Journal of Steroid Biochemistry and Molecular Biology最新文献

{"title":"Interleukin-2 receptor γ blocks the development of Leydig cells from stem/progenitor cells in male rats via JAK1-STAT3 pathway and GSDMD-mediated pyroptosis","authors":"Jingyi Zheng ,&nbsp;Qingyuan Wang ,&nbsp;Huiqian Zhang ,&nbsp;Yubin Xu ,&nbsp;Feilu Wang ,&nbsp;Yiyan Wang ,&nbsp;Xiaoheng Li ,&nbsp;Ren-Shan Ge","doi":"10.1016/j.jsbmb.2026.106953","DOIUrl":"10.1016/j.jsbmb.2026.106953","url":null,"abstract":"<div><div>Interleukin-2 (IL-2) receptor γ (IL2RG) is present in the Leydig cell lineage, but its functional role remains elusive. To investigate how IL2RG impacts Leydig cell development from stem cells and elucidate the underlying mechanisms, we used a rat model of ethane dimethanesulfonate (EDS)-induced cell depletion in Wild-type (WT) and <em>Il2rg</em> knockout (KO) mice. WT and KO male rats received intratesticular IL-2 injections (1 and 10 ng/testis) from day 7 to day 21 post-EDS. Stem Leydig cells around tubules and isolated progenitor Leydig cells were cultured with IL-2 (1 and 10 ng/mL) with/without STAT3 inhibitor. Hormone levels, cell counts, gene/protein expression, and signaling pathways were analyzed. The results revealed that IL-2 significantly reduced serum testosterone levels in WT rats but had no effects in KO rats, without altering luteinizing hormone and follicle-stimulating hormone levels. Furthermore, IL-2 lowered Leydig cell numbers and the labeling index of PCNA in CYP11A1⁺ Leydig cells at 10 ng/testis, and downregulated the expression of SCARB1, HSD3B1, CYP17A1, SRD5A1, and NR5A1, as well as their corresponding mRNA levels in WT rats with no effect observed in KO rats. IL-2 also inhibited the incorporation of 5-ethynyl-2′-deoxyuridine (EdU) into stem Leydig cells in WT rats and [³H] thymidine incorporation into progenitor Leydig cells, as well as their differentiation. Importantly, the effects of IL-2 were reversed by the STAT3 inhibitor. Signaling pathway analysis showed that IL-2 exerted effects via increasing JAK1, STAT5, and STAT3 phosphorylation. This study provides insights into the inhibitory effects of IL2RG on Leydig cell development and highlights the involvement of the JAK-STAT pathway, offering potential targets for further exploration in the context of Leydig cell biology and male reproductive health.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"259 ","pages":"Article 106953"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146151290","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":"Integrative metabolomics and network pharmacology reveal the therapeutic mechanisms of Inonotus hispidus (Bull.) P. Karst. extract against primary dysmenorrhea","authors":"Qingchun Wang ,&nbsp;Haiying Bao ,&nbsp;Jingjing Zhao ,&nbsp;Hailong Liang","doi":"10.1016/j.jsbmb.2026.106957","DOIUrl":"10.1016/j.jsbmb.2026.106957","url":null,"abstract":"<div><div>Primary dysmenorrhea (PD) is a common gynecological disorder characterized by uterine hypercontraction and inflammation. This study employed an integrated strategy combining serum metabolomics, network pharmacology, and experimental validation to investigate the therapeutic potential of different extracts of <em>Inonotus hispidus</em>. In a rat PD model induced by estradiol benzoate and oxytocin, petroleum ether extracts of <em>I. hispidus</em> (MP) significantly alleviated writhing responses, attenuated uterine tissue injury, and corrected key biochemical imbalances, including the pivotal PGF₂α/PGE₂ ratio and levels of inflammatory cytokines (TNF-α, IL-6, IL-1β). Serum metabolomics analysis revealed that the therapeutic effect of MP was fundamentally linked to the systemic rectification of dysregulated arachidonic acid (AA) metabolism. Network pharmacology and subsequent experimental validation identified that MP concurrently modulates several interconnected signaling pathways. Crucially, MP activated PPARγ by promoting its dephosphorylation, which in turn potently suppressed the NLRP3 inflammasome. Concurrently, it regulated the PI3K/Akt/NF-κB survival-inflammatory axis and inhibited the RhoA/ROCK-mediated contractile pathway, reducing phosphorylation of downstream effectors MYPT1 and MLC. In vitro, the medicated serum (MP-S), containing systemically absorbed bioactive compounds, demonstrated superior and more comprehensive cytoprotection against oxytocin-induced oxidative stress, mitochondrial dysfunction, and apoptosis in rat uterine smooth muscle cells (RUSMCs) than the single compound ergosterone, underscoring the principle of multi-component synergy. Collectively, this work delineates a multi-target mechanism for MP against PD, involving the correction of AA metabolic dysregulation, activation of the PPARγ-NLRP3 axis to suppress inflammation, and inhibition of pathways driving smooth muscle hypercontraction, providing a solid scientific foundation for its development as a modern, multi-targeted therapeutic agent.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"259 ","pages":"Article 106957"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182873","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":"E3 ubiquitin ligase PELI1 promotes ferroptosis in granulosa cells in PCOS by degrading Fth1","authors":"Xiaomeng Zha ,&nbsp;Liang Chen ,&nbsp;Zhaoping Tan ,&nbsp;Tiancheng Wu ,&nbsp;Qiaohua Xiong ,&nbsp;Haihua Wang ,&nbsp;Yuanyuan Kuang ,&nbsp;Fei Xing ,&nbsp;Aihua Lu ,&nbsp;Lili Sun ,&nbsp;Yuanzhen Zhang","doi":"10.1016/j.jsbmb.2026.106948","DOIUrl":"10.1016/j.jsbmb.2026.106948","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women of reproductive age, characterized by hyperandrogenemia and obstruction of ovulation. However, the underlying mechanisms of ovarian abnormalities in PCOS remain to be investigated. In this study, we first identified altered levels of ovarian ferroptosis in the PCOS population by screening a web-based database. Further, we established a prasterone-exposed PCOS mouse model and a granulosa cell model to confirm that hyperandrogenism can lead to the development of ferroptosis in ovarian granulosa cells. The transcriptome sequencing and cellular experiments were conducted to explore the possible mechanisms. It was found that the ubiquitination pathway and P53 pathway are significantly enriched in the prasterone-exposed granulosa cells. The E3 ubiquitin ligase PELI1 gene is significantly highly expressed in PCOS ovaries and may contribute to ferroptosis by degrading FTH1. In addition, high expression of the P53 gene was associated with alterations in PELI1/FTH1. This study confirmed that hyperandrogenism can mediate the development of ovarian ferroptosis via the P53/PELI1/FTH1 pathway and the E3 ubiquitin ligase PELI1 plays an important regulatory role. In vivo, the iron death inhibitor deferoxamine mesylate could alleviate ferroptosis and follicular development disorder in the ovaries of PCOS mice. This study provides new insights into the pathological changes of PCOS ovaries and possible interventions for the treatment of PCOS.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"259 ","pages":"Article 106948"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097526","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":"Exploring the feature prioritization and data sampling of PCOS diagnosis via densely connected attention based squeeze deep learning detection model","authors":"Siji Jose Pulluparambil ,&nbsp;Subrahmanya Bhat","doi":"10.1016/j.jsbmb.2025.106933","DOIUrl":"10.1016/j.jsbmb.2025.106933","url":null,"abstract":"<div><div>Accurate and timely diagnosis remains a challenge due to the complexity of Polycystic Ovary Syndrome (PCOS) symptoms and data imbalance issues in the existing datasets. This research aims to develop a robust PCOS detection model that addresses these challenges by introducing a novel hybrid methodology with effective feature prioritization while handling data balancing issues. The research involves three major phases: pre-processing, feature selection, and PCOS detection. In the pre-processing stage, dataset balancing is emphasized by the combination of Synthetic Minority Oversampling Techniques (SMOTE) and Edited Nearest Neighbor (ENN). Under this stage, replacing null values, balancing the dataset, and dropping unnecessary columns are accomplished to increase PCOS detection accuracy. The second stage is feature selection, where a distinct hybrid bionic strategy named the Gorilla Salp Swarm Troop Model (GS2TM) is proposed to pick the optimal set of dominant features. The GS2TM algorithm reduces the feature set by 51.1 %, retaining only 23 features while achieving a state-of-the-art accuracy of 98.7 %. In addition, the Densely Connected Attention-Based Squeeze Convolutional Detection Model (DASCD) is proposed for the prediction of PCOS, in which multiple layers are adjusted in a feed-forward manner. The novelty of this work lies in the unified pipeline that simultaneously addresses three major challenges in PCOS detection, such as dataset imbalance (SMOTE-ENN), feature redundancy (GS2TM), and overfitting (DASCD with attention), providing both high accuracy and enhanced interpretability. As a result, the proposed detection model greatly improves accuracy compared to other existing ML-based strategies. Specifically, by utilizing 23 characteristics with GS2TM, the proposed model outperforms with an accuracy of 98.7 % in categorizing PCOS and non-PCOS.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"258 ","pages":"Article 106933"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893463","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":"Androgen production in adrenocortical H295R cells is regulated by thyroid hormone T3 without reciprocal thyroid axis modulation in pediatric CAH","authors":"Philipp Augsburger ,&nbsp;Therina du Toit ,&nbsp;Emre Murat Altinkiliç ,&nbsp;Sabine Hannema ,&nbsp;Christiaan de Bruin ,&nbsp;Evangelia Charmandari ,&nbsp;Erica L.T. van den Akker ,&nbsp;Christa E. Flück","doi":"10.1016/j.jsbmb.2026.106939","DOIUrl":"10.1016/j.jsbmb.2026.106939","url":null,"abstract":"<div><div>Thyroid hormones (THs) are critical regulators of human development, cellular differentiation, and metabolism. While their systemic effects are well established, their role in adrenal androgen production remains poorly defined. Moreover, potential feedback regulation of the hypothalamic–pituitary–thyroid (HPT) axis by adrenal androgens has not been thoroughly investigated. This study aimed to clarify the regulatory effects of THs on adrenal androgens and to investigate potential feedback mechanisms in patients with congenital adrenal hyperplasia (CAH). In an in-vitro experiment, treatment with 3,3′,5-triiodo-<span>L</span>-thyronine (T3) on adrenocortical carcinoma H295R cells significantly reduced dehydroepiandrosterone (DHEA) and DHEA-sulfate production while modestly increasing testosterone (T) and androstenedione (A4). These changes were associated with an increase in expression of <em>HSD3B2</em> and <em>AKR1C3</em>, and a decrease of <em>CYP17A1</em>. Transcriptomic analysis additionally revealed enrichment of pathways related to steroidogenesis and adrenal development through T3 treatment. In the clinical part of the study, hormone levels in pediatric CAH patients were analyzed. Serum free thyroxine (fT4) and thyroid-stimulating hormone (TSH) showed weak negative correlations with the adrenal androgens DHEA and A4. However, no differences in fT4 or TSH concentrations were observed between well-controlled and hyperandrogenic patients, suggesting a lack of feedback regulation by adrenal androgens on the HPT axis. In conclusion, these findings suggest that THs regulate adrenal androgen production by modulating the activity of key steroidogenic enzymes. This relationship appears to be predominantly unidirectional, with THs influencing adrenal steroidogenesis but adrenal androgens not altering HPT axis function.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"258 ","pages":"Article 106939"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981245","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":"Targeting cholinesterases with steroid hormone derivatives: Insights from In Vitro assays and molecular modeling","authors":"Jovana J. Ajduković ,&nbsp;Ana Matošević ,&nbsp;Anita Bosak ,&nbsp;Strahinja Kovačević ,&nbsp;Milica Karadžić Banjac ,&nbsp;Ivana Z. Kuzminac ,&nbsp;Andrea R. Nikolić ,&nbsp;Marina P. Savić","doi":"10.1016/j.jsbmb.2026.106950","DOIUrl":"10.1016/j.jsbmb.2026.106950","url":null,"abstract":"<div><div>Steroids represent a large family of organic compounds that, as signaling molecules, play important role in variety of physiological processes as control of metabolic pathways, inflammation processes, immune response, and growth, development and reproduction. Modifying the steroid core has allowed the creation of novel synthetic derivatives, which can offer significant benefits in medicine for treating a wide range of pathological conditions. Quite a number of natural steroids have been identified as effective inhibitors of cholinesterases, pointing them out as potential therapeutic alternatives in the application in Alzheimer’s disease (AD). Nevertheless, only a limited number of synthetic steroids have so far been studied as cholinesterase inhibitors, highlighting an opportunity for the development of new therapeutic agents derived from natural steroidal frameworks. In this study, we selected a set of structurally diverse steroid hormone derivatives and evaluated <em>in vitro</em> their inhibitory activity against human AChE and BChE. IC₅₀ values were estimated for several of the most active compounds, with pyridine-containing hydroxy derivative <strong>8</strong> exhibiting affinity toward BChE (IC₅₀ 2.76 µM), similar to that for clinically used cholinesterase inhibitors. <em>In silico</em> analyses suggest that hydrophobic interactions with key amino-acid residues predominantly govern the binding of these compounds within the enzyme’s active site.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"258 ","pages":"Article 106950"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146108279","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":"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}