The Journal Of Steroid Biochemistry And Molecular Biology[JOURNAL]
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200 papers
Identification of amh and its potential signaling pathway involved in the ovary development in the largemouth bass (Micropterus salmoides).
Liu H, Wang Y, Guo Q … +9 more , Tian X, Ma X, Zhang M, Shi X, Ma W, Zhang J, Xu R, Li X, Kong X
J Steroid Biochem Mol Biol · 2025 Oct · PMID 40499662 · Publisher ↗
Anti-müllerian hormone (AMH), a member of the TGF-β family, plays a pivotal role in ovarian development by binding to its specific receptor, AMHR2. However, the function of amh/amhr2 pathway in fish ovarian development r...
Anti-müllerian hormone (AMH), a member of the TGF-β family, plays a pivotal role in ovarian development by binding to its specific receptor, AMHR2. However, the function of amh/amhr2 pathway in fish ovarian development remains poorly understood. To elucidate its regulatory mechanism in largemouth bass, we identified amh and amhr2 genes from the largemouth bass genome and analyzed their expression patterns across different tissues and ovarian developmental stages. The results showed that amh was mainly expressed in the testis, ovary, brain and pituitary, while amhr2 was highly expressed in the testis and ovary. In vitro treatment of ovarian follicles with recombinant Amh protein increased GVBD rates of cultured oocytes, and the expression levels of amh receptors (amhr2, alk2, alk3 and alk6) and smad signaling pathway (smad1, smad5, smad8 and smad4) were significantly upregulated. Additionally, the expression of key steroidogenesis (stAR, 17βhsd, cyp17a2, cyp19a1a) and oocyte maturation-related genes (cyclin B, cdk1) were also increased. Conversely, inhibition of Amhr1 with Compound C attenuated Amh-induced upregulation of Amh receptors, SMADs, and steroidogenic genes. These findings provide novel insights into the molecular mechanisms by which the amh/amhr2 signaling pathway regulates ovarian development in largemouth bass, highlighting its role in follicular maturation and steroidogenesis.
Vitamin D status in young adults with cystic fibrosis on highly effective CFTR modulator therapy.
Cobb C, Alvarez JA, Hunt WR … +3 more , Daley T, Bai S, Tangpricha V
J Steroid Biochem Mol Biol · 2025 Oct · PMID 40484046 · Publisher ↗
Vitamin D deficiency is a common pathology in people with cystic fibrosis (PwCF) due to the malabsorption of fat-soluble vitamins. Vitamin D plays an integral role in bone health and lung immunity; therefore, treating de...
Vitamin D deficiency is a common pathology in people with cystic fibrosis (PwCF) due to the malabsorption of fat-soluble vitamins. Vitamin D plays an integral role in bone health and lung immunity; therefore, treating deficiencies is a clinical priority in PwCF. Highly effective modulator therapy (HEMT) improves the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein that is altered in PwCF, resulting in improved lung function and fat absorption. However, the impact of HEMT on restoring vitamin D status, a fat-soluble vitamin, has not been fully elucidated. We retrospectively examined serum 25-hydroxyvitamin D (25(OH)D) up to ten years prior in 89 young adults with CF classified based on current HEMT use (yes or no). We used two-way ANOVA to evaluate trends in both groups. Both HEMT users (n = 68) and HEMT non-users (n = 21) on average exhibited decreased serum 25(OH)D levels over ten years (-14.2 ng/mL (SI 35.4 nmol/L) and -14 ng/mL (SI 34.9 nmol/L) respectively), with no difference in change between the two groups (p = 0.44). This suggests that HEMT may not correct vitamin D status in PwCF. Further large scale prospective studies are needed to comprehensively investigate the relationship between vitamin D and HEMT.
Vitamin D deficiency: A risk factor for antibody decline in COVID-19?
Bohl LP, Breser ML, Aguirre GE … +7 more , Capello MI, Menichetti GI, Tiraboschi G, Rodríguez-Berdini L, Isaac P, Ángeles Fernández ML, Porporatto C
J Steroid Biochem Mol Biol · 2025 Oct · PMID 40484045 · Publisher ↗
Vaccination was critical in controlling the transmission of SARS-CoV-2 during the COVID-19 pandemic. Nevertheless, immune responses are also influenced by nutritional and endocrine factors, particularly vitamin D, whose...
Vaccination was critical in controlling the transmission of SARS-CoV-2 during the COVID-19 pandemic. Nevertheless, immune responses are also influenced by nutritional and endocrine factors, particularly vitamin D, whose deficiency has been linked to an increased risk and severity of respiratory infections. This study aimed to assess the impact of 25-hydroxyvitamin D (25(OH)D) levels on the humoral immune response to SARS-CoV-2, as measured by specific immunoglobulin G (IgG) antibody levels. Associations with other factors were also explored, including symptoms, pre-existing conditions, COVID-19 history, vaccination status, and medication use during the course of infection. A longitudinal study was conducted with 131 adult patients from Villa del Rosario (Argentina) who tested positive for SARS-CoV-2 between August and December 2021. Data on weight, age, height, gender, symptoms, pre-existing conditions, vitamin D sources, and COVID-19 history were collected upon diagnosis, as well as 30 and 180 days post-diagnosis. Eighty-five percent of the patients experienced mild COVID-19; 65 % had low vitamin D levels, and individuals with pre-existing conditions had significantly lower 25(OH)D levels. The highest antibody levels were observed one month after diagnosis. Vaccinated patients exhibited higher specific antibody levels than unvaccinated ones. Those who used palliative medication for symptom control had lower levels of specific antibodies. Finally, antibody levels decreased significantly between day 30 and day 180 post-diagnosis in patients with vitamin D deficiency. These findings emphasize the importance of maintaining adequate vitamin D levels for sustained immune responses, and highlight the role of vaccination in enhancing immune protection against COVID-19.
Frontiers in steroid research: Steroid congress 2023.
Penning TM, Adamski J
J Steroid Biochem Mol Biol · 2025 Oct · PMID 40482785 · Publisher ↗
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Anti-androgenic and anti-proliferative properties of methanolic leaf extract of Allamanda cathartica Linn. in adult mouse testis: Evidences from in vivo and in silico studies.
Raman R, Kaur R, Kulkarni S … +5 more , Joshi D, Parkash J, Thareja S, Sarkar D, Singh SK
J Steroid Biochem Mol Biol · 2025 Oct · PMID 40482784 · Publisher ↗
Dysregulation in androgen production causes a variety of clinical disorders like male pattern baldness, hirsutism, acne vulgaris, benign prostatic hyperplasia, prostate cancer and polycystic ovarian syndrome. Although th...
Dysregulation in androgen production causes a variety of clinical disorders like male pattern baldness, hirsutism, acne vulgaris, benign prostatic hyperplasia, prostate cancer and polycystic ovarian syndrome. Although the common synthetic drugs used to treat these diseases have many side effects, there is growing demand for alternative and herbal therapies. Allamanda cathartica Linn. (family, Apocynaceae) is traditionally used to treat variety of diseases because of its hepatoprotective, antidiabetic, anti-inflammatory, antitumor and antimicrobial properties. However, the effects of Allamanda leaves on testosterone production still remain elusive. The present study aims to elucidate the effect and possible mode(s) of action of the methanolic leaf extract of A. cathartica (MLEAC) on androgen biosynthesis and germ cell proliferation in adult mouse testis. Adult male C57BL/6J mice were orally administered MLEAC (150 and 300 mg/kg body weight/day) or distilled water (controls) for 42 days. MLEAC treatment caused non-uniform degenerative changes in the histoarchitecture of testis. The treatment also had negative impact on serum testosterone level with downregulation of the expressions of major steroidogenic proteins (StAR, CYP11A1, 3β-and 17β-HSD3). Flow cytometry and immunohistochemical analyses showed impaired gem cell proliferation in MLEAC-treated mice testes. The GC-MS method identified 20 phytocompounds in MLEAC. The in silico study further revealed that GC-MS-derived phytochemicals have the potential to bind with major steroidogenic proteins in testis. MLEAC treatment thus causes suppression of germ cell proliferation via downregulation of testosterone production. Keeping in view the traditional use of Allamanda, the present findings may prove helpful in the search of a plant-based anti-androgenic compound.
Untangling hidden players of PCOS: From transcriptomics to key biomarkers using WGCNA, LASSO and ROC analysis.
Senthilkumar H, Arumugam M
J Steroid Biochem Mol Biol · 2025 Oct · PMID 40480394 · Publisher ↗
Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder characterized by hormonal imbalance, inflammation and insulin resistance. This study utilized a comprehensive RNA-Seq workflow to uncover the...
Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder characterized by hormonal imbalance, inflammation and insulin resistance. This study utilized a comprehensive RNA-Seq workflow to uncover the molecular mechanisms underlying PCOS. Data were retrieved from the NCBI- Sequence Read Archive [SRA] repository, followed by quality assessment using FastQC and Trimmomatic trimming. Reads were aligned to the GRCh38 genome using HISAT2 and differential expression analysis was performed by DESeq2 in R, identifying 395 significant DEGs (268 upregulated, 127 downregulated). Gene ontology (GO) analysis revealed dysregulated biological processes including activation of protein kinase activity, telomerase capping, protein serine/ threonine kinase activity and MAP kinase kinase activity, while KEGG pathway analysis highlighted key signaling pathways such as MAPK signaling, Ras signaling, and GnRH signaling. Weighted gene co-expression network analysis (WGCNA) identified modules associated with PCOS traits and Protein-Protein Interaction (PPI) network analysis identified 20 hub genes. Through Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, five key predictor genes - PRKACA, SREBF2, MAPT, EHMT1, and JUP were identified, highlighting their critical roles in the pathogenesis of PCOS. The prognostic value of these genes was further validated by receiver operating characteristics (ROC) curve analysis, which showed a high area under the curve (AUC) of 0.89. This strong discriminatory power between PCOS and healthy groups highlights the potential of these biomarkers as reliable indicators for diagnosing and understanding the disease. The results highlight the therapeutic and diagnostic potential of these biomarkers and pave the way for precision medicine approaches in PCOS treatment.
Evaluation of reference ranges of four circulating sex steroids from dried blood spots in women aged 18-40 years.
Wang Y, Davis SR, Gialouris J … +2 more , Desai R, Handelsman DJ
J Steroid Biochem Mol Biol · 2025 Oct · PMID 40473059 · Publisher ↗
Capillary dried blood spot collection offers an excellent less invasive alternative to serum or plasma collection by venesection. This study aimed to generate reference ranges for four sex steroids in capillary whole blo...
Capillary dried blood spot collection offers an excellent less invasive alternative to serum or plasma collection by venesection. This study aimed to generate reference ranges for four sex steroids in capillary whole blood samples collected from healthy premenopausal women as dried blood spots as a screening method to detect disorders of sex development. Using this method we evaluated variations according to age, body mass index, menstrual cycle, and hormonal contraceptive use. This cross-sectional, community-based study included 120 healthy premenopausal women aged 18-40 years, not pregnant or breastfeeding. Whole blood testosterone (T), androstenedione (A4), 17α hydroxyprogesterone (17OHP), and progesterone (P4) were measured by liquid chromatography-tandem mass spectrometry (LCMS) from dried filter paper blood spots. The median (95 % confidence limits) for T were 0.75 (0.28, 2.20) nmol/L, A4 2.69 (1.02, 6.03) nmol/L, 17OHP 1.62 (0.32, 8.52) nmol/L and P4 0.65 (0.18, 41.0) nmol/L. Age by 5-year interval was associated with a progressive reduction in A4 but not for other steroids. Menstrual variation was evident for 17OHP and P4 with increases in luteal phase with a small mid-cycle peak for A4 but no other consistent changes. All sex steroid concentrations were significantly lower in participants taking a systemic hormonal contraceptive (combined oral contraceptive or etonogestrel implant). None of the sex steroid concentrations varied significantly with body mass index. These data provide reference ranges for whole blood T, A4, 17OHP and P4 measured by LCMS from dried blood spots from healthy young adult premenopausal women. Small but significant variations were evident according to age, hormonal contraceptive use and menstrual cycle phase.
Reduced and rearranged metabolite structures after metandienone administration: New promising metabolites for potential long-term detection.
Steff J, Molaioni F, Schlörer N … +4 more , de la Torre X, Bureik M, Botrè F, Parr MK
J Steroid Biochem Mol Biol · 2025 Oct · PMID 40473058 · Publisher ↗
Metandienone (MD) is a representative of the group of anabolic androgenic steroids and is commonly used in professional and amateur sports despite being a banned substance by the World Anti-Doping Agency (WADA). Metaboli...
Metandienone (MD) is a representative of the group of anabolic androgenic steroids and is commonly used in professional and amateur sports despite being a banned substance by the World Anti-Doping Agency (WADA). Metabolites of MD show high structural similarity to related anabolic androgenic steroids (AAS) such as dehydrochloromethyltestosterone (DHCMT). This led to the hypothesis that metabolites of MD with structures similar to long-term metabolites of DHCMT may be detectable. Therefore, a human administration study of MD was carried out and analyzed with the focus on metabolite structures with partly or fully reduced A-rings and eventually with rearranged D-rings with 17ξ-hydroxymethyl-17ξ-methyl substructures. Synthesized diastereomeric reference material allowed the establishment of a confident identification and characterization of excreted targeted compounds by gas chromatography-mass spectrometry. In this way, the excretion of inter alia 17α-methyl-5β-androstane-3α,17β-diol (T3), 17β-methyl-5β-androstane-3α,17α-diol (T7), 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol (N3), 17α-hydroxymethyl-17β-methyl-18-nor-5β-androsta-1,13-dien-3α-ol (E3) and 17,17-dimethyl-18-nor-5β-androst-13-en-3α-ol (3α5βnorTHMT) was confirmed. Excretion curves of previously known and newly discovered metabolites enabled the assessment of the relationship between the chemical structure and the time of excretion. In addition to further assembling the picture of human metabolism of AAS with newly discovered metabolites, the detection of E3 allows the presumption to be a promising future candidate for a new long-term marker in anti-doping analyses with indications for an increased detection window.
Integrin αVβ3 mediates estrogen to enhance osteoblast proliferation, differentiation, and alleviate OVX-induced postmenopausal osteoporosis.
Chen C, Chen R, Gu J … +6 more , Yang F, Wen L, Liu Z, Yang C, Geng B, Xia Y
J Steroid Biochem Mol Biol · 2025 Sep · PMID 40466876 · Publisher ↗
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...
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.
Vitamin D promotes wound healing in aged skin by modulating inflammation, angiogenesis, and EMT via the Hippo pathway.
Gong Y, Ren Y, Jia N … +3 more , Zhang X, Li Y, Zhi X
J Steroid Biochem Mol Biol · 2025 Sep · PMID 40466431 · Publisher ↗
Age-related impairment in skin wound healing represents a significant healthcare challenge. Vitamin D (VD) has been shown to enhance diabetic wound healing. However, its therapeutic potential in age-related wound healing...
Age-related impairment in skin wound healing represents a significant healthcare challenge. Vitamin D (VD) has been shown to enhance diabetic wound healing. However, its therapeutic potential in age-related wound healing deficits remains unexplored. Here, we investigated VD's impact on wound healing in aged mice and the underlying mechanisms. Twelve-month-old C57BL/6 J mice received VD supplementation for 3 months before full-thickness excisional wounds were created. Wound healing was evaluated through multiple aspects, including inflammation, angiogenesis, epithelial-mesenchymal transition (EMT), and the Hippo signaling pathway. We also examined responses to 1α,25(OH)D in HaCaT cells. VD supplementation significantly accelerated wound closure by modulating several key processes. It promoted inflammation resolution by suppressing pro-inflammatory factors (IL-6, TNF-α), elevating IL-10 levels, and facilitating M1-to-M2 macrophage polarization. VD enhanced angiogenesis through increased CD31-positive vessel formation and upregulation of angiogenic factors (VEGF, VEGFR2, PDGF). It also promoted EMT, as evidenced by reduced epithelial markers, increased mesenchymal markers, and upregulated EMT-related transcription factors. Mechanistically, VD inactivated the Hippo pathway, shown by downregulated Mst1 and Lats1 expressions, decreased p-YAP protein levels, increased YAP and TAZ protein levels, and upregulated target gene expressions (Cyr61). In vitro studies using HaCaT cells confirmed that 1α,25(OH)D promoted cell migration and EMT through Hippo pathway modulation, as these effects were abolished after verteporfin (YAP inhibitor) treatment. Our findings demonstrated that VD supplementation effectively accelerated wound healing in aged skin by modulating inflammation, increasing angiogenesis, and promoting EMT via the Hippo pathway, suggesting VD as a promising therapeutic strategy for managing age-related wound healing deficits.
Inhibition of brain human steroid 5α-reductase 1 by dithiocarbamates: A Comprehensive enzymatic and structural analysis.
Lu B, Zhang Q, Lin H … +4 more , Wang S, Zhu Y, Ge RS, Li X
J Steroid Biochem Mol Biol · 2025 Oct · PMID 40456370 · Publisher ↗
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 comp...
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 IC 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 IC values, and a positive correlation between LogS, lowest binding energy, and IC 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.
7-Ketocholesterol: A pathogenic oxysterol in atherosclerosis and lysosomal storage disorders - Molecular insights and clinical implications.
Gajendran TY, Ganamurali N, Sabarathinam S
J Steroid Biochem Mol Biol · 2025 Sep · PMID 40451337 · Publisher ↗
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...
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.
Enhanced bactericidal activity of selenosteroid complexes with zinc, copper, and cobalt against resistant bacterial strains.
Malinowska M, Wojtulewski S, Wysocka J … +6 more , Zarzecki D, Markiewicz KH, Kalska-Szostko B, Wnorowska U, Bucki R, Jastrzebska I
J Steroid Biochem Mol Biol · 2025 Oct · PMID 40451336 · Publisher ↗
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 ob...
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 H and Se nuclear magnetic resonance spectroscopy, infra-red spectroscopy, mass spectra, X-ray diffraction and thermogravimetric analysis. The bactericidal activity of the complexes against Pseudomonas aeruginosa and Staphylococcus aureus was then evaluated using a standard killing assay. The results showed that the copper and cobalt complexes with selenosteroid exhibited significant bactericidal activity against P. aeruginosa. The presented synthetic method shows potential for obtaining compounds that may be effective in treating infections caused by these clinically relevant bacterial strains.
Geographical differences in 25(OH)D reference intervals.
Yavuz E, Örkmez M, Bildirici MA … +2 more , Bozdayı İG, Usta M
J Steroid Biochem Mol Biol · 2025 Sep · PMID 40441313 · Publisher ↗
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...
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. 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.
Microbial modulation of digoxin bioavailability: A pharmacomicrobiome perspective on Eggerthella lenta's role in steroid-like drug metabolism and precision therapeutics.
Ganamurali N, Sabarathinam S
J Steroid Biochem Mol Biol · 2025 Sep · PMID 40425055 · Publisher ↗
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 d...
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 Eggerthella lenta (E. lenta), plays a key role. E. lenta can convert digoxin into its inactive form, dihydrodigoxin, potentially reducing its therapeutic efficacy. This paper explores how E. lenta affects the biotransformation of digoxin and other drugs like L-dopa and resveratrol. The aim is to investigate how the presence of E. lenta 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 E. lenta colonization. Further research into microbiome-driven drug and sterol interactions is needed to optimize treatment strategies, ensuring personalized and effective patient care.
Tea polyphenols and EGCG induce preeclampsia-like symptoms by reducing 2-methoxyestradiol.
Duan Y, Jin C, Wang J … +1 more , Wang P
J Steroid Biochem Mol Biol · 2025 Sep · PMID 40409737 · Publisher ↗
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...
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-E), which may contribute to the development of PE. To investigate the effect of tea intake on pregnancy, we conducted both in vivo and in vitro 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 Notably, the levels of the estrogen metabolite 2-MeO-E 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-E supplementation. These findings indicate that tea polyphenols intake during pregnancy can cause PE-like symptoms by inhibiting COMT activity and production of 2-MeO-E.
Changes in vitamin D biomarkers across pregnancy and by maternal BMI: A secondary analysis of data and biospecimens from the National Children's Study.
Mercer S, Chen X, Tiwari BB … +4 more , Anderson A, Boulet SL, Rajbhandari J, Gallo S
J Steroid Biochem Mol Biol · 2025 Sep · PMID 40409736 · Full text
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(...
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<25 kg/m] and 50 % overweight/obese [BMI≥25 kg/m]), recruited across four US Census regions (Northeast, South, West, and Midwest), with serum samples available from three time points during pregnancy: 1st half (<25 weeks), 2nd half (>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 free25OHDtotal25OHDx100. 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 < 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 < 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.
Strontium regulating lipid metabolism of bovine hepatocytes via SIRT1/SREBPs pathway.
Zeng F, Hu W, Xu H … +4 more , Wang X, Zhao C, Wang Y, Wang J
J Steroid Biochem Mol Biol · 2025 Sep · PMID 40403884 · Publisher ↗
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. Whil...
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.
Confirmation of a novel, stable estrogen metabolite, as 5a,6a-epoxy-estrone sulfate in stallion blood by LC-MS/MS.
Raeside JI, Christie HL, Chenier T … +2 more , Brewer D, Charchoglyan A
J Steroid Biochem Mol Biol · 2025 Sep · PMID 40403883 · Publisher ↗
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 reso...
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 m/z 79.9 and 285.1 resulting from precursor ion m/z 365.5 [M-H] 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.
1,25(OH)D up-regulated mitochondrial dynamics and biogenesis to modulate steroidogenesis in the scent glands of muskrats (Ondatra zibethicus).
Gao Q, Shi K, Shi X … +3 more , Liu Y, Zhang H, Weng Q
J Steroid Biochem Mol Biol · 2025 Sep · PMID 40398522 · Publisher ↗
Vitamin D 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 recep...
Vitamin D 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 D 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 D 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 Cyp27b1, Cyp24a1, Vdr, Mfn1, Opa1, Vdac, Tfam, Pgc1b, Star, Cyp11a1, Cyp17a1, and Cyp19a1 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 (E), and 1,25(OH)₂D₃ of the scent glands were also significantly higher in the breeding season. Additionally, the addition of 1,25(OH)D to the primary scent glandular cells in vitro 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.
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