Journal of Steroid Biochemistry and Molecular Biology最新文献

{"title":"Integrin αVβ3 mediates estrogen to enhance osteoblast proliferation, differentiation, and alleviate OVX-induced postmenopausal osteoporosis","authors":"Changshun Chen ,&nbsp;Rongjing Chen ,&nbsp;Jinyi Gu ,&nbsp;Fei Yang ,&nbsp;Lei Wen ,&nbsp;Zirui Liu ,&nbsp;Chenhui Yang ,&nbsp;Bin Geng ,&nbsp;Yayi Xia","doi":"10.1016/j.jsbmb.2025.106800","DOIUrl":"10.1016/j.jsbmb.2025.106800","url":null,"abstract":"<div><div>Estrogen plays a critical role in maintaining bone homeostasis, and its deficiency leads to postmenopausal osteoporosis. This study investigated the role of integrin αVβ3 in estrogen-mediated osteoblast function and its therapeutic potential in osteoporosis. Using CRISPR/Cas9 technology, we established an integrin αvβ3 knockout model in MC3T3-E1 cells and primary mouse osteoblasts. Estradiol was found to significantly upregulate integrin αVβ3 expression in osteoblasts, as confirmed by Western blotting, RT-qPCR, and immunofluorescence. Functional assays, including CCK8, flow cytometry, ALP staining, and ARS staining, demonstrated that estradiol enhanced osteoblast proliferation, migration, and differentiation, whereas these effects were markedly attenuated in integrin αVβ3-deficient cells. In vivo studies using an ovariectomized (OVX) mouse model revealed that AAV9-mediated knockdown of integrin αVβ3 impaired the protective effects of estradiol against bone loss. Molecular docking analysis further supported these findings, showing strong binding affinity between estradiol and integrin αVβ3, with binding scores of −7.4 kcal/mol for integrin αV and −7.3 kcal/mol for integrin β3. These results collectively indicate that integrin αVβ3 is a key mediator of estrogen's osteogenic effects, promoting osteoblast activity and mitigating postmenopausal osteoporosis. Our findings underscore the potential of targeting integrin αVβ3 as a therapeutic strategy for estrogen deficiency-induced bone loss.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106800"},"PeriodicalIF":2.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195108","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":"Inhibition of brain human steroid 5α-reductase 1 by dithiocarbamates: A Comprehensive enzymatic and structural analysis","authors":"Binbin Lu ,&nbsp;Qian Zhang ,&nbsp;Hang Lin ,&nbsp;Shaowei Wang ,&nbsp;Yang Zhu ,&nbsp;Ren-shan Ge ,&nbsp;Xingwang Li","doi":"10.1016/j.jsbmb.2025.106794","DOIUrl":"10.1016/j.jsbmb.2025.106794","url":null,"abstract":"<div><div>We investigated the inhibitory effects of dithiocarbamates (DTCs) on human steroid 5α-reductase 1 (SRD5A1), an enzyme crucial for the conversion of testosterone or pregnenolone into neuroactive steroids. Utilizing a comprehensive approach that included enzyme assays, molecular docking simulations, and both structure-activity relationship (SAR) and 3D quantitative SAR (3D-QSAR) analyses, we assessed the potency and interaction mechanisms of DTCs with SRD5A1 in human SF126 cells. Our results demonstrated that zinc dibutyldithiocarbamate, disulfiram, ferbam, thiram, and ziram displayed significant inhibitory activity against SRD5A1, with IC₅₀ values of 1.10, 1.62, 2.31, 1.74, and 1.84 μM, respectively. Kinetic studies indicated that these compounds function as mixed inhibitors, suggesting a multifaceted interaction with the enzyme's active site. These DTCs effectively penetrated the cell membrane of SF126 cells to inhibit SRD5A1 at ≥ 5 μM. Molecular docking analyses revealed that these compounds interacted with a distinct domain located between the NADPH and testosterone binding sites of SRD5A1, primarily through sulfur bonds, which are a fundamental component of the DTC structure. Experimental validation of the inhibitory mechanism was achieved by demonstrating that the co-incubation of dithiothreitol, a sulfhydryl-reducing agent, significantly reversed the inhibitory effects of zinc dibutyldithiocarbamate and thiram. SAR analysis revealed a negative correlation between LogP, molecular weight, and IC₅₀ values, and a positive correlation between LogS, lowest binding energy, and IC₅₀ values. The 3D-QSAR analysis further indicated that hydrogen bond acceptor and hydrophobic region capabilities significantly contribute to the primary inhibition. In conclusion, this research significantly advances our understanding of the SAR of sulfur-containing DTCs as inhibitors of human SRD5A1, providing valuable insights for identifying toxicity of DTCs targeting this enzyme.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106794"},"PeriodicalIF":2.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210188","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":"Enhanced bactericidal activity of selenosteroid complexes with zinc, copper, and cobalt against resistant bacterial strains","authors":"Marta Malinowska ,&nbsp;Sławomir Wojtulewski ,&nbsp;Joanna Wysocka ,&nbsp;Damian Zarzecki ,&nbsp;Karolina H. Markiewicz ,&nbsp;Beata Kalska-Szostko ,&nbsp;Urszula Wnorowska ,&nbsp;Robert Bucki ,&nbsp;Izabella Jastrzebska","doi":"10.1016/j.jsbmb.2025.106793","DOIUrl":"10.1016/j.jsbmb.2025.106793","url":null,"abstract":"<div><div>Let's enhance the activity of selenosteroids! For this purpose, we have obtained a new class of metal complexes with the steroid β-hydroxy-phenylselenide as a model ligand using a simple and efficient methodology. The obtained compounds were characterised by ¹H and ⁷⁷Se nuclear magnetic resonance spectroscopy, infra-red spectroscopy, mass spectra, X-ray diffraction and thermogravimetric analysis. The bactericidal activity of the complexes against <em>Pseudomonas aeruginosa</em> and <em>Staphylococcus aureus</em> was then evaluated using a standard killing assay. The results showed that the copper and cobalt complexes with selenosteroid exhibited significant bactericidal activity against <em>P. aeruginosa</em>. The presented synthetic method shows potential for obtaining compounds that may be effective in treating infections caused by these clinically relevant bacterial strains.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"253 ","pages":"Article 106793"},"PeriodicalIF":2.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200695","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":"7-Ketocholesterol: A pathogenic oxysterol in atherosclerosis and lysosomal storage disorders – Molecular insights and clinical implications","authors":"Thanga Yogeshwaran Gajendran ,&nbsp;Nila Ganamurali ,&nbsp;Sarvesh Sabarathinam","doi":"10.1016/j.jsbmb.2025.106797","DOIUrl":"10.1016/j.jsbmb.2025.106797","url":null,"abstract":"<div><div>One important oxysterol produced by the autoxidation of cholesterol is 7-Ketocholesterol (7-KC), which plays a major role in both physiological and pathological processes. The pathogenic functions of 7-KC are reviewed in this study, with particular attention paid to its molecular processes and its participation in a number of diseases, such as lysosomal storage disorders (LSDs) and atherosclerosis. Through processes like oxidative stress, phospholipidosis, and lysosomal accumulation, 7-KC causes cytotoxicity, which in turn results in cell death. In atherosclerosis, it has a role in plaque instability, foam cell production, and endothelial dysfunction. Furthermore, 7-KC intensifies lysosomal dysfunction in LSDs, hastening the course of the illness. Additionally, 7-KC causes oxiapoptophagy, a kind of cell death marked by the co-occurrence of autophagy, apoptosis, and oxidative stress. By influencing inflammatory signalling, Reactive oxygen species (ROS) generation, and lipid peroxidation, 7-KC increases cellular damage and speeds up the aetiology of disease. This study clarifies how 7-KC contributes to endothelial dysfunction, atherosclerosis, and LSDs by highlighting its dual roles as a pathogenic molecule and a possible therapeutic target.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106797"},"PeriodicalIF":2.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184982","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":"Geographical differences in 25(OH)D reference intervals","authors":"Efsane Yavuz ,&nbsp;Mustafa Örkmez ,&nbsp;Mehmet Akif Bildirici ,&nbsp;İsmet Gamze Bozdayı ,&nbsp;Murat Usta","doi":"10.1016/j.jsbmb.2025.106790","DOIUrl":"10.1016/j.jsbmb.2025.106790","url":null,"abstract":"<div><div>Vitamin D deficiency has become a widespread public health problem worldwide. In recent years,numerous studies have been conducted to define the reference range for 25(OH)D.The aim was to determine the reference interval of Vitamin D and its metabolically related parameters, including PTH, Ca, P and ALP,using direct and indirect methods for the Southeastern Anatolia and Black Sea regions,which differ significantly in terms of geographical location and dietary habits that greatly influence Vitamin D levels. In the direct method, reference ranges were calculated using non-parametric methods according to CLSI EP28-A3 guidelines. In the indirect method, reference ranges were determined after data filtration and calculated using the Bhattacharya method<strong>.</strong> In the direct method, the reference interval for 25(OH)D were found to be 8.03–29.44 ng/mL in summer and 5.55–23.07 ng/mL in winter for the Southeastern Anatolia Region, and 6.34–29.69 ng/mL in summer and 6.28–27.34 ng/mL in winter for the Black Sea Region. In the indirect method, the reference interval for 25(OH)D were determined as 7.24–41.69 ng/mL in the Southeastern Anatolia Region and 6.17–42.66 ng/mL in the Black Sea Region. The prevalence of severe Vitamin D deficiency in the reference population during the summer and winter seasons was found to be 7.6 % and 30.5 %, respectively, in the Southeastern Anatolia Region, and 24.1 % and 22.1 %, respectively, in the Black Sea Region. This study has shown that despite variations in reference ranges for laboratory tests due to societal, regional, and seasonal differences, the levels of 25(OH)D were lower than the recommended reference ranges.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106790"},"PeriodicalIF":2.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169277","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":"Microbial modulation of digoxin bioavailability: A pharmacomicrobiome perspective on Eggerthella lenta’s role in steroid-like drug metabolism and precision therapeutics","authors":"Nila Ganamurali ,&nbsp;Sarvesh Sabarathinam","doi":"10.1016/j.jsbmb.2025.106792","DOIUrl":"10.1016/j.jsbmb.2025.106792","url":null,"abstract":"<div><div>Digoxin is a cardiac glycoside used to treat heart failure and atrial fibrillation, but its narrow therapeutic index makes precise dosing critical. The effectiveness of digoxin is influenced by individual variations in drug metabolism, with recent studies showing that gut microbiota, particularly <em>Eggerthella lenta (E. lenta)</em>, plays a key role. <em>E. lenta</em> can convert digoxin into its inactive form, dihydrodigoxin, potentially reducing its therapeutic efficacy. This paper explores how <em>E. lenta</em> affects the biotransformation of digoxin and other drugs like L-dopa and resveratrol. The aim is to investigate how the presence of <em>E. lenta</em> in the gut influences drug metabolism and therapeutic outcomes. The review also examines the broader implications of microbiome-driven drug interactions and highlights the need for precision dosing strategies based on an individual’s microbiome composition which is also essential for patients with high <em>E. lenta</em> colonization. Further research into microbiome-driven drug and sterol interactions is needed to optimize treatment strategies, ensuring personalized and effective patient care.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106792"},"PeriodicalIF":2.7,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134205","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":"Tea polyphenols and EGCG induce preeclampsia-like symptoms by reducing 2-methoxyestradiol","authors":"Yi Duan,&nbsp;Chen Jin,&nbsp;Jiaqi Wang,&nbsp;Pan Wang","doi":"10.1016/j.jsbmb.2025.106789","DOIUrl":"10.1016/j.jsbmb.2025.106789","url":null,"abstract":"<div><div>Preeclampsia (PE), a severe pregnancy-specific disorder, poses significant health risks to both mothers and fetuses. Certain dietary habits, such as tea consumption, may affect the activity of enzymes involved in hormone metabolism, leading to alterations in the levels of important pregnancy-related hormone metabolites, such as 2-methoxyestradiol (2-MeO-E₂), which may contribute to the development of PE. To investigate the effect of tea intake on pregnancy, we conducted both <em>in vivo</em> and <em>in vitro</em> experiments. Pregnant rats were administered tea polyphenols and epigallocatechin gallate (EGCG) by gavage starting from pregnancy day 10. We found that tea polyphenols and EGCG intake during pregnancy induced PE-like symptoms in the rats such as hypertension, proteinuria and growth restriction of fetuses. These symptoms could be rescued by cotreatment of 2-MeO-E_2. Notably, the levels of the estrogen metabolite 2-MeO-E₂ in rat blood were significantly reduced, and the activity of the enzyme responsible for its metabolism, catechol-O-methyltransferase (COMT), was also inhibited. Furthermore, EGCG impaired the migration ability of HTR8/SVneo cells, which could be alleviated by 2-MeO-E₂ supplementation. These findings indicate that tea polyphenols intake during pregnancy can cause PE-like symptoms by inhibiting COMT activity and production of 2-MeO-E₂.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106789"},"PeriodicalIF":2.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123933","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":"Changes in vitamin D biomarkers across pregnancy and by maternal BMI: A secondary analysis of data and biospecimens from the National Children’s Study","authors":"Skylar Mercer ,&nbsp;Xianyan Chen ,&nbsp;Biplav B. Tiwari ,&nbsp;Alex Anderson ,&nbsp;Sheree L. Boulet ,&nbsp;Janani Rajbhandari ,&nbsp;Sina Gallo","doi":"10.1016/j.jsbmb.2025.106791","DOIUrl":"10.1016/j.jsbmb.2025.106791","url":null,"abstract":"<div><div>Obesity during pregnancy is associated with increased risk for vitamin D deficiency in both the mother and offspring. Free or unbound 25-hydroxyvitamin D (25(OH)D) is the biologically active form as compared to total 25(OH)D, which may be important in the assessment of vitamin D status during conditions like pregnancy where vitamin D binding protein (VDBP) is affected. Little is known about how pre-pregnancy BMI affects changes in vitamin D markers during pregnancy. This is a secondary analysis of data and biospecimens from the 2009–2014 National Children’s Study (NCS). The current analysis included 50 participants (50 % normal weight [18.5 ≥BMI&lt;25 kg/m²] and 50 % overweight/obese [BMI≥25 kg/m²]), recruited across four US Census regions (Northeast, South, West, and Midwest), with serum samples available from three time points during pregnancy: 1st half (&lt;25 weeks), 2nd half (&gt;25 weeks) and birth. Total 25(OH)D was quantified via liquid chromatography-tandem mass spectrometry (LC-MS/MS), and commercially available assays were used to measure free 25(OH)D and VDBP. Percent free 25(OH)D was calculated as <span><math><mrow><mfrac><mrow><mi>free</mi><mn>25</mn><mrow><mfenced><mrow><mi>OH</mi></mrow></mfenced></mrow><mi>D</mi></mrow><mrow><mi>total</mi><mn>25</mn><mrow><mfenced><mrow><mi>OH</mi></mrow></mfenced></mrow><mi>D</mi></mrow></mfrac><mi>x</mi><mn>100</mn></mrow></math></span>. Linear mixed effect models, including quadratic gestational age term were employed to exam the change in vitamin D metabolites by quadratic gestational age, as well as interactions with pre-pregnancy BMI and season of birth. A positive linear trend was observed for total 25(OH)D levels across gestation (p = 0.002), while quadratic relationships were observed for both VDBP (p &lt; 0.001) and % free 25(OH)D (p = 0.001). A significant interaction was observed between gestational age and season of birth for total 25(OH)D (p &lt; 0.001) and free 25(OH)D (p = 0.006). Furthermore, the interactive effect of gestational age and pre-pregnancy BMI was statistically significant for both total 25(OH)D (p = 0.002) and % free 25(OH)D (p = 0.007). Our results suggest that among a sample of US women both season of birth and maternal pre-pregnancy BMI affected changes in vitamin D metabolites across pregnancy. The effects of maternal BMI on changes in total 25(OH)D and % free 25(OH)D across pregnancy suggest maternal obesity may differentially affect vitamin D metabolism in pregnancy. Future research is necessary to compare differences in vitamin D metabolism among obesity affected pregnancies as compared to healthy-weight counterparts.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106791"},"PeriodicalIF":2.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133325","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":"Confirmation of a novel, stable estrogen metabolite, as 5a,6a-epoxy-estrone sulfate in stallion blood by LC-MS/MS","authors":"James I. Raeside ,&nbsp;Heather L. Christie ,&nbsp;Tracey Chenier ,&nbsp;Dyanne Brewer ,&nbsp;Armen Charchoglyan","doi":"10.1016/j.jsbmb.2025.106788","DOIUrl":"10.1016/j.jsbmb.2025.106788","url":null,"abstract":"<div><div>Mass spectrometry (MS) has become pivotal for accurately delineating intricate molecular structures for steroids present in minute quantities within biological samples. This study utilized liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) to identify and characterize a ‘new’ estrogen metabolite, 5α,6α-epoxy-estrone sulfate, in stallion serum from three animals. The estrogen structure was predicted previously using radiolabeled steroids. HRMS/MS, in combination with a seamless sample preparation involving liquid-liquid extraction and chromatographic separation, enabled accurate mass spectrometric identification of the target metabolite. A distinct chromatographic peak corresponding to the metabolite displayed a fragmentation pattern consistent with its predicted structure. Fragment ions at <em>m/z</em> 79.9 and 285.1 resulting from precursor ion <em>m/z</em> 365.5 [M-H]^{<strong>-</strong>} suggested the presence of a sulfated group and epoxy form of estrone, with an additional oxygen atom when compared with those for a reference standard of estrone sulfate. The assignment of other fragment ions from the target ion further elucidated the predicted structure. Evidence for a structure unique from any other estrogen metabolite on record was demonstrated on two different LC-QTOF instruments. Its identification in the blood circulation ensures distribution throughout the body. The potential significance for future physiological/pathological investigations is discussed.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106788"},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129609","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":"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}