The Journal Of Steroid Biochemistry And Molecular Biology[JOURNAL]
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200 papers
17 β-Estradiol inhibits GSDME-mediated pyroptosis in ERα-positive breast cancer cells by promoting GSDME promoter methylation.
Pan Y, Li R, Ma H … +8 more , Hu X, Zhao J, Qiao J, Dou X, Wang Y, Zhang Y, Wang X, Wang L
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41386327 · Publisher ↗
Expression of the critical pyroptosis protein gasdermin E (GSDME) has been reported to be regulated by DNA methylation and negatively correlated with the expression of estrogen receptor (ER) in breast cancer tissues, sug...
Expression of the critical pyroptosis protein gasdermin E (GSDME) has been reported to be regulated by DNA methylation and negatively correlated with the expression of estrogen receptor (ER) in breast cancer tissues, suggesting that estrogen-induced target gene methylation may be involved in the regulation of GSDME expression in breast cancer cells. To test this hypothesis, we treated MCF-7 and T47D ER-positive breast cancer cells with 17-β-Estradiol (E), either alone or in combination with selective ERα antagonist AZD9496, selective ERβ antagonist PHTPP, DNA methyltransferase (DNMT) inhibitor RG108, and selective ER degrader Fulvestrant (Ful). Then, GSDME protein and mRNA expression were examined with western blot and RT-qPCR. Pyroptosis was induced by short-wave ultraviolet (UV-C) and detected with morphological observation, lactate dehydrogenase (LDH) release assay, and propidium iodide-Annexin V-FITC fluorescence staining. The methylation status of the GSDME promoter was tested with methylation-specific PCR. The results demonstrated that 100 nM E significantly decreased GSDME protein and mRNA expression in MCF-7 and T47D cells, and significantly inhibited UV-C-induced pyroptosis. AZD9496 but not PHTPP significantly attenuated the down-regulatory effect of E on GSDME expression. E induced DNA methylation in the GSDME promoter region and up-regulated DNMT1 expression. RG108 strengthened UV-C-induced pyroptosis, and Ful reversed the inhibitory effects of E on UV-C-induced pyroptosis of MCF-7 and T47D cells Taken together, our study suggests that E down-regulated GSDME expression in ERα-positive breast cancer by promoting GSDME promoter methylation, and inhibited UV-C-induced pyroptosis.
The effect of endurance training with Maca or ginger on steroidogenesis and antioxidant status of testicular tissue in male rats.
Alsamawi SAA, Nasiri K, Akbari A … +1 more , Fathi R
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41386326 · Publisher ↗
Today's primary approach to enhancing reproductive function involves lifestyle modifications, dietary adjustments, the use of herbal supplements, and regular exercise. In this study, we tried to show that the use of ging...
Today's primary approach to enhancing reproductive function involves lifestyle modifications, dietary adjustments, the use of herbal supplements, and regular exercise. In this study, we tried to show that the use of ginger or Maca supplements along with endurance training can affect reproductive function indicators, including spermatogenesis and steroidogenesis in testicular tissue. Adult male Wistar rats (n = 42, weight: 220 ± 20 g, age: 10-12 weeks) were randomly divided into six equal groups. The groups included control, ginger (100 mg/kg body weight), Maca (100 mg/kg body weight), endurance training (ET), ET + ginger and ET + Maca. Tissue levels of testosterone were measured along with the expression of genes involved in steroidogenesis (P450Scc, P450c17, HSD17β3, and P450 aromatase) and genes involved in its regulation (LHR, FSHR, GR, and SGP-1). Spermatogenesis was assessed by counting the number of spermatogenic cells (spermatogonia and spermatocytes), Leydig and Sertoli cells, and characteristics of the seminiferous tubules. Testicular levels of GPx, MDA, and TAC were evaluated. The gene expression of P450Scc and P450c17 were upregulated in the ginger (P = 0.03) (P = 0.03), endurance training (P = 0.02) (P = 0.003) and endurance training + ginger (P = 0.01) (P = 0.001) groups compared to the control group, respectively. The testicular expression of P450 aromatase gene increased in the endurance training (P = 0.007) and the endurance training + ginger (P = 0.049) groups compared to the control group. The results of P450Scc gene expression was upregulated in the endurance training (P = 0.001) and endurance training + Maca (P = 0.01) groups compared to the control group. Also, the expression of P450c17 was increased in the endurance training (P = 0.0005) and endurance training + Maca (P = 0.0014) groups compared to the control group. No significant difference was observed in the testicular expression of genes involved in the regulation of spermatogenesis (LHR, FSHR, and SGP-1) among all groups. The results indicated that the GR gene was up-regulated in the endurance training + ginger group compared to the ginger (P = 0.03) and endurance training group (P = 0.04). The level of TAC as oxidative parameter was increased in the endurance training + Maca group compared to the control (P = 0.0182), the Maca (P = 0.0008), and the endurance training (P = 0.02) groups. The level of MDA was decreased in endurance training + ginger group compared to the ginger (P = 0.01) and endurance training (P = 0.01) groups. The GPx activity indicated a protective effect and improved oxidative status in testicular tissue in the Maca, the ginger and the endurance training groups. Consistent with our steroidogenesis results, spermatogenesis parameters were significantly increased by Maca, ginger, endurance training, and their combination with endurance training compared to the control group (P < 0.05). It can be concluded that consuming ginger or Maca along with endurance training can strengthen the antioxidant system in testicular tissue and enhance steroidogenesis and spermatogenesis.
Role of bile acids in the pathogenesis and metabolic abnormalities of polycystic ovary syndrome (PCOS).
Wang Y, Shao X, Yang X
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41360233 · Publisher ↗
Bile acid, an important molecule regulating the endocrine system and metabolism, affects glucose, lipid, and energy homeostasis in the body and has emerged as a therapeutic target for diabetes and metabolic syndrome. Pol...
Bile acid, an important molecule regulating the endocrine system and metabolism, affects glucose, lipid, and energy homeostasis in the body and has emerged as a therapeutic target for diabetes and metabolic syndrome. Polycystic ovary syndrome (PCOS) is a reproductive endocrine-metabolic disorder that is accompanied by not only obesity and insulin resistance but also bile acid metabolism disorders. In this review, we summarize the role of bile acid metabolism in three typical phenotypes of PCOS, including abnormal glucose and lipid metabolism, abnormal follicular development, and hyperandrogenism, and explore the underlying pathophysiological mechanisms. The findings provide a novel perspective for further research on PCOS and potential targets for its diagnosis and treatment.
Tryptophan-steroid interactions in the brain-gut-microbiome axis: Neuroactive metabolites as biomarkers and therapeutic targets.
Ravishankar S, Ekambaram B, Boopathi N … +2 more , Rajagopal Sakthivel S, M C
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41354394 · Publisher ↗
Tryptophan metabolism plays a central role in connecting the brain, gut, and microbiome. Microbial and host-derived metabolites influence intestinal integrity, immune activity, and neural signaling, while steroid and neu...
Tryptophan metabolism plays a central role in connecting the brain, gut, and microbiome. Microbial and host-derived metabolites influence intestinal integrity, immune activity, and neural signaling, while steroid and neurosteroid hormones shape these pathways through receptor-mediated effects. Disturbance of this metabolic network contributes to neuropsychiatric, metabolic, and inflammatory disorders. This review integrates evidence from preclinical and clinical studies to explain how tryptophan catabolism interacts with microbial activity and steroid regulation. Key neuroactive metabolites involved in these interactions are discussed, along with their potential value as biomarkers and therapeutic targets. Current limitations of animal models and the need for human-focused, multi-omics approaches are also highlighted. Together, these insights outline how coordinated tryptophan-steroid-microbiome signalling influences health and disease and identify opportunities for more precise diagnostic and therapeutic strategies.
Vitamin D co-administration mitigates testicular and sperm dysfunction in high fat diet- induced obese mouse model.
Tan NAS, Giribabu N, Salleh N
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41349872 · Publisher ↗
UNLABELLED: Obesity, which is mostly related to high fat diet (HFD) consumption, could impair male reproductive function. How vitamin D (VD) co-administration ameliorates male reproductive dysfunction during obesity deve...
UNLABELLED: Obesity, which is mostly related to high fat diet (HFD) consumption, could impair male reproductive function. How vitamin D (VD) co-administration ameliorates male reproductive dysfunction during obesity development is not fully understood. Therefore, this study aims to investigate the effect of VD co-administered with HFD on testicular and sperm functions in mice and to unravel the underlying mechanisms involved. METHODS: Adult male ICR mice were given HFD with VD (HFDVD+) or without VD (HFDVD-), orally for 12 consecutive weeks. Immediately following sacrifice, blood was withdrawn and testes and epididymal sperm were harvested. RESULTS: HFDVD+ mice exhibited higher serum testosterone, FSH, and LH levels, higher expression of testicular VD receptor (VDR), retinoic acid receptor (RXR α/β/γ) and VD metabolizing enzymes (CYP27B1), testicular steroidogenic proteins (StAR, CYP11A1, 3β-HSD, 17β-HSD, CYP17A1, SF-1 except testicular aromatase), testicular spermatogenic proteins (PLZF, SOX9, SIRT1, AR, SMAD5, ER-α) and blood-testis barrier proteins (occludin, ZO-2, vimentin, connexin-43, N-cadherin) when compared to HFDVD- mice. Additionally, upregulation of testicular RANK and RANKL proteins and downregulation of testicular OPG protein were ameliorated in HFDVD+ mice. Epididymal sperm analysis revealed improvement in sperm parameters in HFDVD+ mice which positively correlated with serum VD levels. In HFDVD+ mice sperm, lesser downregulation of VDR, mitochondrial proteins (TOMM20, ATPB, COX IV), junctional adhesion molecule-A (JAM-A), and glucose transporter 1 (GLUT1) expression were observed. CONCLUSION: Co-administration of VD with HFD helps to ameliorate testicular and sperm dysfunctions during obesity development, suggesting VD role in overcoming male reproductive impairment in obesity.
Vitamin D metabolite ratio as a marker of nutritional bone health in adolescents.
Al-Daghri NM, Alenad AM, Sabico S … +8 more , Wani K, Al-Saleh Y, Khattak MNK, Alnaami AM, Fakhurji LT, Alokail MS, Reginster JY, Cavalier E
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41349871 · Publisher ↗
Vitamin D deficiency is a widespread public health issue among Saudi adolescents, posing significant risks to bone health and long-term well-being. Traditional markers such as serum 25-hydroxyvitamin D [25(OH)D] may not...
Vitamin D deficiency is a widespread public health issue among Saudi adolescents, posing significant risks to bone health and long-term well-being. Traditional markers such as serum 25-hydroxyvitamin D [25(OH)D] may not fully capture functional vitamin D status, particularly during critical growth periods such as adolescence. This study aimed to evaluate vitamin D metabolite levels and their association with calcium intake and bone health markers in Saudi adolescents, with a focus on the vitamin D metabolite ratio (VMR) as a potential indicator of functional vitamin D sufficiency. A cross-sectional analysis was conducted involving 949 (54 % females) Saudi adolescents. Serum levels of vitamin D metabolites, including 25(OH)D; 24,25-dihydroxyvitamin D [24,25(OH)₂D], and 25(OH)D₂, were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). VMR was calculated as the ratio of 24,25(OH)₂D to 25(OH)D. Dietary calcium intake was assessed via validated questionnaires. Parathyroid hormone (PTH) and serum calcium levels were analyzed in a subset of participants. Vitamin D deficiency was highly prevalent, with 86.5 % of participants showing insufficient 25(OH)D levels. Over 93 % had low 24,25(OH)₂D, 99.7 % had undetectable 25(OH)D₂, and 74.9 % exhibited low VMR. VMR was significantly associated with serum and dietary calcium intake among girls, but not boys, suggesting potential sex-specific metabolic differences. Additionally, only VMR showed a significant association with serum calcium. An inverse association between PTH and both total vitamin D (r = -0.28, p < 0.05) and serum calcium (r = -0.34, p < 0.01) was observed in the subset analysis. In conclusion, VMR may serve as a useful sex-specific biomarker of functional vitamin D status in adolescents. The findings highlight the importance of addressing both intake and metabolic processing of vitamin D to optimize bone health during adolescence.
Alterations of vitamin D metabolism and requirements in clinical conditions with impaired gastro-intestinal and renal function and in critical illness.
Schoenmakers I, Forbes A, Jones KS
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41344558 · Publisher ↗
Many studies show inverse relationships between the prevalence and severity of clinical conditions and vitamin D status. This may be partly due to reverse causality because of altered organ function, influencing vitamin...
Many studies show inverse relationships between the prevalence and severity of clinical conditions and vitamin D status. This may be partly due to reverse causality because of altered organ function, influencing vitamin D metabolism and bioavailability. Here we provide a narrative review of the impact of clinical conditions on vitamin D metabolism reviewing intestinal absorption, vitamin D binding protein (DBP) function and renal metabolism. Dietary vitamin D absorption is dependent on its incorporation in fat droplets in chylomicrons. Gastrointestinal inflammation and impaired fat digestion and absorption lead to decreased vitamin D bioavailability, whereas the hydroxylated form, 25-hydroxyvitamin D (25(OH)D), is less dependent on these factors. Vitamin D metabolites circulate predominantly bound to DBP which facilitates transportation, cellular uptake and regulates hydroxylation into 1,25-dihydroxy vitamin D (1,25(OH)D) and catabolic products. DBP also plays a key role in scavenging of actin upon cellular damage and inflammation and activation of the innate immune response. A decline in DBP due to actin-scavenging leads to alterations in vitamin D binding, bioavailability and metabolism. The kidney has several roles in vitamin D metabolism: internalisation and hydroxylation of 25(OH)D into 1,25(OH)D and catabolites and reabsorption of DBP-vitamin D metabolite complex from the glomerular filtrate. Renal damage leads to impairment of these functions. Specific guidance on vitamin D requirements accounting for alterations in vitamin D physiology with many clinical conditions is lacking, except for chronic kidney disease. Understanding how clinical conditions alter organ function and vitamin D metabolism is essential for management of vitamin D status and function.
Metformin improves polycystic ovary syndrome through the regulation of granulosa cell proliferation and apoptosis via the miR-103a-3p/PTEN signaling pathway.
Di Cheng, Chen Y, Tan Y … +5 more , Zhong Q, Liu H, Li L, Xie Y, Mo Z
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41325891 · Publisher ↗
Polycystic ovary syndrome (PCOS) is a common endocrine disorder, often characterized by polycystic ovarian, hyperandrogenism, and menstrual irregularities, which can lead to infertility and other metabolic issues. The me...
Polycystic ovary syndrome (PCOS) is a common endocrine disorder, often characterized by polycystic ovarian, hyperandrogenism, and menstrual irregularities, which can lead to infertility and other metabolic issues. The mechanisms underlying these symptoms remain complex, with granulosa cells proliferation and apoptosis playing a key role in the pathogenesis of PCOS. In this study, we investigate the potential of metformin to regulate the miR-103a-3p/PTEN signaling pathway in granulosa cells, which may help address these dysfunctions. We first created an in vitro PCOS model using KGN cells treated with testosterone propionate (TP) and tested the effects of metformin alongside miR-103a-3p mimics, inhibitors, and PTEN overexpression. Additionally, a PCOS rat model was developed through TP injections, and rats were treated with metformin at varying doses. Cell viability, proliferation, and apoptosis were assessed using MTT, EdU, and TUNEL staining techniques. The results showed that TP treatment reduced KGN cell viability and promoted apoptosis, while metformin treatment restored cell viability and improved these markers. Altering miR-103a-3p levels or PTEN expression further modulated cell proliferation and apoptosis, supporting the involvement of the miR-103a-3p/PTEN axis in PCOS pathophysiology. In the rat model, metformin alleviated metabolic and reproductive dysfunctions by regulating key biomarkers. These findings suggest that metformin can promote granulosa cells proliferation and inhibit apoptosis, providing a promising therapeutic approach for PCOS through the miR-103a-3p/PTEN axis.
Research progress on the prevention and treatment of diseases with traditional Chinese medicine: A focus on BA receptors.
Guo X, Zhang M, Xie M
J Steroid Biochem Mol Biol · 2026 Feb · PMID 41308927 · Publisher ↗
Bile acids (BAs) are crucial endogenous components involved in metabolic processes, and can also function as signaling molecules by specific BA receptors. Common BA receptors, such as the Farnesoid X Receptor (FXR), Take...
Bile acids (BAs) are crucial endogenous components involved in metabolic processes, and can also function as signaling molecules by specific BA receptors. Common BA receptors, such as the Farnesoid X Receptor (FXR), Takeda G protein-coupled receptor 5 (TGR5), Pregnane X receptor (PXR), and Vitamin D receptor (VDR), play crucial roles in regulating BA metabolism, lipid metabolism and glucose metabolism. Dysregulation of BA metabolism often interferes with the functions of these receptors and contributes to the pathogenesis of various diseases, including liver diseases, diabetes, hyperlipidemia, hypercholesterolemia, and gallstones. Traditional Chinese Medicine (TCM) has certain advantages in preventing and treating these diseases. This review summarizes current research on the mechanisms by which TCM interventions, including single herbs, extracts, and compounds, act on BA receptors. Using these receptors as a starting point, we elucidate how TCM influences various metabolic-related diseases through BA receptor-mediated and other pathways. The findings summarized herein provide valuable insights for future research on the prevention and treatment of metabolic diseases.
Evaluation of endogenous steroid sulfates and glucuronides in urine after oral and transdermal administration of testosterone. Part II: Female participants.
Pfeffer S, Gmeiner G, Dikic N … +2 more , Andjelkovic M, Forsdahl G
J Steroid Biochem Mol Biol · 2026 Feb · PMID 41271119 · Publisher ↗
Detecting testosterone (T) doping remains a significant challenge, driving the search for novel biomarkers and advancements in the steroidal Athlete's Biological Passport (ABP). Phase II metabolites of endogenous anaboli...
Detecting testosterone (T) doping remains a significant challenge, driving the search for novel biomarkers and advancements in the steroidal Athlete's Biological Passport (ABP). Phase II metabolites of endogenous anabolic androgenic steroids (EAAS) have emerged as promising biomarkers, demonstrating prolonged detection times (DTs) and greater sensitivity compared to conventional biomarkers. Studies involving male participants investigated the effect of intramuscular, oral, and transdermal administration of T on these biomarkers and proposed their integration in future urinary steroid profiling. However, before the inclusion of phase II EAAS metabolites, it is crucial to address a range of possible doping scenarios and the influence of known confounding factors, like ethnicity or sex, on the steroid profile. This study addresses this gap by investigating the impact of oral and transdermal T administration on phase II EAAS metabolites in both men and women. This second part of the study presents the results for female participants, which have not been included in prior research on this topic. Results partially confirm the trends observed in men, with sulfate ratios exhibiting prolonged detection times and higher sensitivity compared to conventional steroid profile biomarkers following multiple oral and transdermal T administration. However, the evaluation in women showed greater variability due to lower steroid concentrations and greater fluctuations influenced by the menstrual cycle. This study provides additional evidence supporting the inclusion of phase II EAAS metabolites for enhanced detection of T doping. Further, it underscores the need for further research to address the unique challenges of female steroid profiling.
Corrigendum to "G protein-coupled estrogen receptor reduces the breast cancer cell survival by regulating the IRE1α/miR-17-5p/TXNIP pathway" [J. Steroid Biochem. Mol. Biol. 252 (2025) 106770].
Mohammad-Sadeghipour M, Nematollahi MH, Sahebazzamani M … +4 more , Ahmadinia H, Hajizadeh MR, Mahmoodi M, Sahebkar A
J Steroid Biochem Mol Biol · 2026 Feb · PMID 41253616 · Publisher ↗
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Metabolic and signaling interplay in the adipocyte-tumor microenvironment.
Sivalingam AM
J Steroid Biochem Mol Biol · 2026 Feb · PMID 41253263 · Publisher ↗
Adipocytes are now recognized as active regulators of cancer progression and therapy resistance. Through metabolic, immune, and signaling interactions, they promote tumor cell proliferation, stemness, and survival. This...
Adipocytes are now recognized as active regulators of cancer progression and therapy resistance. Through metabolic, immune, and signaling interactions, they promote tumor cell proliferation, stemness, and survival. This review examines adipocyte tumor crosstalk in triple-negative breast cancer (TNBC) and oral squamous cell carcinoma (OSCC), focusing on how adipocyte-derived mediators influence tumor aggressiveness and treatment outcomes. Important adipocyte-secreted factors including complement C3, CXCL12, leptin, and adiponectin drive oncogenic signaling pathways that support tumor growth. In OSCC, C3/C3aR activation enhances cancer stemness, while in TNBC, bisphenol A-induced CXCL12 activates the CXCL12/CXCR4-PI3K/AKT axis, promoting epithelial-mesenchymal transition and therapy resistance. Additionally, circular RNAs and metabolic enzymes such as GCLC regulate HIF-1α, NF-κB, β-catenin, and mTOR pathways, further sustaining tumor progression. By establishing a tumor-supportive niche, adipocytes contribute significantly to therapy resistance. Targeting these adipocyte-tumor interactions represents a promising approach to inhibit oncogenic signaling and restore treatment sensitivity. Disrupting this metabolic crosstalk may reprogram the tumor microenvironment, offering new combinatorial strategies for aggressive cancers like TNBC and OSCC.
Molecular dynamics and electronic structure insights into chloroquine, quercetin, and luteolin binding to HPV-16 E2 protein.
Osailan R, Habeeb T, Khalafalla MAH … +1 more , Bashal AH
J Steroid Biochem Mol Biol · 2026 Feb · PMID 41248835 · Publisher ↗
Human papillomavirus type 16 (HPV-16) E2 protein has key roles in the control of viral DNA replication. Small, biocompatible ligands with known antiviral activity and acceptable toxicity that bind to E2 and slightly chan...
Human papillomavirus type 16 (HPV-16) E2 protein has key roles in the control of viral DNA replication. Small, biocompatible ligands with known antiviral activity and acceptable toxicity that bind to E2 and slightly change its motion may disturb these functions. In this study, we used 100 ns molecular dynamics simulations together with electronic-structure calculations to investigate how chloroquine, quercetin, and luteolin interact with E2. Analysis of protein motion (RMSD, Rg, and RMSF) showed that the protein remained stable, but ligand binding was linked to changes in the flexibility of residues near DNA-binding and other functional regions. All three ligands remained mainly near these regions during the simulations. Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) analysis supported stable binding, with quercetin showing the strongest estimated affinity. The HOMO-LUMO values and global reactivity descriptors were similar for the ligands, which may help explain their ability to settle in similar regions of E2. These findings suggest that the three ligands can influence functional areas of E2 and may indicate possible synergistic effects against protein-driven viral activity.
Context-dependent effects of progesterone 4-pregnene metabolites on apoptosis and proliferation in ovarian cancer cell lines IGROV-1 and SK-OV-3.
Sanhueza MA, Pelegrina LT, Cáceres ARR … +6 more , Cardone DA, Roig Cerdeño M, Ibañez Cannavó J, Bruna FA, Cuello-Carrión FD, Laconi MR
J Steroid Biochem Mol Biol · 2026 Feb · PMID 41248834 · Publisher ↗
Ovarian cancer remains the deadliest gynecological malignancy, with limited therapeutic options and high recurrence rates. Although progesterone (P4) metabolism has been implicated in hormone-related cancers, the biologi...
Ovarian cancer remains the deadliest gynecological malignancy, with limited therapeutic options and high recurrence rates. Although progesterone (P4) metabolism has been implicated in hormone-related cancers, the biological roles of its 4-pregnene metabolites, 3α-dihydroprogesterone (3αHP) and 20α-dihydroprogesterone (20αHP), in ovarian cancer have not been explored. In this study, we investigated the effects of 3αHP and 20αHP on proliferation, apoptosis, migration, and clonogenic potential in two human ovarian cancer cell lines (IGROV-1 and SK-OV-3). Both metabolites significantly inhibited cell proliferation and clonogenicity. In IGROV-1 cells, 20αHP increased cleaved caspase-3 expression, and in SK-OV-3 increased early apoptosis, indicating pro-apoptotic activity. Neither compound altered cell migration in either cell line. These findings provide the initial evidence that 4-pregnene metabolites of progesterone modulate key features of ovarian cancer cell behavior, offering potential insights into alternative hormone-based therapeutic strategies.
Urinary metabolomic biomarkers for diagnosing central precocious puberty and revealing sexual dimorphism.
Wen L, Wu S, Wu J … +4 more , Li Z, Chen J, Shen G, Feng J
J Steroid Biochem Mol Biol · 2026 Feb · PMID 41248833 · Publisher ↗
BACKGROUND: The incidence of central precocious puberty (CPP) is rising, especially during the COVID-19 pandemic. Early detection is crucial to prevent adverse outcomes in affected children. Current diagnostic methods ar...
BACKGROUND: The incidence of central precocious puberty (CPP) is rising, especially during the COVID-19 pandemic. Early detection is crucial to prevent adverse outcomes in affected children. Current diagnostic methods are invasive and inconsistent, necessitating less invasive approach. Metabolomics offers a novel method to reveal CPP mechanisms and identify biomarkers. OBJECTIVES: This study aims to identify and validate urinary metabolomic biomarkers for the diagnosis of CPP and to elucidate the sex-dimorphic metabolic mechanisms underlying this condition, with the ultimate goal of developing non-invasive diagnostic approaches. METHODS: Urine samples from CPP patients and aged-matched controls were analyzed using NMR-based metabolomics. Statistical analyses identified potential CPP biomarkers. LASSO regression and binary logistic regression (LR) screened diagnostic groups, validated using random forest, LR and support vector machine to generate receiver operating characteristic (ROC) curves and calculate area under curves (AUCs). Direct comparison between CPP boys and girls discerned gender-specific metabolic characteristics. RESULTS: The study identified 13, 13, 17 and 12 potential markers for CPP girls versus prepubertal/adolescent girls, and CPP boys versus prepubertal/adolescent boys, respectively. Diagnostic groups with 7, 3, 3 and 3 biomarkers were selected, yielding mean AUCs of 0.928, 0.942, 0.984 and 0.865. Eight gender-specific markers were identified. CONCLUSIONS: The study reveals distinct metabolic differences between CPP children and controls, with gender variations. Obesity is a risk factors for CPP in girls, while CPP boys exhibit faster amino acid turnover and bone growth. Gender comparison shows distinct metabolic profiles, confirming sexual dimorphism in CPP presentation. These findings suggest that metabolic regulation interventions may be beneficial in managing CPP and highlight the need for gender-specific diagnostic approaches.
Nandrolone decanoate induces liver damage via TGF-β/Smad3/miR-29 and regulation of FAT/CD36, PTP1B, HNF4A expression in male rats: Rescue effect of N-acetylcysteine.
Mohammadpour-Asl S, Shirpoor A, Alipour S … +1 more , Naderi R
J Steroid Biochem Mol Biol · 2026 Feb · PMID 41242401 · Publisher ↗
Anabolic-androgenic steroid (AAS) abuse is associated with damage to various organs, including the liver. However, the underlying molecular mechanisms remain unclear. This study was conducted to elucidate the effect of n...
Anabolic-androgenic steroid (AAS) abuse is associated with damage to various organs, including the liver. However, the underlying molecular mechanisms remain unclear. This study was conducted to elucidate the effect of nandrolone decanoate on liver injury, both alone and in combination with N-acetylcysteine (NAC), and its related mechanisms. Twenty-four male Wistar rats were randomly subdivided into three groups: Control (Con), Nandrolone (10 mg/kg) (ND), and Nandrolone + NAC (ND+NAC: 150 mg/kg daily). After 6 weeks, nandrolone treatment led to increased levels of triglycerides, cholesterol, LDL, AST, ALT, and ALP, along with a decreased HDL level compared to the control group. ND administration also elevated the expression of PTP1B, HNF4A, and FAT/CD36 genes, as well as protein levels of MMP-2, MMP-9, TGF-β1, SMAD-3, and SREBP-1. miRNA-29b levels decreased in liver tissue following nandrolone exposure, as determined by RT-PCR. Moreover, histopathological examination showed increased fibrosis after ND treatment. Consumption of NAC along with ND partially ameliorated gene and protein expression alterations and fibrotic changes, and improved the undesirable lipid profile and liver enzyme levels compared to the ND group. These findings indicate that ND-induced liver abnormalities may be partly associated with lipid homeostasis changes mediated by overexpression of the aforementioned genes and proteins. They also demonstrate that these effects can be reduced by using NAC as an antioxidant and anti-inflammatory agent.
Vitamin D is glucoprotective in aging males but not females.
Ginnard OZB, Morales M, Youn JY … +2 more , Xu Y, Sisley SR
J Steroid Biochem Mol Biol · 2026 Feb · PMID 41242400 · Full text
Vitamin D supplementation is linked to many beneficial health outcomes in the geriatric population, such as decreased mortality, epigenetic aging, and fracture risk. Conversely, type 2 diabetes is strongly linked to vita...
Vitamin D supplementation is linked to many beneficial health outcomes in the geriatric population, such as decreased mortality, epigenetic aging, and fracture risk. Conversely, type 2 diabetes is strongly linked to vitamin D deficiency in older adults. However, there is a discrepancy between clinical trials in adults on the efficacy of vitamin D treatment in prediabetes and diabetes. In addition, human data indicates there may be sexual dimorphism in the effect of vitamin D deficiency on dysglycemia that is more pronounced in men. These incongruities may be due to our limited understanding of the underlying mechanisms of vitamin D in glucose homeostasis among its vast target tissues across the body. Here we describe the physiological effects of vitamin D supplementation in an aged, non-obese mouse model on glucose homeostasis and associated tissue-specific gene regulation. Specifically, we found that 1) increased dietary vitamin D intake can improve glucose regulation in lean, aged male mice, and 2) these male mice also had decreased Glut4 and Insr expression in a diet low in vitamin D in various tissues indicating that dietary vitamin D may be a sex-specific key mediator in regulating glucose tolerance and protecting against insulin resistance.
Effect of race, gender and age on intrinsic diurnal variation of serum calcifediol: Insights into vitamin D toxicity.
Bishop CW, Choe J, Strugnell SA … +2 more , Tabash S, Ashfaq A
J Steroid Biochem Mol Biol · 2026 Feb · PMID 41238065 · Publisher ↗
Intrinsic diurnal variation of serum calcifediol (25-hydroxyvitamin D) was evaluated in healthy United States (US) adults by race, gender and age. Eligible participants (18-55 years old, body mass index 18-30 kg/m, body...
Intrinsic diurnal variation of serum calcifediol (25-hydroxyvitamin D) was evaluated in healthy United States (US) adults by race, gender and age. Eligible participants (18-55 years old, body mass index 18-30 kg/m, body weight ≥ 50 kg) were enrolled with gender balance into two groups by race: first generation Japanese (n = 35) and non-Japanese (n = 32). "First generation Japanese" was defined as having Japanese parents and grandparents and residing outside Japan for < 5 years without major lifestyle or dietary changes. "Non-Japanese" were of non-Asian descent and included 14 African-Americans, 16 Caucasians and 2 of "Other" race. Vitamin D supplementation during the prior 28 days was an exclusion criterion. Participants were housed for two days in a phase 1 unit shielded from sunlight and fed timed standardized meals devoid of vitamin D. Serum calcifediol, measured by LC-MS/MS on Day 2 at 0, 2, 4, 6, 8, 10, 12, 14, 16, 20 and 24 h, had a minor circadian rhythm (p = 0.0081) having a midline statistic of rhythm (MESOR) of 21.5 ng/mL, an amplitude of 0.19 ng/mL and an acrophase at 5:24 a.m. Mean inter-participant variation was high (CV of 30.89 %) while intra-participant variation was low (5.54 %), only nominally exceeding the assay precision (4.10 %). No significant differences in rhythmicity were observed between subgroups based on race, gender or age. These data show that intrinsic diurnal variation of circulating calcifediol is low, suggesting that avoidance of abrupt iatrogenic changes in serum total 25-hydroxyvitamin D concentrations may be important for minimizing the risk of toxicity.
Excess aldosterone and cortisol promote myocardial iron deficiency: A potential pathway to cardiac injury.
Cirovic A
J Steroid Biochem Mol Biol · 2026 Jan · PMID 41235980 · Publisher ↗
Mineralocorticoid receptor antagonists (MRAs) such as finerenone have shown clinical benefits in heart failure, yet their full mechanisms remain unclear. Recent evidence suggests a novel role of aldosterone in disrupting...
Mineralocorticoid receptor antagonists (MRAs) such as finerenone have shown clinical benefits in heart failure, yet their full mechanisms remain unclear. Recent evidence suggests a novel role of aldosterone in disrupting myocardial iron homeostasis. Aldosterone, via mineralocorticoid receptor (MR) activation, downregulates key iron transporters like transferrin receptor 1 (TfR1) through SGK1 signaling, contributing to myocardial iron deficiency (MID). Cortisol, which circulates at much higher levels than aldosterone and shares similar MR affinity, may similarly promote MID-especially in tissues like the heart where 11β-HSD2 activity is low. Iron deficiency in cardiomyocytes impairs mitochondrial function, reduces ATP synthesis, and promotes fibrosis and inflammation. MRAs may counteract these effects by restoring iron uptake and improving myocardial energetics. This emerging aldosterone-iron axis offers novel insight into the cardiac effects of MR activation and identifies iron homeostasis as a potential therapeutic target. Further research is warranted to explore MRA-mediated modulation of myocardial iron metabolism.
Calcitriol's role in fetal bone and mineral metabolism: Evidence from human and animal studies.
Kovacs CS
J Steroid Biochem Mol Biol · 2026 Feb · PMID 41223950 · Publisher ↗
Fetal mineral and bone metabolism is regulated differently compared to the neonate, child, or adult. A fundamental design difference is that the fetal mineral supply comes from active transport across the placenta rather...
Fetal mineral and bone metabolism is regulated differently compared to the neonate, child, or adult. A fundamental design difference is that the fetal mineral supply comes from active transport across the placenta rather than the intestines. Calcium, phosphorus, and magnesium also circulate at higher concentrations in the fetal blood as compared to maternal or normal adult values, which facilitates rapid accretion of skeletal mineral content before birth. Given the dependence of postnatal mineral and bone homeostasis on calcitriol, it may be expected that calcitriol and the vitamin D receptor (VDR) would be critically required during fetal development. However, calcitriol circulates at low levels in the fetal circulation, kept suppressed by increased 24-hydroxylated catabolism and low parathyroid hormone (PTH). Calcitriol does not regulate placental mineral transport, while the intestines are a trivial route of mineral delivery in the fetus. Consequently, fetuses lacking vitamin D, calcitriol, or VDRs are born with normal serum mineral concentrations, PTH, and skeletal development/mineralization. After birth, serum calcium falls and phosphorus rises, and these events trigger an increase in PTH and a subsequent rise in calcitriol. The intestines become the main source of mineral supply and it is then that the neonatal may begin to suffer the consequences of disrupted vitamin D physiology. This review discusses key data arising from animal and human studies (clinical trials, case series, epidemiological studies, associational analyses) in order to address our current knowledge on the role of vitamin D, calcitriol, and VDR in regulating fetal mineral and bone homeostasis.
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