Journal of Steroid Biochemistry and Molecular Biology最新文献

{"title":"Identification of cholesterol homeostasis related genes and potential pathogenesis mechanisms in ulcerative colitis","authors":"Jie Wan ,&nbsp;Yuchao Zhang ,&nbsp;Ning Ge ,&nbsp;Hongya Guan ,&nbsp;Jia Liu","doi":"10.1016/j.jsbmb.2025.106833","DOIUrl":"10.1016/j.jsbmb.2025.106833","url":null,"abstract":"<div><h3>Background and aims</h3><div>Cholesterol metabolism (CM) plays essential roles in human disease. Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with significant morbidity and healthcare burden. However, the role of CM in UC remains unclear.</div></div><div><h3>Methods</h3><div>Gene expression data of UC patients and control samples were retrieved and merged from GSE75214, GSE92415, GSE16879, and GSE48958. Differential analysis was performed for the identification of cholesterol homeostasis-related differentially expressed genes (DEGs), followed by machine learning for cholesterol homeostasis-related hub DEGs. Five cholesterol homeostasis related genes were identified. We further assessed the related pathways of 5 hub genes.</div></div><div><h3>Results</h3><div>Five overlapped cholesterol homeostasis related genes were identified by DEGs analysis. LIPC, LIPG, CETP, ABCB11, and APOH were identified as hub genes.</div></div><div><h3>Conclusions</h3><div>The current study identified 5 cholesterol homeostasis related genes, LIPC, LIPG, CETP, ABCB11, and APOH, that might play key roles in the development of UC. These findings offer new insights for further exploring UC and its underlying mechanisms.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106833"},"PeriodicalIF":2.7,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597312","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":"An in-silico investigation of protein–ligand interactions involving dietary flavonoids targeting the nucleotide-binding domain 1 (NBD1) of multidrug resistance-associated protein 1 (MRP1) to overcome multidrug resistance in cancer","authors":"Khurshid Ahmad Padder","doi":"10.1016/j.jsbmb.2025.106832","DOIUrl":"10.1016/j.jsbmb.2025.106832","url":null,"abstract":"<div><div>Multidrug resistance (MDR) continues to pose a tough challenge in the successful chemotherapeutic management of various malignancies. A key contributor to MDR is the multidrug resistance-associated protein 1 (MRP1), a member of the ATP-binding cassette (ABC) transporter family comprising 1531 amino acids. MRP1 actively extrudes a broad spectrum of chemotherapeutic agents from cancer cells, thereby reducing their intracellular accumulation and attenuating their cytotoxic effects. In this study, we performed molecular docking analyses to investigate the binding interactions between a series of naturally occurring dietary flavonoids and the Nucleotide Binding Domain 1 (NBD1) of MRP1, aiming to identify structural determinants that enhance ligand affinity and inform the selection of effective MDR modulators. All docking simulations were conducted using the Glide v5.7 software suite (Schrödinger LLC., Portland, USA) in extra precision mode (GlideXP). The 14 naturally occuring flavonoids assessed, rutin, taxifolin, myricetin, isorhamnetin, apigenin, eriodictyol, chrysin, daidzein and genistein exhibited variable binding affinities toward MRP1-NBD1, with several compounds forming key hydrogen bonds with active site amino acid residues. Notably, rutin demonstrated the highest binding affinity (docking score: –10.1958), forming highly stable hydrogen bonds with SER686 and SER689. Taxifolin and myricetin also showed favorable interactions, primarily involving SER686. These findings highlight the potential of specific dietary flavonoids to serve as functional inhibitors of MRP1-mediated drug efflux. Overall, the structural insights gained underscore the utility of flavonoid based scaffolds as promising candidates for overcoming MDR, thereby improving the therapeutic efficacy of anticancer agents.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106832"},"PeriodicalIF":2.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596048","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":"Nano-curcumin attenuates tamoxifen resistance and malignant progression in ER-positive breast cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway","authors":"Chenguang Zhang,&nbsp;Hu Wang,&nbsp;Hao Lei,&nbsp;Jianghua Ou","doi":"10.1016/j.jsbmb.2025.106825","DOIUrl":"10.1016/j.jsbmb.2025.106825","url":null,"abstract":"<div><div>Breast cancer (BC) is one of the most prevalent malignant tumors among women, with estrogen receptor (ER)-positive patients constituting approximately 70 % of all cases. Endocrine therapy is currently a treatment option for patients with ER-positive BC; however, the development of resistance significantly limits the effectiveness of this treatment. Nano-curcumin (Nano-CUR) possesses anticancer properties and enhances bioavailability by improving the hydrophobic character of curcumin (CUR). However, the underlying mechanism by which Nano-CUR affects tamoxifen (TAM) resistance in ER-positive BC remains unknown. Here, we found that Nano-CUR promoted apoptosis and cell cycle arrest, inhibited cell proliferation and reduced the levels of cancer stem cells (CSCs)-related markers, including octamer-binding protein (OCT4), Nanog homeobox (NANOG) and sex-determining region Y-box 2 (SOX2) in TAM-resistant BC cells. Additionally, Nano-CUR demonstrated the ability to inhibit tumor malignant progression in TAM-treated BC mice. Mechanistically, Nano-CUR blocked the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in MCF-7/TAM and T47D/TAM cells. The activation of this pathway by its activators (PI3K activator 740Y-P, AKT activator SC-79, and mTOR activator MHY1485) effectively alleviated the anti-tumor effect induced by Nano-CUR in TAM-resistant BC cells. Collectively, these findings reveal that Nano-CUR contributes to the reduction of tumorigenesis and TAM resistance in ER-positive BC cells by inhibiting the PI3K/AKT/mTOR signaling pathway.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106825"},"PeriodicalIF":2.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568068","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":"Gastric mucosal differentially expressed genes after bariatric surgery: Effects on sterol-related pathways","authors":"Maryam Mahjoubin-Tehran ,&nbsp;Ali H. Eid ,&nbsp;Tannaz Jamialahmadi ,&nbsp;Saheem Ahmad ,&nbsp;Safia Obaidur Rab ,&nbsp;Prashant Kesharwani ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.jsbmb.2025.106824","DOIUrl":"10.1016/j.jsbmb.2025.106824","url":null,"abstract":"<div><div>Obesity is currently recognized as a serious global health problem, which accounts for a considerable morbidity and mortality burden. Bariatric surgery is widely accepted as one of the most effective treatments for severe obesity. Roux-en-Y Gastric Bypass (RYGB) is a common type of bariatric surgery. Although the clinical impact of RYGB has been widely studied, the effects of this intervention at the molecular and genetic levels remain largely unknown. In this study, we aimed to identify differentially expressed genes in gastric mucosa after bariatric surgery <em>vs.</em> before in order to recognize genes and pathways influenced by surgery. Data of GSE76762 was downloaded from GEO (NCBI) database. Gene expression of after surgery samples were compared with before. Genes with a │Log fold change (LFC) │ &gt; 1 and adjusted p-value &lt; 0.05 were defined as differentially expressed genes. It was found that 11 genes were differentially upregulated and 6 genes were differentially downregulated after bariatric surgery. Protein-protein interactions assessed using STRNG online database was significant (p-value: 0.000202). SCD, INSIG1, CYP51A1, and LDLR have strong protein-protein interactions. Gene-gene interaction was investigated using GeneMANIA which showed the high co-expression score (97.78 %). GO and pathway enrichment analysis was investigated using EnrichR. Cholesterol Homeostasis, Sterol Homeostasis, and Cellular Response to Sterol are the best results of biological process. Metabolism of steroids, Steroid regulatory element binding proteins signaling, and Bile secretion are the best results of Reactome, WikiPathway, and KEGG, respectively. Importantly, associations of LDLR, KCNJ13, and PMP22 with Familial hypercholesterolemia, Hyperlipoproteinemia, Charcot-marie-tooth disease type 1 and 4, and Leber congenital amaurosis were discovered.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106824"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561938","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 role of cholesterol biosynthesis and metabolism causing medical complexity in patients with Smith-Lemli-Opitz Syndrome (SLOS)","authors":"Ellen Roy Elias","doi":"10.1016/j.jsbmb.2025.106822","DOIUrl":"10.1016/j.jsbmb.2025.106822","url":null,"abstract":"<div><div>Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive genetic disorder associated with complex anatomic abnormalities, accompanied by medical, developmental and behavioral challenges. It was the first human disorder identified to be caused by an error in the complex cholesterol biosynthetic pathway, more than thirty years ago. This review will cover the clinical and developmental phenotype of patients with SLOS, and the understanding of how cholesterol deficiency, accumulation of the cholesterol precursors 7- and 8-dehydrocholesterol (7-DHC and 8-DHC), and the oxidation of these precursors into toxic oxysterols, are now known to cause this complex phenotype. There is a wide range of severity in patients with SLOS. The most severely affected babies may be miscarried or die in the newborn period due to lethal congenital anomalies. The most mildly impacted patients may show few anatomic abnormalities other than 2–3 toe syndactyly, but still display cognitive and behavioral challenges along the autism spectrum. The review will also cover the medical evaluation and interventions which are recommended in caring for patients with SLOS. There is no cure for this devastating disease, but certain interventions can lead to an improved quality of life, and stabilization of progressive problems for these complex patients.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106822"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561937","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":"Suppression of human and rat 17β-hydroxysteroid dehydrogenase 1 by salicylate preservatives: 3D quantitative structure-activity relationship and in silico docking analysis","authors":"Huiqian Zhang ,&nbsp;Jiayi He ,&nbsp;Xiuwei Shen ,&nbsp;Congcong Wen ,&nbsp;Yubin Xu ,&nbsp;Feilu Wang ,&nbsp;Shaowei Wang ,&nbsp;Ren-shan Ge ,&nbsp;Xiaoheng Li","doi":"10.1016/j.jsbmb.2025.106823","DOIUrl":"10.1016/j.jsbmb.2025.106823","url":null,"abstract":"<div><div>The placenta contains 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1), an enzyme critical for converting estrone to estradiol. Salicylates, widely used as preservatives, may inhibit 17β-HSD1, but their inhibitory strength and structure-activity relationships (SAR) remain unclear. This study evaluated 13 structurally diverse salicylates, identifying potent inhibitors of human and rat 17β-HSD1. Menthyl salicylate showed the strongest inhibition in humans (IC₅₀: 5.23 μM) and rats (IC₅₀: 14.85 μM). Inhibition correlated negatively with molecular weight, volume, carbon chain length, and LogP. Mechanistic studies revealed mixed/noncompetitive inhibition in both species. 3D-QSAR and molecular docking highlighted hydrophobic, van der Waals, and hydrogen-bonding interactions at the enzyme’s active site. Key structural features, including carbon chain length and substituent patterns, determined inhibitory potency. These findings clarify SAR and suggest salicylates' potential as endocrine disruptors.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106823"},"PeriodicalIF":2.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535774","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":"Mogroside-rich extract alleviates the inflammation state in polycystic ovary syndrome rats through modulating intestinal microbiota-metabolic axis and suppressing the NF-κB/NLRP3 pathway","authors":"Shuai Li ,&nbsp;Renhong Lu ,&nbsp;Benliang Zhou ,&nbsp;Runtian Wan ,&nbsp;Yujun Yan ,&nbsp;Junhan He ,&nbsp;Jiaxin Wu ,&nbsp;Xueping Feng ,&nbsp;Xiaogan Yang ,&nbsp;Xingwei Liang","doi":"10.1016/j.jsbmb.2025.106821","DOIUrl":"10.1016/j.jsbmb.2025.106821","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS), a complex endocrine-metabolic disorder characterized by hyperandrogenism, polycystic ovarian morphology, and ovulatory dysfunction, is often associated with insulin resistance. Mogroside-rich extract (MGE) from <em>Siraitia grosvenorii</em> possesses significant anti-inflammatory and antioxidant properties. However, its potential to restore intestinal microbial homeostasis and metabolic balance in PCOS and the underlying mechanisms remain unexplored. This study investigated MGE's protective effects and mechanisms in a letrozole-induced PCOS rat model. MGE administration significantly ameliorated estrous cycle irregularities, attenuated body weight gain, reduced cystic follicle formation in ovaries, and lowered serum testosterone and insulin levels. Integrated 16S rRNA sequencing and non-targeted metabolomics revealed that MGE enriched beneficial intestinal microbiota (<em>Akkermansia</em>, <em>Parasutterella</em>), associated with anti-inflammatory effects and metabolic improvement, while suppressing pro-inflammatory <em>Corynebacterium</em>. Notably, MGE partially reversed letrozole-induced alterations in colonic metabolites, restoring levels of anti-inflammatory metabolites like butyric acid and gamma-tocotrienol. Furthermore, MGE significantly reduced ovarian pro-inflammatory cytokines and downregulated the expression of p-NF-κB and NLRP3 proteins. Collectively, these findings demonstrate that MGE ameliorates PCOS symptoms by coordinately regulating ovarian inflammation via suppressing the NF-κB/NLRP3 pathway and restoring intestinal microbiota-metabolic axis balance, highlighting its therapeutic potential for PCOS.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106821"},"PeriodicalIF":2.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501626","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":"Cholesterol acyltransferase-1: A novel diagnostic biomarker and potential therapeutic target for cancer","authors":"Shijie Mao ,&nbsp;Weimin Zhou ,&nbsp;Aiping Cheng ,&nbsp;Hengbin Cao ,&nbsp;Yun Bei","doi":"10.1016/j.jsbmb.2025.106820","DOIUrl":"10.1016/j.jsbmb.2025.106820","url":null,"abstract":"<div><div>Aberrant lipid metabolism, particularly the dysregulation of cholesterol metabolism, is a hallmark of cancer cells, facilitating cancer progression. Targeting intracellular cholesterol homeostasis has emerged as a therapeutic strategy in cancer treatment. Esterification, a critical step for cholesterol storage, mitigates cytotoxicity induced by free cholesterol. Accumulation of cholesterol ester has been extensively revealed as a promoting factor for cancer progression. Elevated expression of acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1), the primary enzyme responsible for cholesterol esterification, promotes cancer progression by activating multiple signaling pathways. ACAT-1 has garnered attention as a potential anti-cancer target, with many inhibitors developed and applied in cancer treatment. This review summarizes the effects and potential mechanisms of cholesterol ester accumulation on cancer cell proliferation, invasion, metastasis, chemotherapy resistance and immune evasion. Additionally, the role of ACAT-1 and the application of its inhibitors in various cancers are discussed, offering novel strategies for cancer therapy and diagnosis.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106820"},"PeriodicalIF":2.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144364518","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":"Analysis of star promoter in common carp and catfish testis: Role of c-jun and its association with testicular function as a transcription factor","authors":"Swathi Tenugu,&nbsp;Balasubramanian Senthilkumaran","doi":"10.1016/j.jsbmb.2025.106817","DOIUrl":"10.1016/j.jsbmb.2025.106817","url":null,"abstract":"<div><div>Steroidogenic acute regulatory protein (Star) is a key factor that predominantly mediates the rate-limiting step of steroidogenesis which involved in the translocation of cholesterol from the outer to inner mitochondrial membrane in most of the vertebrates. To understand the transcriptional regulation of <em>star</em> (<em>star</em>1) in fish, the 5’ upstream region of the <em>star</em> was cloned from both common carp and catfish genomic libraries and <em>in silico</em> promoter motif analysis predicted putative binding sites of C-jun, AP-1, Gata2, and Oct1 in common carp while C-jun, Gata1, Gata2, and Oct1 binding sites were predicted in <em>star</em> promoter of catfish. Luciferase reporter assay through sequential deletion constructs in TM3 cells revealed significantly high promoter activity (P &lt; 0.001) having C-jun site in both common carp and catfish but not with other motifs largely. Increased activity of <em>star</em> promoter was observed upon hCG induction, <em>in vitro</em>, indicating gonadotropin dependency. Site-directed mutagenesis and chromatin immunoprecipitation assays further confirmed the binding of C-jun to the upstream promoter region of <em>star</em> in both species. Expression of <em>c-jun</em> was significantly (P &lt; 0.05) higher during the spawning phase of the testicular cycle in both species. Both <em>c-jun</em> and <em>star</em> were found to be gonadotropin inducible and androgen-dependent in both species. Further, transient gene silencing through <em>c-jun</em>-siRNA in both the species decreased expression of <em>c-jun</em>, <em>star</em>, and other AP-1 factors such as <em>c-fos</em>, <em>junB</em>, <em>sox</em> family genes, steroidogenic enzyme genes, sperm-related factor, testis-related genes, along with reduced testosterone and 11-ketotestosterone levels. The protein level of C-jun was decreased upon transient gene silencing in both species. This was the first report to show that C-jun binds to the upstream promoter motif of <em>stars</em> in both common carp and catfish and also adds valuable new insights that define the molecular mechanisms of <em>c-jun</em> regulating <em>star</em> transcription during steroidogenesis in teleost and probably testicular function.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106817"},"PeriodicalIF":2.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144364517","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":"5α-reductase type 3 is a predictive marker for chemotherapy efficacy in breast cancer in an androgen-independent manner","authors":"Kanoko Nakamura ,&nbsp;Kiyoshi Takagi ,&nbsp;Mio Yamaguchi-Tanaka ,&nbsp;Ai Sato ,&nbsp;Naoki Inoue ,&nbsp;Akiko Ebata ,&nbsp;Yasuhiro Miki ,&nbsp;Minoru Miyashita ,&nbsp;Takashi Suzuki","doi":"10.1016/j.jsbmb.2025.106818","DOIUrl":"10.1016/j.jsbmb.2025.106818","url":null,"abstract":"<div><div>Breast cancer is one of the most representative sex-steroid-dependent cancers and both estrogens and androgens are locally synthesized in breast cancer tissues by sex-steroid producing enzymes. 5<span><math><mi>α</mi></math></span>-reductase (5<span><math><mi>α</mi></math></span>-Red) is an enzyme which reduces testosterone to biologically active dihydrotestosterone (DHT), serving as a regulator of intratumoral DHT levels. To date, three 5<span><math><mi>α</mi></math></span>-Red isozymes have been identified: 5<span><math><mi>α</mi></math></span>-Red types 1–3. However, 5<span><math><mi>α</mi></math></span>-Red type 3 is not fully examined in breast cancer, and its contribution to DHT synthesis is yet to be elucidated. We therefore immunolocalized 5<span><math><mi>α</mi></math></span>-Red type 3 in breast cancer tissues and correlated its immunoreactivity with intratumoral DHT levels as well as clinicopathological parameters. In the present study, 5<span><math><mi>α</mi></math></span>-Red type 3 immunoreactivity was not correlated with intratumoral DHT level. Additionally, the immunoreactivity of 5<span><math><mi>α</mi></math></span>-Red type 3 was negatively correlated with that of 17<span><math><mi>β</mi></math></span>-hydroxysteroid dehydrogenase type 5, which converts androstenedione to testosterone. In the prognostic analysis, although 5<span><math><mi>α</mi></math></span>-Red type 3 immunoreactivity was not correlated with patients’ clinical outcomes in the entire cohort of 172 breast cancer cases, it was significantly correlated with better clinical outcomes in the patients with non-luminal A type breast cancer or in those who received chemotherapy. These findings suggest that 5<span><math><mi>α</mi></math></span>-Red type 3 does not contribute to intratumoral DHT synthesis, while served as a potent predictive marker for efficacy of chemotherapy in breast cancer independent of androgen action.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106818"},"PeriodicalIF":2.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337232","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}