Steroids最新文献

{"title":"Endoplasmic reticulum stress and steroidogenic dysfunction in Leydig cells: Molecular mechanisms of UPR-mediated testosterone regulation","authors":"Luc J. Martin","doi":"10.1016/j.steroids.2025.109735","DOIUrl":"10.1016/j.steroids.2025.109735","url":null,"abstract":"<div><div>This review aims to synthesize current evidence on how endoplasmic reticulum (ER) stress affects steroidogenic function in Leydig cells. It explores the mechanisms by which ER stress activates the unfolded protein response (UPR) and autophagy pathways, ultimately influencing testosterone production and cellular homeostasis. The central research question addresses how ER stress–induced signaling modulates the transcriptional regulation of key steroidogenic enzymes and contributes to age-related declines in androgen synthesis. A comprehensive literature review was conducted using recent findings from molecular, cellular, and animal studies focusing on ER stress signaling in Leydig cells. Studies examining the roles of UPR branches (PERK, IRE1, and ATF6), autophagy pathways, and pharmacological or natural compounds modulating ER stress were analyzed to identify the regulatory mechanisms being involved and potential therapeutic implications. Evidence indicates that unresolved ER stress impairs testosterone biosynthesis by suppressing the expression of genes related to steroidogenesis. Specifically, activations of XBP1, ATF4 and ATF6, as well as their nuclear translocations, may lead to the transcriptional repression of these genes. Conversely, pharmacological ER stress inhibitors and natural antioxidants may restore these protein levels, enhance testosterone production, and improve Leydig cell function. A thorough understanding of the UPR and autophagy in Leydig cells is critical for addressing male reproductive health. ER stress is established as a key factor in the pathophysiology of impaired steroidogenesis. Therefore, targeting these stress response pathways presents a promising strategy for developing novel therapeutic interventions for testosterone deficiency and associated reproductive disorders.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"226 ","pages":"Article 109735"},"PeriodicalIF":2.3,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145726293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of reproductive steroids on autosomal dominant polycystic kidney disease progression in women","authors":"Noor Saeed Hasan,&nbsp;Warren Thomas","doi":"10.1016/j.steroids.2025.109726","DOIUrl":"10.1016/j.steroids.2025.109726","url":null,"abstract":"<div><div>Autosomal dominant polycystic kidney disease (ADPKD) is a disease characterized by the growth of fluid filled cysts in the kidney. ADPKD arises due to a heritable mutation in the polycystic kidney disease 1 gene (PKD1) and polycystic kidney disease 2 gene (PKD2) ultimately leading to kidney failure. Incidence in males and females is equivalent, but differences arise in progression. This review brings together various studies regarding the impact of cyclic hormone changes on ADPKD progression, bringing attention to gaps in knowledge that needs to be addressed. Circulating hormones play a crucial role in the pathogenesis of the disease, particularly the renin angiotensin system. The physiological actions of estrogen tend to have a protective effect on the kidney, contributing to a slowed progression in females. The hormonal changes of the menstrual cycle and at menopause result in changes in pathology via blood pressure fluctuation, promotion of renal repair and prevention of renal scarring and damage. Signaling pathways that are involved in cyst growth such as cAMP, mTOR, MAPK/ERK, and PI3K/Akt are modulated by estrogen, providing insights into potential mechanisms. Estrogen-based hormonal therapy is being investigated for its efficacy in improving renal function post menopause.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"226 ","pages":"Article 109726"},"PeriodicalIF":2.3,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An unexpected oxidative E/F ring opening in the side chain of steroid sapogenins produced by silica gel supported Jones Reagent","authors":"Juan E. Hernández-Martínez,&nbsp;Karen M. Ruíz-Pérez,&nbsp;Jacqueline Sanchez-Flores,&nbsp;Martin A. Iglesias-Arteaga","doi":"10.1016/j.steroids.2025.109725","DOIUrl":"10.1016/j.steroids.2025.109725","url":null,"abstract":"<div><div>In contrast with previous results in which the spiroketal side chain of steroid sapogenin has proven to be unreactive to Jones Reagent, treatment these sapogenins with silica gel-supported Jones Reagent triggered the oxidative opening of the spirostanic side chain producing moderate to good yields of sapogenoic acids that bear carbonyl functions at C-16 and C-22 and a C-26 carboxylic group. Based on these findings, a procedure that allows the synthesis of sapogenoic acids minimizing contamination by chromium salts was designed.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"226 ","pages":"Article 109725"},"PeriodicalIF":2.3,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145640036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LC-MS/MS quantitation of the primary reduced metabolites of progesterone in serum during the third trimester of human pregnancy reveals a potential role for 20β-hydroxyprogesterone and 5β-dihydroprogesterone in functional progesterone withdrawal","authors":"Edward Hinchliffe ,&nbsp;Alexander Heazell","doi":"10.1016/j.steroids.2025.109724","DOIUrl":"10.1016/j.steroids.2025.109724","url":null,"abstract":"<div><div>Progesterone (P4) is an essential steroid hormone synthesised by the placenta required for the maintenance of pregnancy. In humans, the metabolism of P4 has been implicated in functional P4 withdrawal prior to parturition. We have developed a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantitation in human serum of pregnenolone, P4 and its four primary reduced metabolites; 20α-hydroxyprogesterone (20α-OHP), 20β-hydroxyprogesterone (20β-OHP), 5α-dihydroprogesterone (5α-DHP) and 5β-dihydroprogesterone (5β-DHP). Following solid phase extraction, chromatographic baseline separation of each steroid was achieved using a biphenyl stationary phase within a 10.0 min runtime, followed by MS detection on a Sciex 6500+. The LC-MS/MS method was validated in accordance with published guidelines, confirming acceptable analytical performance pertaining to linearity, imprecision, accuracy, sensitivity, matrix effects, specificity and carryover. The method was applied to a large cohort of third trimester pregnancies with verified uncomplicated neonatal outcomes. Maternal circulating concentrations of P4, 20α-OHP, 20β-OHP, and 5α-DHP positively correlated with fetal gestational age. The ratio of P4:20β-OHP declined significantly throughout the third trimester, whilst the ratio of P4:5β-DHP increased at full term from 40 weeks’ gestation. These findings may indicate a substantive role for β-reduction of P4 in the mechanics of functional P4 withdrawal, either via depletion of the overall pool of bioactive P4 or competitive binding of these metabolites to the P4 receptor in maternal and fetal tissue. Additionally, detailed characterisation of the normal maternal steroidome will facilitate the study of dysregulated placental steroidogenesis, which has been implicated in the pathogenesis of the major obstetric syndromes causing poor pregnancy outcomes.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109724"},"PeriodicalIF":2.3,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semi-synthetic sapogenin derivatives inhibit inflammation-induced tumorigenic signaling alterations in prostate carcinogenesis","authors":"Bilge Debelec-Butuner ,&nbsp;Mert Burak Ozturk ,&nbsp;Ozgur Tag ,&nbsp;Ismail Hakki Akgun ,&nbsp;Erdal Bedir","doi":"10.1016/j.steroids.2025.109723","DOIUrl":"10.1016/j.steroids.2025.109723","url":null,"abstract":"<div><div>Prostatic inflammation plays a pivotal role in prostate cancer development and progression via altering key cellular mechanisms, including proliferation, metastasis, and angiogenesis. Therefore, the use of anti-inflammatory drugs could provide a valid contribution to PCa prevention and treatment. In our research, we explored semi-synthetic derivatives of cycloastragenol (<strong>CA</strong>) and astragenol (<strong>AG</strong>) to assess their potential to inhibit inflammation-mediated tumorigenic signaling.</div><div>Building on our previous findings, which demonstrated their inhibitory activity on NFκB, we discovered that these molecules also suppress inflammation-induced cell proliferation and migration through distinct mechanisms. They effectively alleviated inflammation by reducing levels of ROS, NO, and VEGF expression. Furthermore, these molecules partially restored the expression of AR and the tumor suppressor NKX3.1, both of which are critical in prostate tumorigenesis within an inflammatory microenvironment. They also reversed inflammation-induced activation of Akt and β-catenin signaling, suggesting their potential to inhibit inflammation-related prostate tumorigenesis. Our study further demonstrated that these molecules exhibited dose-dependent effects on inducing cell cycle arrest and apoptosis, as evidenced by increased p21 and decreased BCL-2 protein levels, leading to activated cell death and suppressed cellular migration.</div><div>In conclusion, these semi-synthetic sapogenol derivatives demonstrate significant potential as anti-inflammatory and anticancer agents, offering a promising approach for targeting prostatic inflammation and inflammation-driven prostate carcinogenesis.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109723"},"PeriodicalIF":2.3,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145605725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifungal ergostane-type steroids from endophytic fungus Xylaria sp. VDL4","authors":"Jiao Yao ,&nbsp;Lin-Hong Lu ,&nbsp;Sheng-Yun Wei ,&nbsp;Ting Wu ,&nbsp;Wei Yang ,&nbsp;Wei-Hua Wang ,&nbsp;Fa-Zhong Yang ,&nbsp;Yun-Xian Li ,&nbsp;Ping Zhao ,&nbsp;Guo-Lei Zhu","doi":"10.1016/j.steroids.2025.109722","DOIUrl":"10.1016/j.steroids.2025.109722","url":null,"abstract":"<div><div>Three ergostane-type steroids, including one rare C-29 methylated xylarstane A (<strong>1</strong>) and one C22,23-epoxied xylarstane B (<strong>2</strong>), along with one reported compound <strong>3</strong>, were isolated from the endophytic fungus <em>Xylaria</em> sp. VDL4 harbored within the medicinal plant <em>Vaccinium dunalianum</em>. The structures of novel compounds were elucidated through comprehensive spectroscopic analysis, DP4⁺-validated theoretical ¹³C nuclear magnetic resonance (NMR) calculations, and electronic circular dichroism (ECD) calculations. The antifungal activities of the isolates against four phytopathogens were assessed <em>in vitro.</em> Compounds <strong>1</strong> and <strong>3</strong> exerted significant inhibition against <em>Alternaria solani</em> and <em>Botrytis cinerea</em> respectively, both with minimal inhibitory concentration (MIC) of 12.5 μg/mL, comparing with the positive control (Carbendazim and Thiabendazole, MICs = 12.5–25.0 μg/mL).</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109722"},"PeriodicalIF":2.3,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro metabolic profiling of 6-chloro-testosterone and 6-ene-testosterone by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-time of flight (GC-TOF) mass spectrometry","authors":"Dayamin Martínez_Brito ,&nbsp;Carlotta Stacchini ,&nbsp;Cristiana Colamonici ,&nbsp;Davide Curcio ,&nbsp;Francesco Botrè ,&nbsp;Xavier de la Torre","doi":"10.1016/j.steroids.2025.109720","DOIUrl":"10.1016/j.steroids.2025.109720","url":null,"abstract":"<div><div>Among the phase-I reactions of 6-chloro-testosterone (6-CT), the reductive and oxidative dehalogenation, as well as the dehydrogenation, have been described here. One of the metabolic products could be the 6-ene-testosterone (6-ene-T). The goal of this work was to study the <em>in vitro</em> metabolism of 6-CT and 6-ene-T after incubation with human liver microsomes (HLM), analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-time-of-flight-mass spectrometry (GC-TOF).</div><div>6-CT showed a more extensive metabolism compared to 6-ene-T, with the formation of a larger number of metabolites. In contrast, 6-ene-T, which potentially preserves the C6<img>C7 double bond in most of its metabolites, showed fewer metabolites. Therefore, after incubation with HLM, the main metabolic routes of 6-ene-T are the oxidation of the hydroxyl group on C17β, retaining the double bond C6<img>C7 to form 6-ene-androstenedione, and the hydroxylation on C6. On the other hand 6-CT metabolism produced chlorinated and non-chlorinated metabolites as a result of the phase I reactions which included oxidation, reduction, hydroxylation and (oxidative and reductive) dehalogenation. Specifically for 6-CT, it should be considered that the introduction of a chlorine atom in the 6α position of T may lead to a shift in the metabolic pathway, favoring the formation of 5β-reduced metabolites over 5α-reduced metabolites, due to the steric and electronic effects of the chlorine atom on the interaction between the steroid molecule and the 5α-reductase enzyme.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109720"},"PeriodicalIF":2.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure-response of serum biomarkers to vamorolone, a dissociative corticosteroidal anti-inflammatory drug, in 4- to <7-year children","authors":"Swati Mummidivarpu ,&nbsp;Utkarsh J. Dang ,&nbsp;Michael Ziemba ,&nbsp;Yetrib Hathout ,&nbsp;Paula R. Clemens ,&nbsp;Jesse Damsker ,&nbsp;Laura Hagerty ,&nbsp;William J. Jusko ,&nbsp;Edward C. Smith ,&nbsp;Jean K. Mah ,&nbsp;Michela Guglieri ,&nbsp;Yoram Nevo ,&nbsp;Nancy Kuntz ,&nbsp;Craig M. McDonald ,&nbsp;Monique M. Ryan ,&nbsp;Diana Castro ,&nbsp;Richard S. Finkel ,&nbsp;Laurie S. Conklin ,&nbsp;John M. McCall ,&nbsp;Kanneboyina Nagaraju ,&nbsp;Eric P. Hoffman","doi":"10.1016/j.steroids.2025.109721","DOIUrl":"10.1016/j.steroids.2025.109721","url":null,"abstract":"<div><h3>Objectives</h3><div>Corticosteroid agonists of the glucocorticoid receptor are a mainstay of therapeutics for pro-inflammatory conditions. Vamorolone is a novel partial agonist that is differentiated from the other members of the corticosteroid class by non-metabolism by 11β-hydroxysteroid dehydrogenases, antagonism of the mineralocorticoid receptor, and differential co-factor binding. Our objective was to define the pharmacodynamic response of serum proteins to vamorolone.</div></div><div><h3>Methods</h3><div>Clinical trial participants with Duchenne muscular dystrophy (4 to &lt;7 yr; n = 39; mean [SD] age = 5.3 [1.0]) enrolled in a multiple ascending dose study of vamorolone were studied (24-fold dose range). Dose-response and exposure–response of 1,305 serum proteins were defined by intra-subject longitudinal changes (baseline vs. Day 14).</div></div><div><h3>Results</h3><div>Dose-response analysis identified 159 of 1,305 serum proteins as dose-responsive to vamorolone (12 % of proteins tested; 20 % increased, 80 % decreased). Two inflammatory networks showed drug-responsive suppression. One centered on extracellular serine proteases and lymphotoxins (PI3, KLK7, KLK8, KLK11, lymphotoxins A, B) converging on NFκB. The second centered on cytokines (CCL22/MDC, CCL21, CCL14, CXCL12) and IL23 signaling. In the IL23 network, acutely responsive anti-inflammatory proteins included increases of an inhibitor of IL17 signaling (IL17RC) and decreases of IL23 (IL12B:IL23A). A protein associated with resistance to environmental microbes, PTP1C, showed strong induction and is a novel candidate for aspects of corticosteroid efficacy. Two networks of cell-associated proteins were identified as drug responsive that may represent muscle tissue response (efficacy): connective tissue remodeling upstream of Notch signaling, and plasma membrane proteins impinging on AKT1 signaling.</div></div><div><h3>Conclusion</h3><div>The serum proteome pharmacodynamics of the response to vamorolone was defined.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109721"},"PeriodicalIF":2.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of dihydrobetulinic acid as a potent small molecule CD73 inhibitor","authors":"Hongling Wang ,&nbsp;Yanming Zhang ,&nbsp;Chunyang Lou ,&nbsp;Xuliang Chang ,&nbsp;Hang Yang ,&nbsp;Daozuan Zhang ,&nbsp;Haijun Ma ,&nbsp;Zhenyuan Miao","doi":"10.1016/j.steroids.2025.109719","DOIUrl":"10.1016/j.steroids.2025.109719","url":null,"abstract":"<div><div>Betulinic acid (BA) is a pentacyclic triterpene compound with various biological activities. Herein, we designed and synthesized a series of dihydrobetulinic acid (DHBA) and its derivatives for the discovery of potent ecto-5′-nucleotidase (CD73) inhibitors. Biological evaluation of DHBA and its derivatives led to the disclosure of three active compounds DHBA, <strong>ZM792</strong> and <strong>ZM905</strong>. Further investigation of antitumor immunity revealed that DHBA could effectively restore the function of CD4⁺ T cells. These results provide novel insights for future endeavors in developing novel agents derived from natural product targeting CD73 enzyme.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109719"},"PeriodicalIF":2.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of vitamin D on high-fat-diet-induced metabolic dysfunction-associated steatotic liver disease in mice","authors":"Amal A. Mohamed ,&nbsp;Wael Hafez ,&nbsp;Said El-Feky ,&nbsp;Mona G. Khalil ,&nbsp;Amina S. Soliman ,&nbsp;Karima Nasraldin ,&nbsp;Ingy M. Ibrahim ,&nbsp;Hanan A. Hegazy ,&nbsp;Weam Shaheen ,&nbsp;Abbas M. Abbas ,&nbsp;Hager Shaheen ,&nbsp;Marian FL. Abdelmalak ,&nbsp;Hany N. Azzam ,&nbsp;Omnia Ezzat ,&nbsp;Noheir Ashraf Ibrahem Fathy Hassan ,&nbsp;Omer Al Dulaimi ,&nbsp;Naglaa K. Madkour","doi":"10.1016/j.steroids.2025.109718","DOIUrl":"10.1016/j.steroids.2025.109718","url":null,"abstract":"<div><h3>Background</h3><div>Genetics, inflammation, and nutrition contribute to the pathogenesis of metabolic dysfunction–associated steatotic liver disease (MASLD).</div></div><div><h3>Aim</h3><div>This preclinical study evaluated the protective effect of vitamin D supplementation against high-fat-diet–induced MASLD in a mouse model and compared physiological, inflammatory, and molecular responses across high-fat and low-fat dietary regimens, with and without vitamin D co-administration.</div></div><div><h3>Methods</h3><div>Forty-five healthy male albino Swiss mice (aged 6 weeks; 30 ± 10 g) were randomly assigned to five groups (n = 9 each): control (standard diet), HFD (high-fat diet), HFD + vitamin D, LFD (low-fat diet), and LFD + vitamin D. Vitamin D (20 000 IU/kg/week) was administered via drinking water for 12 weeks. Body weight, visceral adiposity, and liver indices were recorded, while serum biochemical markers, inflammatory cytokines, and expression of Toll-like receptor 7 (TLR7) and microRNA-155 (miR-155) were analyzed at endpoint.</div></div><div><h3>Results</h3><div>HFD-fed mice exhibited marked increases in ALT (51.44 ± 9.68 U/L), AST (56.67 ± 13.29 U/L), ALP (135.01 ± 16.19 U/L), AFP (28.56 ± 5.31 ng/mL), CRP (20.87 ± 5.56 mg/L), total cholesterol (225.00 ± 27.16 mg/dL), LDL (137.56 ± 28.66 mg/dL), and triglycerides (210.56 ± 28.71 mg/dL), accompanied by reduced HDL (30.24 ± 9.86 mg/dL) compared with controls. Pro-inflammatory cytokines TNF-α (28.33 ± 2.96 pg/mL), IL-6 (121.78 ± 8.98 pg/mL), and the expression of TLR7 (2.92 ± 0.83) and miR-155 (2.75 ± 0.77) were significantly elevated relative to normal-fed mice (miR-155: 0.84 ± 0.26). Vitamin D supplementation significantly ameliorated these metabolic and inflammatory disturbances.</div></div><div><h3>Conclusions</h3><div>Vitamin D supplementation mitigated HFD-induced hepatic injury, dyslipidemia, and inflammatory activation by modulating the miR-155/TLR7 axis. These findings highlight vitamin D as a potential adjunctive strategy for preventing or attenuating MASLD progression under high-fat dietary conditions.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"225 ","pages":"Article 109718"},"PeriodicalIF":2.3,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}