migrating nucleus stage, although DHP synthesis did not change significantly. The present study demonstrates that the enzyme encoded by eel <em>hsd17b12a</em> possesses both C17 and C20 carbonyl reductase activities. These findings provide new insights into the reproductive endocrine regulatory mechanisms and offer theoretical support for optimizing artificial maturation and spawning in eels.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106929"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D levels in SARS-CoV-2: Do current adequacy thresholds reflect clinical risk? Insights from a large Turkish cohort","authors":"Taner Dandinoğlu ,&nbsp;Sinem Akselim","doi":"10.1016/j.jsbmb.2025.106925","DOIUrl":"10.1016/j.jsbmb.2025.106925","url":null,"abstract":"<div><div>The clinical relevance of serum 25-hydroxyvitamin D [25(OH)D] concentrations in SARS-CoV-2 infection remains uncertain. Most thresholds used to define adequacy were developed for skeletal outcomes, and it is unclear whether they reflect immunerelated risk. To examine whether serum 25(OH)D levels are associated with disease severity, inflammatory and biochemical markers, or clinical outcomes, we conducted a retrospective cohort analysis including 1136 hospitalized patients with PCR-confirmed SARS-CoV-2 infection. Clinical severity at admission, oxygen requirement, intensive care unit transfer, invasive ventilation, inflammatory markers, length of hospital stay, and in-hospital mortality were compared across vitamin D groups. No significant associations were observed between serum 25(OH)D levels and clinical or laboratory findings. Correlation analyses likewise did not reveal meaningful relationships with inflammatory parameters. In this large hospitalized cohort with predominantly low serum 25(OH)D concentrations, we found no evidence that vitamin D status influenced COVID-19 severity or outcomes. These results indicate that commonly applied adequacy thresholds, including lower immune-related levels, may not provide useful risk stratification in hospitalized patients with COVID-19.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106925"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of bile acids in the pathogenesis and metabolic abnormalities of polycystic ovary syndrome (PCOS)","authors":"Yan Wang ,&nbsp;Xiaoli Shao ,&nbsp;Xiaoqing Yang","doi":"10.1016/j.jsbmb.2025.106919","DOIUrl":"10.1016/j.jsbmb.2025.106919","url":null,"abstract":"<div><div>Bile acid, an important molecule regulating the endocrine system and metabolism, affects glucose, lipid, and energy homeostasis in the body and has emerged as a therapeutic target for diabetes and metabolic syndrome. Polycystic ovary syndrome (PCOS) is a reproductive endocrine–metabolic disorder that is accompanied by not only obesity and insulin resistance but also bile acid metabolism disorders. In this review, we summarize the role of bile acid metabolism in three typical phenotypes of PCOS, including abnormal glucose and lipid metabolism, abnormal follicular development, and hyperandrogenism, and explore the underlying pathophysiological mechanisms. The findings provide a novel perspective for further research on PCOS and potential targets for its diagnosis and treatment.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106919"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal transcriptomic changes during neurodevelopment in a mouse model of Smith-Lemli-Opitz syndrome","authors":"Amy Li ,&nbsp;Hideaki Tomita ,&nbsp;Libin Xu","doi":"10.1016/j.jsbmb.2026.106935","DOIUrl":"10.1016/j.jsbmb.2026.106935","url":null,"abstract":"<div><div>Smith-Lemli-Opitz syndrome (SLOS) is a cholesterol biosynthesis disorder caused by mutations in the <em>DHCR7</em> gene, leading to reduced cholesterol production and accumulation of its precursor, 7-dehydrocholesterol. SLOS displays a wide range of neurodevelopmental defects, intellectual disability, and behavioral problems. However, an in-depth study of the temporal changes in gene expression in developing brains has not been conducted before. In this work, we carried out the transcriptomic analysis of whole brains from WT and <em>Dhcr7</em>-KO mice at embryonic day 12.5 (E12.5), E14.5, E16.5, and postnatal day 0 (PND0). First, we observed the expected downregulation of the <em>Dhcr7</em> gene in the <em>Dhcr7</em>-KO brains, as well as changes in other genes involved in cholesterol biosynthesis at all time points. Pathway and GO term enrichment analyses revealed affected signaling pathways and biological processes that were shared amongst time points and unique to individual time points. Specifically, pathways important for embryonic and neural development, including Hippo, Wnt, and TGF-β signaling pathways, are most significantly affected at the earliest time point, E12.5. Additionally, neurogenesis-related GO terms were enriched at earlier time points, consistent with the timing of development. Conversely, pathways related to synaptogenesis, which occur later in development than neurogenesis, are significantly affected at the later time points, E16.5 and PND0, including cholinergic, glutamatergic, and GABAergic synapses. <em>In vitro</em> neurogenesis experiments using GABAergic neuronal precursors isolated from embryonic mouse brain confirmed that loss of <em>Dhcr7</em> led to decreased proliferation and premature neurogenesis, consistent with the transcriptomic changes.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106935"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145936091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitexin reduced the dihydrotestosterone (DHT)-induced fibrosis in KGN cells by regulating the NR4A1/NLRP3 pathway","authors":"Jie-Jing Xu ,&nbsp;Chuan-Zhi Yan ,&nbsp;Zhi-Qiang Liu ,&nbsp;Hao-Ran Sun ,&nbsp;Ming-Yu Zhang ,&nbsp;Qiu-Ping Huang ,&nbsp;Chen-Xi Tong ,&nbsp;Cheng-Xue Pan ,&nbsp;Jia-Le Song ,&nbsp;Yan-Yuan Zhou","doi":"10.1016/j.jsbmb.2025.106927","DOIUrl":"10.1016/j.jsbmb.2025.106927","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in women of reproductive age, markedly impairing their health and reducing overall quality of life. Vitexin is a natural flavonoid compound that has demonstrated diverse pharmacological properties, including anti-inflammatory and antioxidant effects. The aim of this study was to investigate the effects of vitexin on dihydrotestosterone (DHT)-induced fibrosis in KGN cells, as well as its regulatory role in the NR4A1/NLRP3 signaling pathway. Experimental findings suggested that DHT treatment resulted in decreased cell viability, disrupted sex hormone balance, increased oxidative stress, and elevated levels of inflammation and fibrosis in KGN cells. However, vitexin intervention significantly reversed these pathological changes. Transcriptomics sequencing analysis and molecular docking further indicated that NR4A1 is a pivotal target of vitexin in modulating the inflammatory response. Vitexin significantly inhibited NLRP3 inflammasome-mediated inflammation by activating NR4A1, conversely NR4A1 knockdown partially attenuated the protective effects of vitexin (<em>P</em> &lt; 0.01). Therefore, vitexin was found to effectively ameliorate DHT-induced alterations in cell viability, sex hormone levels, oxidative stress, inflammation and fibrosis in KGN cells. These protective effects appear to be closely related to the regulation of the NR4A1/NLRP3 signaling pathway.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"257 ","pages":"Article 106927"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}