Journal of Steroid Biochemistry and Molecular Biology最新文献

{"title":"1,25(OH)2D3 up-regulated mitochondrial dynamics and biogenesis to modulate steroidogenesis in the scent glands of muskrats (Ondatra zibethicus)","authors":"Qingjing Gao,&nbsp;Ke Shi,&nbsp;Xinjing Shi,&nbsp;Yuning Liu,&nbsp;Haolin Zhang,&nbsp;Qiang Weng","doi":"10.1016/j.jsbmb.2025.106787","DOIUrl":"10.1016/j.jsbmb.2025.106787","url":null,"abstract":"<div><div>Vitamin D₃ plays a crucial regulatory role in steroid hormone production, but the specific mechanism remains not fully understood. In this study, we investigated the expression and distribution patterns of Vitamin D receptor (VDR), vitamin D₃ metabolic enzymes (CYP2R1, CYP27B1 and CYP24A1), mitochondrial dynamics and biogenesis (proteins and genes), and steroidogenic enzymes in the scent glands of muskrats during the breeding and non-breeding periods. VDR, vitamin D₃ metabolic enzymes, mitochondrial dynamics and biogenesis-related proteins, and steroidogenic enzymes were immunolocalized in the scent glandular cells in both breeding and non-breeding seasons, with stronger immunostaining in the breeding season. The mRNA expression levels of <em>Cyp27b1</em>, <em>Cyp24a1</em>, <em>Vdr</em>, <em>Mfn1</em>, <em>Opa1</em>, <em>Vdac</em>, <em>Tfam</em>, <em>Pgc1b</em>, <em>Star</em>, <em>Cyp11a1</em>, <em>Cyp17a1</em>, and <em>Cyp19a1</em> were higher in the scent glands during the breeding season than those of the non-breeding season. 1,25(OH)₂D₃ concentration were positively correlated with the mean mRNA expression levels of mitochondrial dynamics and biogenesis marker genes and steroidogenic enzymes in the scent glands. The concentrations of circulating testosterone (T) and 17β-estradiol (E₂), and 1,25(OH)₂D₃ of the scent glands were also significantly higher in the breeding season. Additionally, the addition of 1,25(OH)₂D₃ to the primary scent glandular cells <em>in vitro</em> increased the expression levels of mitochondrial dynamics and biogenesis-related genes and steroidogenic enzymes in the scent glands of muskrats. These findings suggested that 1,25(OH)₂D₃ might promote the secretion of steroid hormones by upregulating the mitochondrial dynamics and biogenesis in the scent glands of muskrats.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106787"},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106529","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":"Strontium regulating lipid metabolism of bovine hepatocytes via SIRT1/SREBPs pathway","authors":"Fangyuan Zeng,&nbsp;Wenjuan Hu,&nbsp;Haichuan Xu,&nbsp;Xinxin Wang,&nbsp;Chenxu Zhao,&nbsp;Yazhou Wang,&nbsp;Jianguo Wang","doi":"10.1016/j.jsbmb.2025.106785","DOIUrl":"10.1016/j.jsbmb.2025.106785","url":null,"abstract":"<div><div>Periparturient dairy cows are susceptible to negative energy balance (NEB), which triggers excessive adipose mobilization, leading to elevated plasma non-esterified fatty acids (NEFA) and hepatic lipid accumulation. While strontium (Sr) has shown metabolic regulatory potential, its role in hepatic lipid homeostasis remains unclear. Using an NEFA-induced lipid accumulation model in bovine hepatocytes, we demonstrated that Sr (5–20 μM) significantly reduced intracellular triglyceride (TG) and total cholesterol (TC) levels. Further mechanistic studies revealed that Sr enhances SIRT1 expression and suppresses the expression and nuclear translocation of SREBP-1C/SREBP2, thereby downregulating downstream lipogenic enzymes including ACC, FASN, SCD1, and HMGCR. Molecular docking indicated that Sr²⁺ binds with high affinity to Asp-481/483 of SIRT1, while SIRT1 inhibition with EX-527 abolished Sr-mediated lipid-lowering effects. Additionally, Sr promoted PPARα nuclear translocation to enhance β-oxidation and upregulated LDLR expression to facilitate lipid efflux. This study elucidated the multi-target molecular mechanism of Sr alleviating lipid metabolism disorders in bovine hepatocytes through the SIRT1/SREBPs pathway, providing a theoretical foundation for the application of Sr in preventing metabolic diseases in dairy cows.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106785"},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124028","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":"Bisphenol Z inhibits the function of Leydig cells via upregulation of METTL3 expression in adult male rats","authors":"Yingna Zhai ,&nbsp;Huiqian Zhang ,&nbsp;Chunnan Hu ,&nbsp;Qingyuan Wang ,&nbsp;Shaowei Wang ,&nbsp;Ren-Shan Ge ,&nbsp;Xiaoheng Li","doi":"10.1016/j.jsbmb.2025.106786","DOIUrl":"10.1016/j.jsbmb.2025.106786","url":null,"abstract":"<div><div>The use of bisphenol A has been restricted due to its toxicity. However, the impact of its substitute, bisphenol Z (BPZ), on Leydig cell function remains uncertain. We aimed to examine the associations between BPZ exposure and the disruption of Leydig cell function via upregulating <em>Mettl3</em> and inducing oxidative stress. To address this, <em>in vivo</em>, male adult Sprague-Dawley rats received BPZ (0, 1, 10, or 100 mg/kg/d orally) for 7 days, and <em>in vitro</em>, purified Leydig cells were treated with BPZ (0–20 μM, 24 h). Leydig cell morphology and function were assessed. The results showed that BPZ did not alter Leydig cell quantity but notably decreased serum testosterone levels. Furthermore, it significantly downregulated the expression levels of genes and proteins (SCARB1, STAR, CYP17A1, HSD17B3, and INSL3) in Leydig cells. Concurrently, BPZ treatment led to diminished expression of antioxidant genes (<em>Gpx1</em> and <em>Cat</em>), an upregulation in m6A related gene (<em>Mettl3</em>) subsequent to the enrichment of RNA methylation fragments in the testis. <em>In vitro</em> analysis of primary Leydig cells demonstrated that BPZ heightened oxidative stress and diminished testosterone production. In conclusion, BPZ reduces rat testosterone by downregulating steroidogenic genes (<em>Star</em>, <em>Scarb1</em>, <em>Cyp17a1</em>, and <em>Hsd17b3</em>) via METTL3-m6A-<em>Camkk2</em> pathway, impairing Leydig cell function.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106786"},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099146","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":"Protective effect of preconception high dose vitamin D3 supplementation in gestational diabetes mellitus rats via modulation of placental LCPUFA metabolism, one carbon cycle components, inflammation, oxidative stress, and angiogenesis","authors":"Anindita A. Nandi,&nbsp;V.H. Patel","doi":"10.1016/j.jsbmb.2025.106775","DOIUrl":"10.1016/j.jsbmb.2025.106775","url":null,"abstract":"<div><div>Gestational diabetes mellitus (GDM), one of the most common pregnancy complications, adversely affects maternal and fetal health. This study investigated the impact of vitamin D3 (VD3) deficiency or supplementation on placental long chain polyunsaturated fatty acid (LCPUFA) metabolism, one-carbon cycle metabolites, inflammation, oxidative stress, angiogenesis, and birth outcomes in a GDM rat model. Wistar rats were divided into five groups: Control (1000 IU VD3/kg diet), Vitamin D Deficient (VDD, 0 IU VD3/kg diet), GDM (1000 IU VD3/kg diet + GDM), VD3 supplementation with 1500 IU (VDS-1500 +GDM), and VD3 supplementation with 10,000 IU (VDS-10,000 +GDM). GDM was induced using a high-fat, high-sugar diet and streptozotocin. Diets were provided from weaning through pregnancy. Only the VDS-10,000 +GDM group achieved sufficient serum 25(OH)D levels (&gt;30 ng/ml). 10,000 IU/kg VD3 supplementation reduced gestational weight gain and improved fetal/placental weight ratios. It reduced the levels of FBS, fasting insulin, and HOMA-IR, while increased HOMA-IS. It regulated calcium homeostasis by decreasing parathyroid hormone and increasing phosphorous levels. It normalized one-carbon metabolites, reducing homocysteine and increasing folate levels. Both doses of VD3 supplementation mitigated oxidative stress, reducing malondialdehyde levels, which was higher in GDM and VDD groups. It restored LCPUFA profiles, increasing arachidonic acid and decreasing n-6 linoleic acid levels. High-dose VD3 reduced elevated plasma and placental TNF-α levels and downregulated IL-6 mRNA in the GDM group, while IL-6 protein levels remained comparable. The protein and mRNA levels of both VEGF and VEGF-R1 were higher in GDM group. 10,000 IU VD3 reduces VEGF levels whereas, 1500 IU VD3 reduces VEGF-R1 levels. High-dose VD3 supplementation (10,000 IU/kg) during pregnancy effectively improved vitamin D status and positively influenced placental metabolic pathways, oxidative stress, inflammation, and angiogenesis, thereby improving pregnancy outcomes in GDM.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106775"},"PeriodicalIF":2.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051323","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":"Immobilization of cholesterol oxidases on functionalized Silica Nanoparticles for biotransformation of cholesterol and 7-ketocholesterol","authors":"Shubhrima Ghosh ,&nbsp;Razi Ahmad ,&nbsp;Vikas Kumar Gautam ,&nbsp;Sunil Kumar Khare","doi":"10.1016/j.jsbmb.2025.106774","DOIUrl":"10.1016/j.jsbmb.2025.106774","url":null,"abstract":"<div><div>Cholesterol oxidation leads to the development of several oxysterols such as 7-ketocholesterol (7KC), which are linked to various age-related conditions. An approach to reduce their toxicity is proposed using enzymes from microbial sources to degrade them. Our earlier studies identified <em>Pseudomonas aeruginosa</em> PseA and <em>Rhodococcus erythropolis</em> MTCC 3951 as potential strains capable of using 7KC as their sole carbon source. These strains produced cholesterol oxidase as the primary enzyme in the degradation pathway. To enhance applicability, cholesterol oxidase (ChOx) enzymes from <em>P. aeruginosa</em> PseA (ChOxP), <em>R. erythropolis</em> MTCC 3951 (ChOxR), and a commercial variant from <em>Streptomyces</em> sp. (ChOxS) were immobilized on silane functionalized silica nanoparticles (SNP) using covalent-coupling methods. The immobilization efficiency was 68 %, 86 %, and 83 % for ChOxP, ChOxR, and ChOxS respectively. The catalytic efficiency of the immobilized enzyme was nearly twice that of the free enzyme, with increased stability across a wide range of temperatures (10–70°C) and pH levels (4.0–9.0), although the optimum pH (7.5) and temperature (30°C) remained unchanged. The nano-immobilized cholesterol oxidases were reusable up to 10 cycles. Further, enzyme immobilization on nanoparticles was confirmed by FTIR, SEM, and TEM. Biotransformation of cholesterol and 7KC using the nanobioconjugates produced pharmaceutically important molecules 4-cholesten-3-one and 4-cholesten-3,7-dione respectively.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106774"},"PeriodicalIF":2.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024266","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":"(-)-Epigallocatechin-3-gallate and chlorogenic acid in combination with vitamin D as a therapeutic approach for letrozole-induced polycystic ovary syndrome (PCOS) rats: Biochemical and hormonal modulation","authors":"Sana Siddiqui ,&nbsp;Rizwan Ahmad ,&nbsp;Tariq Aziz ,&nbsp;Aijaz Ahmed Khan ,&nbsp;Hamid Ashraf ,&nbsp;Shagufta Moin","doi":"10.1016/j.jsbmb.2025.106772","DOIUrl":"10.1016/j.jsbmb.2025.106772","url":null,"abstract":"<div><div>Treatment with phytochemicals have shown promising results in managing various diseases including Polycystic ovary syndrome (PCOS) which is an endocrine gynecological disorder affecting reproductive aged women. This study has demonstrated that Epigallocatechin-3-gallate (EGCG) and chlorogenic acid (CGA) in combination with vitamin D can significantly reduce PCOS like characteristics including ovarian cysts, hyperandrogenism, fasting blood glucose level, insulin resistance, hyperlipidaemia, ROS formation, oxidative stress, DNA damage, and ovarian histomorphology in letrozole induced PCOS rats. PCOS was induced in female Wistar rats by giving 1 mg/kg/day letrozole for 21 days through oral gavage. EGCG (100 mg/kg/day) and CGA (120 mg/kg/day) in combination with vitamin D (25 mcg/kg/day) was given orally for 15 days, from day 21–35. Metformin treatment was used as a positive control. Histological, microscopic analysis, and chemiluminescent immunoassays were performed to evaluate decrement in PCOS like symptoms. Nitric oxide (RNS) production, antioxidant status, and the generation of reactive oxygen species (ROS) were also assessed. Ovary homogenates and plasma samples of rats were also examined for markers of protein, lipid, and DNA oxidation. Activities of enzymatic antioxidants (superoxide dismutase, catalase, glutathione reductase, Paraoxonase-1 status) were also evaluated. EGCG + vitamin D and CGA + vitamin D has been found to restore hormonal balance by modulating steroidogenic enzymes, they also improved antioxidant enzyme activity including SOD, catalase, glutathione reductase, PON-1 arylesterase, PON-1 CMPAase, etc. Similarly, EGCG + vitamin D and CGA + vitamin D treatment have shown efficacy in normalizing the estrus cycle, reducing ovarian cysts, and improving ovarian histomorphology. They also assisted in alleviating triglycerides and cholesterol levels and maintained liver function enzymes level. However, EGCG + vitamin D proves to have better therapeutic potential modulates glucose metabolic pathways, by reducing blood glucose levels, advanced glycation end product formation, decreasing ROS generation and oxidative stress; consequently, lowers hyperandrogenism and insulin resistance. Overall, EGCG + vitamin D treatment offers a comprehensive approach in managing PCOS by targeting multiple pathways associated with this disorder, making it a potential alternative to conventional therapies.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106772"},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929000","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":"FSH, LH, lipid and adipokines in Polycystic Ovary Syndrome: Clinical biochemistry insights for diagnosis and management","authors":"Wafa Mansor Merza,&nbsp;Abeer Khalid Yaseen,&nbsp;Maha Adel Mahmood","doi":"10.1016/j.jsbmb.2025.106773","DOIUrl":"10.1016/j.jsbmb.2025.106773","url":null,"abstract":"<div><div>Polycystic Ovary Syndrome (PCOS) is a common endocrine syndrome characterized by hormonal imbalances, metabolic disturbances, and clinical symptoms. The pathophysiology of this syndrome involves disruptions in hormonal signaling, particularly changes in levels of luteinizing hormone (LH), and follicle-stimulating hormone (FSH) which can lead to anovulation and infertility. Additionally, insulin resistance and dysfunctional adipose tissue are other complicating factors of this condition. Biochemical markers such as FSH, LH, lipid profiles, and adipokines (like leptin and adiponectin) are crucial for diagnosing PCOS and assessing its severity. In PCOS patients, elevated LH levels relative to FSH are typically observed, and lipid abnormalities increase the risk of cardiovascular diseases. Diagnosing this syndrome usually requires comprehensive biochemical tests to confirm hyperandrogenism and insulin resistance. Management strategies include lifestyle modifications and pharmacological interventions aimed at correcting hormonal imbalances and dyslipidemia. Monitoring treatment outcomes through biochemical markers is essential for evaluating therapeutic efficacy. This review article examines the roles of FSH and LH hormones, lipids, and adipokines in the diagnosis and management of PCOS, emphasizing the importance of clinical biochemistry in improving diagnostic and treatment methods for this disorder. Furthermore, research into identifying emerging biomarkers for early diagnosis and new therapeutic targets is suggested.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"251 ","pages":"Article 106773"},"PeriodicalIF":2.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912642","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":"Synthesis and preliminary evaluation of estradiol diselenocyanate derivatives as potential antitumor agents","authors":"Yanmin Huang,&nbsp;Yang Cheng,&nbsp;Wenhao Tian,&nbsp;Zhiping Liu,&nbsp;Chunfang Gan,&nbsp;Haifeng Chen,&nbsp;Tao Gan,&nbsp;Chunrui Cai,&nbsp;Jianguo Cui","doi":"10.1016/j.jsbmb.2025.106771","DOIUrl":"10.1016/j.jsbmb.2025.106771","url":null,"abstract":"<div><div>Cancer is a prominent disease that poses a significant threat to human health, and the exploration of highly efficient and low-toxicity anticancer drugs remains an active area of research. Leveraging the cell-penetrating and binding capabilities of steroids, along with the multifunctional pharmacological properties of selenocyano groups, novel compounds are being designed and synthesized with the aim of discovering highly efficient and minimally toxic anti-tumor drugs. In the present study, two selenocyano pharmacophores were incorporated into estradiol to synthesize a series of estradiol diselenocyanate derivatives with a 3-selenocyanoalkoxy-17-selenocyanoester structure. The results of antiproliferative activities evaluation demonstrated that the estradiol derivatives with 3-selenocyanobutoxy moiety exhibited potent inhibitory activity against tumor cell proliferation, especially for triple negative breast cancer cell line MDA-MB-231. Their antiproliferative efficacy was significantly superior to that of estradiol analogues with 3-selenocyanooctyloxy and corresponding monoselenocyanate precursors, indicating a synergistic effect upon introduction of the second selenocyano group on cytotoxicity. The <em>IC</em>₅₀ values for compound <strong>4g</strong> against HeLa, HepG-2, and MCF-7 cells were determined as 3.20, 3.17, and 5.41 μM respectively; notably lower than those observed for its corresponding monoselenocyano precursor <strong>3g</strong> which showed <em>IC</em>₅₀ values of 15.12, 16.09, and 9.44 μM, respectively. Remarkably, the <em>IC</em>₅₀ of compound <strong>4e</strong> against MDA-MB-231 cells is only 5.04 μM and exhibited significant inhibitory activity against MDA-MB-231 zebrafish xenograft tumors. The inhibition of these compounds on tumor cell proliferation was attributed to induction of apoptosis in these cells. Thus, the estradiol diselenocyanate compounds investigated herein hold great potential as novel antitumor drugs, and warrant further investigation.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106771"},"PeriodicalIF":2.7,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924083","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":"G protein-coupled estrogen receptor reduces the breast cancer cell survival by regulating the IRE1α/miR-17-5p/TXNIP pathway","authors":"Maryam Mohammad-Sadeghipour ,&nbsp;Mohammad Hadi Nematollahi ,&nbsp;Maryam Sahebazzamani ,&nbsp;Hassan Ahmadinia ,&nbsp;Mohammad Reza Hajizadeh ,&nbsp;Mehdi Mahmoodi ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.jsbmb.2025.106770","DOIUrl":"10.1016/j.jsbmb.2025.106770","url":null,"abstract":"<div><div>This study aimed to explore whether GPER can induce the UPR response in the SKBR3 cell line through ER and IREα activation, and to assess whether this response leads to cell survival or cell death. Additionally, the study sought to evaluate the impact of this response on cell behaviors such as apoptosis, migration, and drug resistance. To activate the UPR and induce ER stress, we treated the MCF10A cell line with 0.5 µg/ml TUN for 24 and 48 h. The expression levels of XBP-1 and C/EBP homology protein (CHOP) genes (ER stress markers) were measured using the qRT-PCR technique. The MCF10A + TUN cell line was used as a positive control. To determine the optimal doses of G₁ and tamoxifen (TAM), we evaluated GPER expression using qRT-PCR analysis. Cells were then treated with various doses of G₁ (1000 nM), G₁₅ (1000 nM), and TAM (2000 nM), both individually and in combination (G₁ + G₁₅, TAM + G₁₅, G₁ + TAM), for 24 and 48 h. We measured the expression of GPER, IRE1α, MiR-17-5p, TXNIP, ABCB1, and ABCC1 genes. Apoptosis was assessed <em>via</em> flow cytometry, and cell migration was examined using the wound-healing assay. Our results demonstrated that GPER activation by G₁ and TAM significantly increased IRE1α expression in SKBR3 cells. This activation, through its RIDD activity, cleaved miR-17-5p and initiated the UPR death response. The upregulation of the TXNIP gene expression enhanced apoptosis and chemotherapy sensitivity while decreasing cell migration. Interestingly, these effects were notably reversed by G₁₅ treatment. In summary, the GPER/IRE1α/miR-17-5p/TXNIP axis plays a key role in the UPR pro-death response, promoting programmed cell death, reducing migration, and decreasing drug resistance in SKBR3 cells.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106770"},"PeriodicalIF":2.7,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937144","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":"Steroid hormones in pain: Mechanistic underpinnings and therapeutic perspectives","authors":"Xinying Zhang ,&nbsp;Xiaolin Yang ,&nbsp;Yawei Ji ,&nbsp;Yidong Xu ,&nbsp;Yongjiu Ji ,&nbsp;Chenqi Jiang ,&nbsp;Suwan Hu ,&nbsp;Chun Yang","doi":"10.1016/j.jsbmb.2025.106769","DOIUrl":"10.1016/j.jsbmb.2025.106769","url":null,"abstract":"<div><div>Pain is a complex sensory and emotional experience that severely affects an individual's quality of life and health status. Steroid hormones, as important regulatory substances in the human body, are extensively involved in various physiological and pathological processes. In recent years, remarkable progress has been made in the research of steroid hormones in the field of pain. They play a crucial role in the occurrence, development, and treatment of pain. This review comprehensively elaborates on the roles and therapeutic mechanisms of steroid hormones in pain, explores the performances of glucocorticoids, mineralocorticoids, sex hormones, etc. in different pain models, as well as the molecular mechanisms by which they regulate pain through genomic and non-genomic effects, aiming to provide a theoretical basis for the clinical treatment of pain.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"251 ","pages":"Article 106769"},"PeriodicalIF":2.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906369","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}