The Journal Of Steroid Biochemistry And Molecular Biology[JOURNAL]
Sun
200 papers
Acetoacetyl-CoA synthetase modulates lipid partitioning and cholesterol-related gene expression in NEFA-challenged neonatal bovine hepatocytes.
Tian Y, Wang S, Loor JJ … +8 more , Fan W, Chang Y, Yang T, Zhang B, Xia C, Xu C, Li X, Yang W
J Steroid Biochem Mol Biol · 2026 Sep · PMID 42119830 · Publisher ↗
Ketosis is a common metabolic disorder in dairy cows, typically occurring during early postpartum negative energy balance and characterized by hyperketonemia, hepatic lipid accumulation, and oxidative stress. Although ac...
Ketosis is a common metabolic disorder in dairy cows, typically occurring during early postpartum negative energy balance and characterized by hyperketonemia, hepatic lipid accumulation, and oxidative stress. Although acetoacetyl-CoA synthetase (AACS) plays a key role in ketone body metabolism, its association with acetoacetate (AcAc) utilization during ketosis remains unclear. This study aimed to assess the effects of AACS on fatty acid and cholesterol metabolic pathways in neonatal bovine hepatocytes exposed to high concentrations of non-esterified fatty acids (NEFA). Liver tissues were collected from healthy (n = 6; BHBA < 1.0 mM) and ketotic (n = 6; BHBA > 3.0 mM) dairy cows. Additionally, hepatocytes isolated from neonatal calves were treated with 1.2 mM NEFA to establish an in vitro ketotic model. To evaluate the role of AACS, two separate experimental approaches were employed using NEFA-challenged hepatocytes: siRNA-mediated AACS knockdown and exogenous AcAc supplementation. Results demonstrated that liver tissues from ketotic cows and NEFA-treated cells exhibited upregulation of AACS and HMGCS2, along with key lipogenic proteins (SREBF1, ACACA, and FASN). In contrast, the expression of cholesterol synthesis and efflux factors (SREBF2, HMGCR, ABCA1, ABCG5, and ACAT2) was downregulated. NEFA challenge also reduced BDH1 and CPT1A levels, decreased intracellular total cholesterol, increased TAG accumulation, and induced oxidative stress and mitochondrial dysfunction. Silencing AACS partially attenuated NEFA-induced lipid accumulation but further suppressed cholesterol synthesis and efflux-related gene expression. Conversely, AcAc supplementation upregulated the expression of cholesterol synthesis and efflux-related genes but exacerbated lipid deposition, oxidative stress, and mitochondrial dysfunction. Overall, these findings indicate that NEFA-induced upregulation of AACS abundance in hepatocytes may modulate the partitioning of acetoacetate toward de novo lipogenesis and alter cholesterol synthesis and efflux-related gene expression.
Progesterone and estrogen signaling in uterine fibroids: A tale of two interconnected pathways.
Saini K, Singh S, Garg N
J Steroid Biochem Mol Biol · 2026 Sep · PMID 42102980 · Publisher ↗
Uterine fibroids are monoclonal tumors occurring in females of reproductive age. The etiology of UFs is still not completely known, but they arise from a single mutation in smooth muscle cells of the uterus. These are ho...
Uterine fibroids are monoclonal tumors occurring in females of reproductive age. The etiology of UFs is still not completely known, but they arise from a single mutation in smooth muscle cells of the uterus. These are hormone-dependent tumors, as they usually shrink after menopause. Surgical treatment options like hysterectomy and myomectomy are considered definitive treatment for UFs, but they are very costly and not acceptable for all females. Various herbal and synthetic drugs are used for the management of UFs, but none of them can completely resolve fibroids. They only reduce the symptoms associated with UF; also, the associated side effects make them unfit for use. Currently, natural compounds along with acupuncture have been investigated as therapies for UF; however, their clinical studies are limited. Therefore, there is a need for a drug that could target various signaling pathways in UF. For that, there is a need to understand the complete pathology of UF. This review focuses on the estrogen and progesterone signaling pathways associated with UFs. This will help in understanding the pathology of UFs. By targeting multiple signaling pathways, we can potentially refine and improve the management strategies for uterine fibroids.
Dehydroepiandrosterone alleviates pulmonary fibrosis by modulating the TLR4/NF-κB/NLRP3 signaling cascade in macrophages.
Xie Q, Zhao X, Lu Y … +1 more , Shuai S
J Steroid Biochem Mol Biol · 2026 Sep · PMID 42055198 · Publisher ↗
Idiopathic pulmonary fibrosis (IPF) is a severe progressive lung disease with limited treatment options. Dehydroepiandrosterone (DHEA), an endogenous steroid hormone, possesses anti-inflammatory and anti-fibrotic propert...
Idiopathic pulmonary fibrosis (IPF) is a severe progressive lung disease with limited treatment options. Dehydroepiandrosterone (DHEA), an endogenous steroid hormone, possesses anti-inflammatory and anti-fibrotic properties, but its mechanism of action in pulmonary fibrosis (PF) remains incompletely understood. This study aimed to investigate whether DHEA alleviates PF by modulating macrophage-driven inflammatory responses. An in vitro model of PF was established using conditioned medium from LPS-stimulated, PMA-differentiated THP-1 macrophages to treat MRC-5 pulmonary fibroblasts. DHEA pretreatment (5-20 μM) was applied to macrophages, and the TLR4-specific inhibitor TAK-242 was used for mechanistic validation. Inflammatory cytokines were measured by ELISA, protein expression of TLR4/NF-κB/NLRP3 cascade components and extracellular matrix markers (α-SMA, Collagen I) by Western blotting, and cell proliferation by CCK-8 and flow cytometry. DHEA significantly reduced LPS-induced secretion of TNF-α, IL-6, IL-1β, and IL-18 from macrophages. It downregulated TLR4 expression, inhibited NF-κB phosphorylation, and suppressed NLRP3 inflammasome activation (NLRP3, ASC, Caspase-1). Furthermore, DHEA treatment of macrophages prevented their conditioned medium from inducing abnormal proliferation of MRC-5 cells and reduced α-SMA and Collagen I expression in these fibroblasts, similar to the effects of TAK-242. In conclusion, DHEA alleviates inflammatory responses and in vitro pulmonary fibrosis by blocking the TLR4/NF-κB/NLRP3 signaling cascade in macrophages, providing a new mechanistic basis for its potential therapeutic application in PF.
Detection of activin A and follistatin as potential biomarkers in women with ovarian endometriosis.
Makki NF, Kadhum SH
J Steroid Biochem Mol Biol · 2026 Jul · PMID 42035808 · Publisher ↗
Endometriosis is a condition characterized by the growth of tissue similar to the uterine lining outside the uterus. This study aimed to evaluate certain sex hormones and determine the levels of activin A and follistatin...
Endometriosis is a condition characterized by the growth of tissue similar to the uterine lining outside the uterus. This study aimed to evaluate certain sex hormones and determine the levels of activin A and follistatin in women with endometriosis. The study included 45 women with ovarian endometriosis and 45 healthy women as a control group. Hormone levels were measured using a VIDAS analyzer (bioMérieux, France), while activin A and follistatin levels were estimated using ELISA (BT LAB). The baseline characteristics (age, weight, BMI, WHR, WHtR, education, and residency) of the patients were comparable to those in controls (P > 0.05). Similarly, there was no difference in LH and prolactin levels (P > 0.05). Patients with endometriosis had significantly higher FSH (7.17 ± 1.76 vs. 5.99 ± 2.22, P = 0.010) and estradiol levels (136.67 ± 27.27 vs. 57.84 ± 15.16, P < 0.001), while progesterone (0.35 ± 0.11 vs. 0.44 ± 0.16, P = 0.045), testosterone [0.69 (0.45-0.82) vs. 0.81 (0.73-0.88), P = 0.001], and AMH [0.24 (0.15-0.36) vs. 4.08 (2.42-7.34), P = 0.001] were significantly lower. Activin A [11.24 (11.02-11.81) vs. 1.26 (1.02-2.11), P < 0.001] and follistatin [23.36 (19.53-46.86) vs. 12.40 (8.81-18.93), P < 0.001] were markedly elevated in patients compared to controls. The results for Activin A and Follistatin also showed a significant increase, indicating their potential use as promising biomarkers in the diagnosis of endometriosis.
Novel 5α-reductase inhibitors unlinked to depression-like phenotypes in rat model of BPH.
Khanna B, Rana P, Saini A … +2 more , Sah SP, Dhingra N
J Steroid Biochem Mol Biol · 2026 Sep · PMID 42019639 · Publisher ↗
Finasteride clinically approved for the treatment of benign prostatic hyperplasia exerts its therapeutic effect by inhibiting type II 5α-reductase, thereby reducing dihydrotestosterone levels, leading to prostate shrinka...
Finasteride clinically approved for the treatment of benign prostatic hyperplasia exerts its therapeutic effect by inhibiting type II 5α-reductase, thereby reducing dihydrotestosterone levels, leading to prostate shrinkage and symptomatic relief. However, finasteride also influences the levels of neurosteroids (allopregnanolone) and has been linked to depression-like behavior and impaired neurogenesis. Preclinical and clinical studies have shown that finasteride can robustly induce depressive behavior and can inhibit hippocampal neurogenesis in mice attributed to altered neurosteroids levels. Hence discovery and development of 5α-reductase inhibitors that are effective and devoid of depressionlike effect is essential. The aim of the present study is to assess the safety profile of newly synthesised steroidal 5α-reductase inhibitors. Six compounds from two series were synthesized and screened. Based on in silico docking against human 5α-reductase type II and reduction of serum DHT levels, ND-1 and ND-5 were identified as lead candidates. Both showed strong binding affinities (ND-1: -10.2 kcal/mol; ND-5: -9.8 kcal/mol) comparable to finasteride (-10.5 kcal/mol) and significantly reduced serum DHT in vivo. ND-1 and ND-5 were further evaluated in a testosterone-induced BPH rat model and assessed for depression-like effects following chronic treatment using locomotor activity, sucrose splash, and forced swim tests, along with serum allopregnanolone estimation. In the BPH model, both compounds markedly decreased prostate weight, seminal vesicle weight, demonstrating efficacy comparable to finasteride. Importantly, unlike finasteride, they did not induce depression-like behaviour and preserved serum allopregnanolone levels, highlighting their potential as safer alternatives. However, further studies are required to understand the underlying molecular mechanisms.
Age-specific centiles for fibroblast growth factor 23 and its associations with mineral and bone metabolism in healthy children.
Piec I, Chu A, Nichols B … +9 more , Lewis C, Thoroughgood CW, Gerasimidis K, Schoenmakers I, Dunn R, Tang JC, Chipchase A, Fraser WD, Webb EA
J Steroid Biochem Mol Biol · 2026 Jul · PMID 41991079 · Publisher ↗
BACKGROUND: Fibroblast Growth Factor 23 (FGF23) regulates phosphate and vitamin D metabolism and is implicated in pediatric disorders such as X-linked hypophosphatemia and CKD-mineral and bone disorder. Accurate interpre...
BACKGROUND: Fibroblast Growth Factor 23 (FGF23) regulates phosphate and vitamin D metabolism and is implicated in pediatric disorders such as X-linked hypophosphatemia and CKD-mineral and bone disorder. Accurate interpretation in children requires age-adjusted centile charts. OBJECTIVE: To construct age- and sex-specific centile charts for intact (iFGF23) and C-terminal (cFGF23) FGF23 in healthy UK children and examine associations with mineral and bone metabolism markers. METHODS: In a cross-sectional cohort of 430 children aged 0-16 years, plasma iFGF23 and cFGF23 were measured using DiaSorin and Quidel immunoassays. Age-specific centiles (2.5th-97.5th) were generated using GAMLSS modeling. Serum phosphate, albumin-adjusted calcium (AdCa), vitamin D metabolites, PTH, and bone turnover markers (PINP, CTX, NTX, BAP) were assessed. Associations were evaluated using LN-transformed regression and Pearson correlations. RESULTS: FGF23 concentrations declined with age, with highest values in infancy. At 2 years, median iFGF23 was 43.0 pg/mL (2.5-97.5th centiles: 20.8-81.6 pg/mL), while by 16 years, the median remained 42.9 pg/mL (20.8-81.5 pg/mL). For C-terminal FGF23 (cFGF23), the median was 98.2 RU/mL (2.5-97.5th centiles: 47.0-225.4 RU/mL) at 2 years and 80.2 RU/mL (38.4-184.1 RU/mL) at 16 years (p < 0.001). Correlation analyses showed weak but statistically significant associations of cFGF23 with PINP (r = 0.199, p < 0.001) and NTX (r = 0.150, p = 0.005), while iFGF23 exhibited similar weak correlations, with PINP (r = 0.120, p < 0.016) and BAP (r = 0.121, p = 0.013). CONCLUSION: We constructed age-specific centile charts for iFGF23 and cFGF23 in healthy children required for the interpretation of FGF23 in clinical practice and to provide a foundation for improved management of pediatric disorders in phosphate and vitamin D metabolism. Phosphate was the strongest predictor of both iFGF23 and cFGF23. Age and 25OHD predicted iFGF23 but not cFGF23. Both were correlated with markers of bone metabolism.
Chronic mifepristone administration induces obese sarcopenia, hepatic steatosis and insulin resistance in androgen-deprived male mice.
Shang J, Yan K, Liu L … +9 more , Jin C, Ran L, Zhang J, Wu P, Meng F, Zeng X, Cao X, Li H, Han X
J Steroid Biochem Mol Biol · 2026 Jul · PMID 41985637 · Publisher ↗
Both glucocorticoids receptor (GR) and peroxisome proliferator-activated receptor-γ (PPARγ) are critical metabolic checkpoints in endocrine control of whole-body energy homeostasis. Mifepristone, which serves as a non-se...
Both glucocorticoids receptor (GR) and peroxisome proliferator-activated receptor-γ (PPARγ) are critical metabolic checkpoints in endocrine control of whole-body energy homeostasis. Mifepristone, which serves as a non-selective antagonist for GR, androgen receptor (AR) and progesterone receptor (PR), but an agonist for PPARγ, has been clinically approved for the treatment of Cushing's syndrome and as an anti-contraceptive agent. However, the side effects of its chronic administration on metabolism via GR and/or PPARγ are largely unknown. Adult male mice were underwent bilateral orchiectomy to remove metabolic interference derived from sex steroid hormones, and then intraperitoneally administered of mifepristone at a dose of 30 mg/kg every other day for consecutive 28 days. Biochemical, histological and RNA-seq analyses were performed on critical metabolic organs. Resultantly, compared to the vehicle-treated controls, chronic mifepristone administration induced obese sarcopenia, hepatic steatosis and insulin resistance, accelerated thymus aging, but prevented bone loss in male mice. Mechanically, transcriptomic profiling analysis indicates that chronic mifepristone administration drives obesity, hepatic steatosis and insulin resistance via activating PPARγ signaling, but induces sarcopenia and prevents bone loss by antagonizing GR signaling. Further in vitro cell culture studies confirmed that mifepristone addition promotes preadipocyte differentiation and hepatocellular lipid accumulation via stimulating PPARγ-dependent de novo lipogenesis. Collectively, these results reveal multifaceted tissue-specific metabolic disorders of chronic mifepristone exposure, providing critical implications for understanding the clinical risks of chronic mifepristone use.
The loss of Cldn12 and functional Trpv6 leads to compensatory upregulation of colonic Trpv5 and reduced bone mineral density.
Deluque AL, Pan W, O'Neill D … +4 more , Bogdanovic M, Dimke H, Doschak MR, Alexander RT
J Steroid Biochem Mol Biol · 2026 Jul · PMID 41966491 · Publisher ↗
Calcium (Ca²⁺) homeostasis is tightly regulated by the coordinated actions of the intestine, kidneys and bone. Ca²⁺ transport occurs via either a paracellular pathway, which depends on the expression of select claudins,...
Calcium (Ca²⁺) homeostasis is tightly regulated by the coordinated actions of the intestine, kidneys and bone. Ca²⁺ transport occurs via either a paracellular pathway, which depends on the expression of select claudins, including claudin-12 (CLDN12) in the tight junction, or a transcellular pathway, involving apical influx through TRPV6. While disruption of paracellular or transcellular pathways impairs transepithelial Ca²⁺ flux, Cldn12-deficient mice and Trpv6 mutant (Trpv6) mice do not display alterations in Ca²⁺ balance as reported previously, perhaps because one pathway compensates for the other. To test this hypothesis, we generated a double knockout mouse (DKO, Cldn12/ Trpv6) to assess Ca²⁺ homeostasis using metabolic cage balance studies, quantitative real-time PCR, and micro-computed tomography (Micro-CT). Despite lacking these key Ca²⁺ transport mechanisms, DKO mice maintained normal blood Ca²⁺. However, PTH and calcitriol were significantly elevated, as were renal Cyp27b1 and Cyp24a1 expression, consistent with hormonal compensation. The proximal colon and cecum exhibited significant compensatory changes in Ca²⁺-regulatory gene expression, including upregulation of the Ca²⁺ buffer S100g and basolateral extrusion mechanism Atp2b1. Notably, the Ca²⁺ channel Trpv5, which is absent from the intestine, became detectable in the proximal colon and cecum, but not in the distal colon or small intestine of DKO mice. Micro-CT of bone revealed reduced trabecular bone volume and thickness, indicating increased bone resorption as a secondary compensatory mechanism. This study highlights the adaptive plasticity of Ca²⁺-regulatory mechanisms and suggests a role for TRPV5 in reabsorbing Ca²⁺ from the proximal colon and cecum when upstream mechanisms of Ca²⁺ absorption are impaired.
Prenatal Vitamin D, childhood wheeze, asthma, and lung function: Results from the Vitamin D Antenatal Asthma Reduction Trial (VDAART).
Litonjua AA, Weiss ST
J Steroid Biochem Mol Biol · 2026 Jul · PMID 41966490 · Full text
This review article summarizes the main results of the Vitamin D Antenatal Asthma Reduction Trial. This work was presented at the 2025 Vitamin D Workshop.
This review article summarizes the main results of the Vitamin D Antenatal Asthma Reduction Trial. This work was presented at the 2025 Vitamin D Workshop.
New insights into prostate cancer progression: A focus on vitamin D signaling.
Friedrich V, Laverny G
J Steroid Biochem Mol Biol · 2026 Jul · PMID 41962639 · Publisher ↗
Prostate cancer (PCa) is one of the most frequent cancer in men of western society. Whereas the therapeutic options for localized PCa are efficient, those for advanced forms lead to resistance and are of a poor outcome....
Prostate cancer (PCa) is one of the most frequent cancer in men of western society. Whereas the therapeutic options for localized PCa are efficient, those for advanced forms lead to resistance and are of a poor outcome. Thus, it is of utmost importance to understand the mechanisms underlying PCa progression to identify biomarkers predicting tumor evolution and novel therapeutic options. This review summarizes the current knowledge on PCa progression, treatments and preclinical approaches, with a specific emphasis on the role of vitamin D signaling.
Biological and physiological properties of 7-ketocholesterol and interest in diseases and food industry.
Lizard G, Soucek P, Muccioli G … +1 more , Poirot M
J Steroid Biochem Mol Biol · 2026 Jul · PMID 41962638 · Publisher ↗
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3-Epimer-25-hydroxyvitamin D3 interference in assays for the measurement of 25-hydroxyvitamin D3.
Shaw AN, Williams EL
J Steroid Biochem Mol Biol · 2026 Jul · PMID 41962637 · Publisher ↗
In chromatographic measurements of vitamin D, such as liquid chromatography tandem mass spectrometry (LC-MS/MS), 3-epi-25hydroxyvitamin D3 (3-epi-25OHD3) can interfere with 25-hydroxyvitamin D3 (25OHD3) quantification du...
In chromatographic measurements of vitamin D, such as liquid chromatography tandem mass spectrometry (LC-MS/MS), 3-epi-25hydroxyvitamin D3 (3-epi-25OHD3) can interfere with 25-hydroxyvitamin D3 (25OHD3) quantification due to their identical mass. Chromatographic separation is therefore required to overcome this issue. In October 2024, the Vitamin D External Quality Assessment Scheme (DEQAS) distributed two serum samples: 664 (without exogenous 3-epi-25OHD3) and 665 (with 50 nmol/L of added 3-epi-25OHD3). Sample 664 yielded consistent results across 445 labs, giving an Trimmed Mean (ALTM) = 45.6 ± 6.1 nmol/L (±SD, CV = 13.5%), aligning with the Centers for Disease Control and Prevention (CDC) reference value of 46.7 nmol/L. In contrast, sample 665 showed a higher ALTM of 62.1 ± 27.2 nmol/L (±SD, CV = 43.9%) when compared to the CDC target value, with significant variability observed. Most automated immunoassays did not detect 3-epi-25OHD3, except for Roche Gen III (91% cross-reactivity) and Beckman DxI (39.8%). Among 90 LC-MS/MS laboratories reporting #665, 18 routinely measured 3-epi-25OHD3; 15 of these excluded it from their reported total 25OHD (method mean = 47 nmol/L) and 3 included 3-epi-25-OHD3, despite measuring both metabolites separately. The LC-MS/MS results showed a bimodal distribution, with 40 LC-MS/MS laboratories (44%) resolving the epimer chromatographically and 50 LC-MS/MS laboratories (56%) not effectively separating the epimer, leading to overestimation. This positive interference may have clinical implications, especially in neonates who naturally have high 3-epi-25OHD3 levels. Although its biological role remains unclear, current consensus advises excluding 3-epi-25OHD3 from total 25OHD when assessing vitamin D status.
Vitamin D deficiency in Mongolian pregnant women.
Uush T
J Steroid Biochem Mol Biol · 2026 Jul · PMID 41956170 · Publisher ↗
OBJECTIVE: We aimed to estimate the prevalence of vitamin D deficiency in Mongolian pregnant women at the National level as part of the Fifth National Nutrition Survey 2016. DESIGN AND SETTING: This was a cross - section...
OBJECTIVE: We aimed to estimate the prevalence of vitamin D deficiency in Mongolian pregnant women at the National level as part of the Fifth National Nutrition Survey 2016. DESIGN AND SETTING: This was a cross - sectional survey, conducted between September and November in 21 Aimags of 4 economic regions of the country, and in Ulaanbaatar. Given the regional differences in lifestyle and nutritional status, the target populations were stratified into 5 strata based on their economic region and in Ulaanbaatar, with equal samples drawn from each stratum using a cluster - randomized sampling design. A representative sample of 30 clusters was randomly selected using Probability Proportional to Size [PPS] methodology in each of the 4 regions and Ulaanbaatar for a total of 150 cluster units. The selection of survey participants differed for the three sampling regions. Household eligibility was based on having a child 0-59 months of age, living in the household which was randomly selected from each cluster for a total of 450 households in each region. Households with a child 0-59 months of age were selected from household lists available at the kheseg or Bagh level. All pregnant women were selected randomly from Soum and Khoroo family health center antenatal care registries who were mothers of a family with children aged from 0 to 5 years old. PARTICIPANTS: We conducted a cross - sectional survey evaluation of 924 pregnant women who were mothers of a family with children 0-5 years old. MAIN OUTCOME MEASURES: Serum concentration of 25 - hydroxyvitamin D [25(OH)D] were measured using an enzyme-linked fluorescence assay. RESULTS: The overall prevalence of vitamin D deficiency was 75.4% (95% CI 72.2-78.4) with no significant difference in the prevalence of vitamin D deficiency by age group, economic region, area, location, education, ethnicity and body height statuses. Also, prevalence of vitamin D deficiency was 71.9% (95% CI 60.3-81.1), 77.5% (95% CI 60.3-81.6) and 74.2% (95% CI 69.2-78.7) in the first trimester, second trimester and third trimester of pregnancy with no significant difference in the prevalence of vitamin D deficiency between the trimesters of pregnancy. Only 7.3% of pregnant women took a specific vitamin D supplement, with 31.5% of these starting in the first trimester and 60.9% of pregnant women starting supplementation in the second trimester. There is currently no vitamin D food fortification in Mongolia, and oral vitamin D intake across the whole population is very low. The findings of this survey showed that vitamin D deficiency in pregnant women is a public health problem in Mongolia. In conclusion, vitamin D deficiency and low vitamin D status are common in Mongolian pregnant women, which indicated the essential need to include vitamin D screening with adverse maternal and fetal outcomes, and a requirement needed to implement empirical vitamin D supplementation programs before food fortification with vitamin D.
Canagliflozin alleviates hyperandrogen-induced granulosa cell ferroptosis in polycystic ovary syndrome mice by activating the AMPK/GSK3β/NRF2 pathway.
Lin J, Cheng W, Liu Y … +6 more , Zhang Z, Zhou W, Wang Y, Yu H, Qi Y, Yan S
J Steroid Biochem Mol Biol · 2026 Jul · PMID 41956169 · Publisher ↗
Polycystic ovary syndrome (PCOS) is a common metabolic disorder affecting women of reproductive age. Clinical evidence suggests that the SGLT2 inhibitor canagliflozin has potential therapeutic effects in PCOS; however, i...
Polycystic ovary syndrome (PCOS) is a common metabolic disorder affecting women of reproductive age. Clinical evidence suggests that the SGLT2 inhibitor canagliflozin has potential therapeutic effects in PCOS; however, its mechanisms remain unclear. The hyperandrogenic state in patients with PCOS leads to disrupted iron metabolism and oxidative stress. Herein, we aimed to investigate whether canagliflozin ameliorates PCOS symptoms by reducing oxidative stress and inhibiting granulosa cell ferroptosis, as well as to elucidate the underlying mechanisms. We found that canagliflozin treatment significantly restored the estrous cycle, improved polycystic ovarian morphology, reduced serum testosterone levels, and alleviated metabolic disorders, such as insulin resistance and dyslipidemia, in PCOS-like mice. Mechanistically, canagliflozin activated the AMPK/GSK3β pathway, promoted NRF2 nuclear translocation, upregulated GPX4, and ultimately inhibited lipid peroxidation and mitochondrial damage, thereby attenuating hyperandrogen-induced ferroptosis. These results reveal that canagliflozin exerts protective effects via the AMPK/GSK3β/NRF2 axis, thereby offering a potential alternative for PCOS treatment and identifying a promising drug target for clinical intervention.
Molecular biochemistry of soluble epoxide hydrolase in lipid mediator pathways and neuroinflammatory responses.
Verma S, Paliwal S, Dubey P … +4 more , Kaushik S, Joshi R, Dwivedi J, Sharma S
J Steroid Biochem Mol Biol · 2026 Jul · PMID 41956168 · Publisher ↗
Soluble epoxide hydrolase (sEH) is a key enzyme in epoxy fatty acid (EpFA) metabolism, significantly affecting the balance of lipid mediators and the health of the central nervous system (CNS). This review explains the m...
Soluble epoxide hydrolase (sEH) is a key enzyme in epoxy fatty acid (EpFA) metabolism, significantly affecting the balance of lipid mediators and the health of the central nervous system (CNS). This review explains the molecular biology, enzymatic activity, and clinical importance of sEH, emphasizing its role in converting anti-inflammatory epoxygenase metabolites into less active diols. Blocking sEH increases EpFA availability, leading to protective effects in experimental models of neuroinflammation, oxidative stress, and vascular failure linked to Alzheimer's, Parkinson's, and traumatic brain injury. The pharmacokinetics and chemistry of urea- and amide-based sEH inhibitors are also reviewed to highlight their development as potential CNS-targeted treatments. Recent preclinical and early clinical studies indicate that sEH inhibition may slow neurodegeneration and improve synaptic plasticity, thereby enhancing cognitive and behavioral functions. Overall, this review combines biochemical and pharmacological insights to support sEH as a promising target for treating neuroinflammation and neurodegenerative diseases characterized by disrupted lipid mediator signaling.
Developmental-vitamin D deficiency epigenetically regulates cell cycling genes in the embryonic mesencephalon via DNA methylation.
Cui X, Pertile RAN, Alexander S … +2 more , Ali A, Eyles D
J Steroid Biochem Mol Biol · 2026 Jul · PMID 41951130 · Publisher ↗
Epidemiological studies have shown developmental vitamin D (DVD)-deficiency increases the risk of later onset of schizophrenia, and animal models reveal that DVD-deficiency impairs dopaminergic neuron maturation. In cont...
Epidemiological studies have shown developmental vitamin D (DVD)-deficiency increases the risk of later onset of schizophrenia, and animal models reveal that DVD-deficiency impairs dopaminergic neuron maturation. In contrast, vitamin D treatment promotes dopaminergic neuron differentiation in cellular models. Vitamin D also modulates DNA methylation. This study investigates whether maternal vitamin D status influences differentiation of the dopamine-rich ventral mesencephalon via this epigenetic process. Mesencephalon was examined from both DVD-deficient rat dams at gestational day (GD) 14 and dams to which the active form of vitamin D was administered at GD 13. We show that from a panel of DNA methylation or demethylation enzymes, DVD-deficiency increased, whilst vitamin D decreased DNMT3A expression. We then examined the effects of increasing or decreasing DNMT3A on dopaminergic and cell cycle-related genes in mesencephalic neural cultures. DNMT3A overexpression reduced expression of cyclin D1 (CCND1) and CDKN1A (P21), while silencing DNMT3A increased expression of these important cell-cycling genes. Methylation analysis of the promoters of these genes revealed heightened cytosine methylation (5mC) at CCND1 and CDKN1A promoters in DVD-deficient embryos, but vitamin D treatment had no direct impact on these methylation patterns. We conclude that DVD-deficiency's adverse effects on early brain development may be due to heightened methylation of important cell cycle genes via increased DNMT3A. Although the active form of vitamin D decreased DNMT3A expression in utero, the absence of any silencing effect on these same cell cycle genes suggests this hormone may affect early brain differentiation via more direct transcriptional regulatory pathways via its canonical receptor.
Cisplatin-resistant A549 non-small cell lung cancer cells sensitivity to 7-ketocholesterol.
Gonet-Surówka A, Dynarowicz-Latka P
J Steroid Biochem Mol Biol · 2026 Jun · PMID 41903765 · Publisher ↗
Lung cancer is the most common cancer worldwide. It is often detected in the late stages of the disease and is difficult to treat. Furthermore, the cancer often develops resistance to chemotherapy drugs such as cisplatin...
Lung cancer is the most common cancer worldwide. It is often detected in the late stages of the disease and is difficult to treat. Furthermore, the cancer often develops resistance to chemotherapy drugs such as cisplatin. This study aimed to compare the sensitivity of two variants of the A549 cell line: sensitive and resistant to cisplatin, to the action of 7-ketocholesterol. A549 cells were exposed to cisplatin for several weeks to generate a cisplatin-resistant subpopulation. They were then exposed to various concentrations of 7-ketocholesterol. The effect of 7-ketocholesterol on cell viability, apoptosis, and reactive oxygen species was examined. The results for both variants of the A549 cell line subpopulations demonstrated a slightly greater sensitivity of the cisplatin-resistant subpopulation to 7-ketocholesterol. These are preliminary, pilot studies that pave the way for more advanced research on the effects of oxysterols on chemotherapy-resistant cancer cells.
Comparative study of four matrix effect correction strategies for bile acid quantification in mouse serum.
Xie M, Guo X, Shen S … +1 more , Zhang M
J Steroid Biochem Mol Biol · 2026 Jun · PMID 41895385 · Publisher ↗
Endogenous substances are components produced by metabolism within the body, and they play a crucial role in disease diagnosis, treatment, and the regulation of physiological functions. However, it is difficult to obtain...
Endogenous substances are components produced by metabolism within the body, and they play a crucial role in disease diagnosis, treatment, and the regulation of physiological functions. However, it is difficult to obtain a blank matrix or substitute analytes, which leads to uncertainties in quantitative analysis. Common analytical strategies for evaluating matrix effects include standard addition, background subtraction, surrogate analyte, and surrogate matrix. It requires experimental studies to comprehensively compare these four strategies. This study employed three different types of serum matrices: authentic serum, artificial serum, and serum treated with activated carbon at different concentrations. Common endogenous compounds (bile acids) were selected as representative analytes, and quality control samples were prepared. calibration standard curves were established and calibrated according to the different analytical strategies. The four strategies were then comprehensively compared by evaluating the accuracy, precision, and matrix effects. The results demonstrated that the treatment method using activated carbon adsorption (at 0.1 g/mL) performed the best. Furthermore, based on the comparison of the four strategies, a complete method validation was performed for fifteen common bile acids, and the results met all the requirements for detection and analysis. This study provides an important reference for the absolute quantitative analysis of endogenous substances.
Vitamin D in major depressive disorder: Current evidence, possible molecular mechanisms, and future prospects.
Camargo A, Rodrigues ALS
J Steroid Biochem Mol Biol · 2026 Jun · PMID 41895384 · Publisher ↗
Vitamin D signaling has emerged as a significant modulator of neurobiological processes implicated in major depressive disorder (MDD). Beyond its classical functions in calcium homeostasis and bone health, accumulating e...
Vitamin D signaling has emerged as a significant modulator of neurobiological processes implicated in major depressive disorder (MDD). Beyond its classical functions in calcium homeostasis and bone health, accumulating evidence highlights antioxidant, neurotrophic, and anti-inflammatory effects mediated by vitamin D-dependent pathways in the central nervous system. By influencing neurotransmitter synthesis, neuroinflammatory and redox pathways, as well as neuroplasticity, vitamin D signaling may contribute to mechanisms underlying depressive symptoms. Therefore, this review aims to provide a comprehensive overview of preclinical studies examining the association between vitamin D status or vitamin D-related interventions and antidepressant-like effects in rodent models, exploring the molecular mechanisms potentially involved, and highlighting the role of vitamin D-dependent signaling pathways in modulating key neurobiological targets implicated in MDD. It may contribute to establishing the relevance of vitamin D-related mechanisms to MDD pathophysiology and identifying promising targets for future translational studies.
A DEQAS review of the current performance of assays for the measurement of 1,25dihydroxyvitamin D.
Hackney GE, Williams EL
J Steroid Biochem Mol Biol · 2026 Jul · PMID 41887371 · Publisher ↗
The Vitamin D External Quality Assessment Scheme (DEQAS) evaluates participants' performance of analytical methods for vitamin D metabolites, including 1,25dihydroxyvitamin D (1,25(OH)D), by distributing samples globally...
The Vitamin D External Quality Assessment Scheme (DEQAS) evaluates participants' performance of analytical methods for vitamin D metabolites, including 1,25dihydroxyvitamin D (1,25(OH)D), by distributing samples globally on a quarterly basis. In this review an assessment of the performance of current 1,25(OH)D methods is presented. Data submitted by scheme participants for the 2024/25 DEQAS distribution cycle was analysed and trends between assays were compared. The four distributions across the 2024/25 DEQAS cycle covered a wide concentration range, challenging participants to report results across the full reference interval. Analytical performance is improving; however, variation persists between the major method groups. Participation in an accuracy-based scheme is considered the gold standard, but there is currently no reference measurement procedure available for 1,25(OH)D. Participant performance is therefore assessed against the Method Laboratory Trimmed Mean (MLTM). To evaluate the validity of this approach, measurement uncertainty was calculated for each method and for the All Laboratory Trimmed Mean (ALTM) across all of the distributions of the 2024/25 cycle. Calculated measurement uncertainty fell within the limits of acceptability (less than 30% of standard deviation) for the ALTM, and for the MTLM of DiaSorin Liaison XL group. For method groups with fewer participants, the uncertainty of the MLTM as a target value fell outside the limits of acceptability, confirming that the ALTM offers a more robust target value. This finding supports the use of the ALTM for assessing participants' performance, with acceptable performance being defined as the ALTM ± 30%, in at least 80% of distributed samples. This performance target represents what can be achieved with the current 'state of the art' of methods for 1,25(OH)D measurement.
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