The Journal Of Steroid Biochemistry And Molecular Biology[JOURNAL]
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200 papers
Effects of repeated administration of oxandrolone in female wistar rats undergoing strength training.
Marin E, Torres NV, Severo MMR … +9 more , Santos NG, Cattani S, Rossato-Grando LG, Dallegrave E, Leal MB, Gomez R, Garcia SC, Arbo MD, Arbo BD
J Steroid Biochem Mol Biol · 2026 Apr · PMID 41620041 · Publisher ↗
Anabolic androgenic steroids are synthetic derivatives of testosterone that mimic its actions in various tissues. Due to its strong anabolic activity, weak androgenic effects, and resistance to hepatic metabolism, oxandr...
Anabolic androgenic steroids are synthetic derivatives of testosterone that mimic its actions in various tissues. Due to its strong anabolic activity, weak androgenic effects, and resistance to hepatic metabolism, oxandrolone is one of the most commonly used anabolic steroids among female athletes. This study aimed to evaluate the anabolic effects of oxandrolone and its toxicological profile in female rats subjected to a strength training protocol. A total of 24 female Wistar rats (60 days old) were randomly assigned to receive oxandrolone (1.77 mg/kg/day) or its vehicle (corn oil) (n = 12 per group) via daily gavage for 28 days. The exercise protocol consisted of six climbs on an inclined ladder, with two climbs per workload (50 %, 75 %, and 100 % of each animal's maximum load) performed three times per week. Investigators remained blinded throughout experimentation and data analysis. Oxandrolone did not significantly affect body weight gain, relative organ and muscle mass, or muscle strength. However, it altered mean corpuscular volume, eosinophil count, and urea levels. Additionally, liver TBARS levels increased, while no changes were observed in plasma lipid peroxidation, antioxidant enzyme activity, total non-protein thiol levels, or mitochondrial respiratory chain complex activity. Histopathological analysis revealed oxandrolone-induced damage to cardiac and skeletal muscle, along with structural alterations in the spleen and adrenal gland. Given its limited effect on muscle strength, along with histopathological changes and increased liver lipoperoxidation, these findings raise concerns about oxandrolone use in healthy individuals seeking aesthetic or athletic benefits.
E3 ubiquitin ligase PELI1 promotes ferroptosis in granulosa cells in PCOS by degrading Fth1.
Zha X, Chen L, Tan Z … +8 more , Wu T, Xiong Q, Wang H, Kuang Y, Xing F, Lu A, Sun L, Zhang Y
J Steroid Biochem Mol Biol · 2026 May · PMID 41620040 · Publisher ↗
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women of reproductive age, characterized by hyperandrogenemia and obstruction of ovulation. However, the underlying mechanisms of ovarian abn...
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women of reproductive age, characterized by hyperandrogenemia and obstruction of ovulation. However, the underlying mechanisms of ovarian abnormalities in PCOS remain to be investigated. In this study, we first identified altered levels of ovarian ferroptosis in the PCOS population by screening a web-based database. Further, we established a prasterone-exposed PCOS mouse model and a granulosa cell model to confirm that hyperandrogenism can lead to the development of ferroptosis in ovarian granulosa cells. The transcriptome sequencing and cellular experiments were conducted to explore the possible mechanisms. It was found that the ubiquitination pathway and P53 pathway are significantly enriched in the prasterone-exposed granulosa cells. The E3 ubiquitin ligase PELI1 gene is significantly highly expressed in PCOS ovaries and may contribute to ferroptosis by degrading FTH1. In addition, high expression of the P53 gene was associated with alterations in PELI1/FTH1. This study confirmed that hyperandrogenism can mediate the development of ovarian ferroptosis via the P53/PELI1/FTH1 pathway and the E3 ubiquitin ligase PELI1 plays an important regulatory role. In vivo, the iron death inhibitor deferoxamine mesylate could alleviate ferroptosis and follicular development disorder in the ovaries of PCOS mice. This study provides new insights into the pathological changes of PCOS ovaries and possible interventions for the treatment of PCOS.
Androgen production in adrenocortical H295R cells is regulated by thyroid hormone T3 without reciprocal thyroid axis modulation in pediatric CAH.
Augsburger P, du Toit T, Altinkiliç EM … +5 more , Hannema S, de Bruin C, Charmandari E, van den Akker ELT, Flück CE
J Steroid Biochem Mol Biol · 2026 Apr · PMID 41544797 · Publisher ↗
Thyroid hormones (THs) are critical regulators of human development, cellular differentiation, and metabolism. While their systemic effects are well established, their role in adrenal androgen production remains poorly d...
Thyroid hormones (THs) are critical regulators of human development, cellular differentiation, and metabolism. While their systemic effects are well established, their role in adrenal androgen production remains poorly defined. Moreover, potential feedback regulation of the hypothalamic-pituitary-thyroid (HPT) axis by adrenal androgens has not been thoroughly investigated. This study aimed to clarify the regulatory effects of THs on adrenal androgens and to investigate potential feedback mechanisms in patients with congenital adrenal hyperplasia (CAH). In an in-vitro experiment, treatment with 3,3',5-triiodo-L-thyronine (T3) on adrenocortical carcinoma H295R cells significantly reduced dehydroepiandrosterone (DHEA) and DHEA-sulfate production while modestly increasing testosterone (T) and androstenedione (A4). These changes were associated with an increase in expression of HSD3B2 and AKR1C3, and a decrease of CYP17A1. Transcriptomic analysis additionally revealed enrichment of pathways related to steroidogenesis and adrenal development through T3 treatment. In the clinical part of the study, hormone levels in pediatric CAH patients were analyzed. Serum free thyroxine (fT4) and thyroid-stimulating hormone (TSH) showed weak negative correlations with the adrenal androgens DHEA and A4. However, no differences in fT4 or TSH concentrations were observed between well-controlled and hyperandrogenic patients, suggesting a lack of feedback regulation by adrenal androgens on the HPT axis. In conclusion, these findings suggest that THs regulate adrenal androgen production by modulating the activity of key steroidogenic enzymes. This relationship appears to be predominantly unidirectional, with THs influencing adrenal steroidogenesis but adrenal androgens not altering HPT axis function.
Serum steroid profiling by LC-MS/MS in distinguishing adrenocortical carcinoma from other indeterminate adrenal masses.
Rao A, Phadte A, Ban A … +13 more , Memon SS, Karlekar M, Lila AR, Sarathi V, Kansal N, Barnabas R, Badhe PV, Fernandes G, Rege S, Prakash G, Menon S, Shah N, Bandgar T
J Steroid Biochem Mol Biol · 2026 Apr · PMID 41544796 · Publisher ↗
For an adrenal incidentaloma with indeterminate imaging characteristics, urine multisteroid profiling is suggested for diagnosing adrenocortical carcinoma (ACC). Data on the utility of serum steroid metabolomics in this...
For an adrenal incidentaloma with indeterminate imaging characteristics, urine multisteroid profiling is suggested for diagnosing adrenocortical carcinoma (ACC). Data on the utility of serum steroid metabolomics in this context is limited to a few studies. Here, we present data of 62 adult patients with indeterminate unilateral adrenal masses (size ≥ 3 cm and basal attenuation ≥10HU) where baseline serum liquid chromatography-tandem mass spectrometry (LC-MS/MS) multisteroid profiling was available. Logistic regression was used to identify the key steroid signature for differentiating ACC from other non-ACC adrenal masses. Among 62 patients (median age: 41 years, 31 males), 37 (59.6 %) had ACC. The non-ACC cohort (n = 25) comprised pheochromocytoma (n = 9), adrenocortical adenoma (n = 8), metastases (n = 4), schwannoma (n = 2), ganglioneuroma (n = 1), and lymphoma (n = 1). Tumour size was significantly larger in the ACC cohort (9.9 vs 7.0 cm; p < 0.001) than the non-ACC cohort. Nine of 13 steroids were significantly elevated in ACC: 11-deoxycorticosterone (DOC), 17-hydroxyprogesterone (17OHP), 11-deoxycortisol (S), cortisone (E), androstenedione (A4), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulphate (DHEAS) in both sexes, as well as testosterone (T) in females and progesterone (P4) in males. After excluding sex-dependent steroids, univariate analysis yielded six significant steroids (17OHP, S, E, A4, DHEA, and DHEAS). A multivariate logistic regression model with backward elimination identified A4, S, and DHEAS as the best discriminators (AUC:0.923), with a cutoff of 0.52 yielding 83.8 % sensitivity and 96 % specificity for diagnosing ACC. Our study results suggest serum LC-MS/MS profiling of three steroids (A4, S, and DHEAS) provides a non-invasive approach to distinguish ACC from other indeterminate adrenal masses.
Anabolic-androgenic steroids at supraphysiological doses: Cardiovascular impacts and pathophysiological mechanisms.
Nascimento HS, Corrêa MG, Lemos OL … +2 more , Lima HN, Amaral LSB
J Steroid Biochem Mol Biol · 2026 Apr · PMID 41539555 · Publisher ↗
This narrative review explores the cardiovascular risks associated with the non-therapeutic use of anabolic-androgenic steroids (AAS) at supraphysiological doses. Initially indicated for clinical conditions like hypogona...
This narrative review explores the cardiovascular risks associated with the non-therapeutic use of anabolic-androgenic steroids (AAS) at supraphysiological doses. Initially indicated for clinical conditions like hypogonadism and anemia, AAS are increasingly misused for aesthetic and performance enhancement, often at doses far exceeding therapeutic recommendations. Through a literature review of 34 studies selected from PubMed (2015-2025), the review analyzes the molecular mechanisms and cardiovascular consequences of high-dose AAS use. Genomic and non-genomic pathways, along with modulation of the IGF-1 axis, underlie alterations in gene expression and cellular metabolism that lead to myocardial remodeling, hypertension, dyslipidemia, thrombosis, endothelial dysfunction, and systemic inflammation. These effects are further intensified by behavioral factors such as polypharmacy and substance abuse. Despite ethical limitations on clinical trials with supraphysiological doses, experimental and epidemiological data consistently suggest that excessive AAS use significantly elevates the risk of adverse cardiovascular events. This work highlights the urgent need for public health policies, educational initiatives, and longitudinal studies to assess real-world use patterns and mitigate harms associated with AAS abuse.
Therapeutic potential of dehydroepiandrosterone in early osteoarthritis: Modulating cartilage ECM stiffness through LOX-RhoA/ROCK/MLC signalling - An in vivo study.
Huang K, Cai H, Jiang C … +1 more , Zheng C
J Steroid Biochem Mol Biol · 2026 Apr · PMID 41534800 · Publisher ↗
Osteoarthritis (OA) is characterized by progressive cartilage degeneration and extracellular matrix (ECM) stiffening, yet effective disease-modifying therapies remain limited. This study evaluated the chondroprotective e...
Osteoarthritis (OA) is characterized by progressive cartilage degeneration and extracellular matrix (ECM) stiffening, yet effective disease-modifying therapies remain limited. This study evaluated the chondroprotective effect of dehydroepiandrosterone (DHEA) in early OA and elucidated its underlying mechanisms. Using rabbit and mouse models, we demonstrated that intra-articular DHEA administration attenuated cartilage damage, reduced catabolic enzyme expression, and preserved ECM elasticity. Mechanistically, DHEA downregulated lysyl oxidase (LOX), suppressed activation of the RhoA/ROCK/MLC signaling cascade, and thereby mitigated ECM stiffening. The protective effects were partly dependent on LOX inhibition, suggesting a dual regulatory mechanism. These findings identify DHEA as a potential disease-modifying agent that targets LOX-RhoA/ROCK/MLC signaling to maintain cartilage homeostasis in early OA, warranting further clinical investigation.
Temporal transcriptomic changes during neurodevelopment in a mouse model of Smith-Lemli-Opitz syndrome.
Li A, Tomita H, Xu L
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41506459 · Full text
Smith-Lemli-Opitz syndrome (SLOS) is a cholesterol biosynthesis disorder caused by mutations in the DHCR7 gene, leading to reduced cholesterol production and accumulation of its precursor, 7-dehydrocholesterol. SLOS disp...
Smith-Lemli-Opitz syndrome (SLOS) is a cholesterol biosynthesis disorder caused by mutations in the DHCR7 gene, leading to reduced cholesterol production and accumulation of its precursor, 7-dehydrocholesterol. SLOS displays a wide range of neurodevelopmental defects, intellectual disability, and behavioral problems. However, an in-depth study of the temporal changes in gene expression in developing brains has not been conducted before. In this work, we carried out the transcriptomic analysis of whole brains from WT and Dhcr7-KO mice at embryonic day 12.5 (E12.5), E14.5, E16.5, and postnatal day 0 (PND0). First, we observed the expected downregulation of the Dhcr7 gene in the Dhcr7-KO brains, as well as changes in other genes involved in cholesterol biosynthesis at all time points. Pathway and GO term enrichment analyses revealed affected signaling pathways and biological processes that were shared amongst time points and unique to individual time points. Specifically, pathways important for embryonic and neural development, including Hippo, Wnt, and TGF-β signaling pathways, are most significantly affected at the earliest time point, E12.5. Additionally, neurogenesis-related GO terms were enriched at earlier time points, consistent with the timing of development. Conversely, pathways related to synaptogenesis, which occur later in development than neurogenesis, are significantly affected at the later time points, E16.5 and PND0, including cholinergic, glutamatergic, and GABAergic synapses. In vitro neurogenesis experiments using GABAergic neuronal precursors isolated from embryonic mouse brain confirmed that loss of Dhcr7 led to decreased proliferation and premature neurogenesis, consistent with the transcriptomic changes.
The hexosamine biosynthesis pathway as a potent culprit in breast cancer progression.
Musavi M, Oghbaei F, Abavisani M … +2 more , Ghasemi A, Momtazi-Borojeni AA
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41483845 · Publisher ↗
The hexosamine biosynthesis pathway (HBP) is a nutrient-sensitive branch of glucose metabolism that produces UDP-GlcNAc, a central substrate for protein glycosylation. Growing evidence links altered HBP activity to breas...
The hexosamine biosynthesis pathway (HBP) is a nutrient-sensitive branch of glucose metabolism that produces UDP-GlcNAc, a central substrate for protein glycosylation. Growing evidence links altered HBP activity to breast cancer (BC) progression and treatment response. However, the strength of evidence differs across tumor subtypes and across experimental versus patient data. This review summarizes current clinical and preclinical evidence on how HBP enzymes and HBP-derived glycosylation contribute to BC biology. Across BC cohorts and experimental models, increased expression of key HBP components has been associated with aggressive features, while mechanistic studies show that HBP activity can support oncogenic signaling through elevated O-GlcNAcylation of regulatory proteins. Work in BC models further indicates that HBP-related changes influence proliferation, survival, epithelial-mesenchymal transition, migration, and invasion, and may interact with pathways such as PI3K/AKT/mTOR, Wnt/β-catenin, and YAP. Evidence discussed in this review also links HBP output to stress-adaptation programs, including DNA damage responses and ER protein-folding capacity via N-linked glycosylation, which can promote survival under nutrient or therapy stress. Therapeutic studies described here include direct and indirect strategies to reduce HBP output, such as targeting pathway enzymes, modulating O-GlcNAc cycling, and using hexosamine analogs designed to disrupt flux or glycan function; these approaches reduce growth and metastatic behavior in several preclinical settings, but specificity and normal-tissue tolerance remain key constraints. Overall, the literature supports HBP as a plausible metabolic contributor to BC progression, but stronger patient-linked validation is needed. Future work should prioritize subtype-resolved clinical studies and direct measures of pathway activity to guide biomarker development and therapeutic targeting.
Design, synthesis, and biological evaluation of novel steroidal selenosemicarbazone derivatives as potent antitumor agents.
Gan C, Gan B, Li Y … +5 more , Huang Y, Liu Z, Gu Y, Chen H, Lin Q
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41482078 · Publisher ↗
The development of novel chemotherapeutic agents with high efficacy and low toxicity remains a critical challenge in oncology. In this study, a novel series of steroidal selenosemicarbazone derivatives were designed and...
The development of novel chemotherapeutic agents with high efficacy and low toxicity remains a critical challenge in oncology. In this study, a novel series of steroidal selenosemicarbazone derivatives were designed and synthesized through the selenium functionalization of diverse steroid scaffolds. Key ketone intermediates derived from cholesterol, dehydroepiandrosterone (DHEA), estrone, and pregnenolone were condensed with various selenosemicarbazides to achieve structural diversification across the steroid nucleus. The antiproliferative activities of the synthesized compounds were evaluated against a panel of human cancer cell lines. Most compounds exhibited broad-spectrum cytotoxicity, among which compound 17c, based on the DHEA scaffold, showed superior potency against MCF-7 breast cancer cells(IC = 4.80 ± 0.43 μM)and high selectivity over normal cells. Mechanism-of-action studies revealed that 17c induces mitochondrial-mediated apoptosis, characterized by the loss of mitochondrial membrane potential, activation of caspase-9, and G2/M phase cell cycle arrest. Molecular docking simulations implicated glutathione reductase (GR) as a potential molecular target, suggesting that the binding of 17c to GR may initiate the observed mitochondrial dysfunction. Furthermore, the concentration-dependent suppression of cell proliferation, migration, and clonogenic survival by 17c was confirmed through a suite of functional assays. Collectively, this work identifies 17c as a promising lead compound with a clarified mechanistic profile for the development of efficient and low-toxicity anticancer agents.
Exploring the feature prioritization and data sampling of PCOS diagnosis via densely connected attention based squeeze deep learning detection model.
Pulluparambil SJ, Subrahmanya Bhat
J Steroid Biochem Mol Biol · 2026 Apr · PMID 41482077 · Publisher ↗
Accurate and timely diagnosis remains a challenge due to the complexity of Polycystic Ovary Syndrome (PCOS) symptoms and data imbalance issues in the existing datasets. This research aims to develop a robust PCOS detecti...
Accurate and timely diagnosis remains a challenge due to the complexity of Polycystic Ovary Syndrome (PCOS) symptoms and data imbalance issues in the existing datasets. This research aims to develop a robust PCOS detection model that addresses these challenges by introducing a novel hybrid methodology with effective feature prioritization while handling data balancing issues. The research involves three major phases: pre-processing, feature selection, and PCOS detection. In the pre-processing stage, dataset balancing is emphasized by the combination of Synthetic Minority Oversampling Techniques (SMOTE) and Edited Nearest Neighbor (ENN). Under this stage, replacing null values, balancing the dataset, and dropping unnecessary columns are accomplished to increase PCOS detection accuracy. The second stage is feature selection, where a distinct hybrid bionic strategy named the Gorilla Salp Swarm Troop Model (GS2TM) is proposed to pick the optimal set of dominant features. The GS2TM algorithm reduces the feature set by 51.1 %, retaining only 23 features while achieving a state-of-the-art accuracy of 98.7 %. In addition, the Densely Connected Attention-Based Squeeze Convolutional Detection Model (DASCD) is proposed for the prediction of PCOS, in which multiple layers are adjusted in a feed-forward manner. The novelty of this work lies in the unified pipeline that simultaneously addresses three major challenges in PCOS detection, such as dataset imbalance (SMOTE-ENN), feature redundancy (GS2TM), and overfitting (DASCD with attention), providing both high accuracy and enhanced interpretability. As a result, the proposed detection model greatly improves accuracy compared to other existing ML-based strategies. Specifically, by utilizing 23 characteristics with GS2TM, the proposed model outperforms with an accuracy of 98.7 % in categorizing PCOS and non-PCOS.
Seasonal variation of prostatic steroid hormone synthesis capacity in wild ground squirrels (Spermophilus dauricus).
Chen P, Gao Q, Xie W … +4 more , Yu H, Liu Y, Zhang H, Weng Q
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41482076 · Publisher ↗
Our previous studies showed that the prostates of the wild ground squirrels were capable of locally synthesizing testosterone (T), dihydrotestosterone (DHT) and estrogen. In this study, we investigated expression levels...
Our previous studies showed that the prostates of the wild ground squirrels were capable of locally synthesizing testosterone (T), dihydrotestosterone (DHT) and estrogen. In this study, we investigated expression levels of luteinizing hormone receptor (LHR), steroidogenic factor 1 (SF-1), steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase (3βHSD) and 17α-hydroxylase cytochrome P450 (P450c17) in the prostates of the wild ground squirrels during the breeding and non-breeding seasons. LHR, SF-1, StAR, P450scc, 3βHSD and P450c17 were identified in the stromal cells or epithelial cells. The mRNA expression levels of LHR, SF-1, StAR, P450scc, P450c17, 3βHSD and Sterol Regulatory Element-Binding Protein 2 (Srebp2) in the prostate were remarkedly higher during the breeding period than those in the non-breeding period. In contrast, the mRNA expression levels of Melatonin Receptor 1a (Mtnr1a) and Melatonin Receptor 1b (Mtnr1b) were elevated during the non-breeding period. Consistently, the circulating LH and T as well as the prostatic T and DHT concentrations were remarkably higher in the breeding season than those of the non-breeding season, which were positively correlated with the seasonal changes of prostatic weight. Additionally, the transcriptomic study in the prostates identified that differentially expressed genes might be related to signal transduction and signaling receptor activity using GO analysis. The KEGG pathway enriched by differentially expressed genes detected to be involved in steroid biosynthesis, estrogen signaling pathway or steroidogenesis. Taken together, these findings suggested that the prostates of the wild ground squirrels potentially owned ability to synthesize steroid hormones de novo, and the steroid hormones might affect the prostatic functions of the wild ground squirrels via an autocrine or paracrine manner.
Vitexin reduced the dihydrotestosterone (DHT)-induced fibrosis in KGN cells by regulating the NR4A1/NLRP3 pathway.
Xu JJ, Yan CZ, Liu ZQ … +7 more , Sun HR, Zhang MY, Huang QP, Tong CX, Pan CX, Song JL, Zhou YY
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41482075 · Publisher ↗
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in women of reproductive age, markedly impairing their health and reducing overall quality of life. Vitexin is a natural flavonoid compound...
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in women of reproductive age, markedly impairing their health and reducing overall quality of life. Vitexin is a natural flavonoid compound that has demonstrated diverse pharmacological properties, including anti-inflammatory and antioxidant effects. The aim of this study was to investigate the effects of vitexin on dihydrotestosterone (DHT)-induced fibrosis in KGN cells, as well as its regulatory role in the NR4A1/NLRP3 signaling pathway. Experimental findings suggested that DHT treatment resulted in decreased cell viability, disrupted sex hormone balance, increased oxidative stress, and elevated levels of inflammation and fibrosis in KGN cells. However, vitexin intervention significantly reversed these pathological changes. Transcriptomics sequencing analysis and molecular docking further indicated that NR4A1 is a pivotal target of vitexin in modulating the inflammatory response. Vitexin significantly inhibited NLRP3 inflammasome-mediated inflammation by activating NR4A1, conversely NR4A1 knockdown partially attenuated the protective effects of vitexin (P < 0.01). Therefore, vitexin was found to effectively ameliorate DHT-induced alterations in cell viability, sex hormone levels, oxidative stress, inflammation and fibrosis in KGN cells. These protective effects appear to be closely related to the regulation of the NR4A1/NLRP3 signaling pathway.
Increased TGF-β signaling during antiestrogen therapy in triple-negative breast cancer cells.
Dharwal N, Rathore D, Shukla N … +1 more , Dave HV
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41482074 · Publisher ↗
Antiestrogen therapies, such as Tamoxifen (TAM), are widely used in managing estrogen receptor-positive (ER+) breast cancer (BC); however, resistance to these agents remains a significant clinical challenge. Triple-negat...
Antiestrogen therapies, such as Tamoxifen (TAM), are widely used in managing estrogen receptor-positive (ER+) breast cancer (BC); however, resistance to these agents remains a significant clinical challenge. Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, lacking approved targeted therapies and exhibiting poor patient outcomes. Transforming growth factor-β (TGF-β), a dual-functional cytokine involved in tumor suppression and progression, has gained attention for its crucial role in breast cancer development and metastasis. Therefore, evaluating the impact of antiestrogens on TGF-β pathway components may help identify novel therapeutic targets for TNBC. This study investigated the expressions of TGF-β1, TGF-β2, and SMAD-3 in four human BC cell lines (MCF-7, MDA-MB-231, MDA-MB-468, and SK-BR-3) following treatment with optimal cell-line-specific doses of TAM and its active metabolite, 4-Hydroxytamoxifen (4-OH-TAM). In TNBC cells, antiestrogen treatment resulted in elevated TGF-β1 expression, accompanied by increased TGF-β2 and SMAD-3, particularly in metastatic MDA-MB-231 cells. Gene expression analysis also revealed that TGF-β1 was upregulated in short-term TAM treatment in MDA-MB-231 cells, whereas 4-OH-TAM had minimal impact. Long-term exposure led to opposite patterns with TGF-β1 decreasing in TAM of MDA-MB-231 cells but increasing in MCF-7 cells, while TGF-β1 elevates in 4-OH-TAM in MDA-MB-231 cells, suggesting cell line and duration-specific responses. Functional assays further showed differential anti-migratory effects, with TAM more effective in MDA-MB-231 and 4-OH-TAM in MCF-7 cells. These findings highlight TGF-β1 as a potential biomarker for TNBC and for predicting responses to antiestrogen therapies, warranting further mechanistic and functional validation.
Molecular targets of ergosterol and its derivatives in cancer therapy: Recent trends and strategies to improve its bioavailability.
Shivali, Kumar H, Agnihotri N
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41482073 · Publisher ↗
Cancer poses a major global health concern, with an alarming increase in incidence and associated mortality. Surgical resection of tumor, radiotherapy and chemotherapy remains the mainstay of therapeutic options availabl...
Cancer poses a major global health concern, with an alarming increase in incidence and associated mortality. Surgical resection of tumor, radiotherapy and chemotherapy remains the mainstay of therapeutic options available. Though these treatments do increase the life span of the patients but severely impact their quality of life due to their short term or long term adverse effects. The current research is therefore focused on exploring the natural compounds as an alternative and indeed many do exhibit anticancer activity. Complex metabolic reprogramming in cancer prompts the need for researchers to explore novel and innovative strategies to target such aberrant pathways by using safer and effective natural products. The present review focusses on Ergosterol, a mycosterol present in mushrooms which not only modulates the aberrant cholesterol homeostasis but also show independent anticancer activity due to its antioxidant, anti-inflammatory and lipid lowering properties. In addition, the challenges and limitations related to its utility as a drug molecule and advancements in improving its pharmacological properties using chemical and physical modifications has also been addressed.
The dual carbonyl reductase activities of 17β-HSD12a during ovarian development in Japanese eel (Anguilla japonica).
Huo P, Chen S, Huang J … +4 more , Yang Y, Bai Z, Xie Y, Lai X
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41478515 · Publisher ↗
17β-hydroxysteroid dehydrogenase subtype 12 (17β-HSD12) is responsible for the reactions between carbonyl and hydroxyl groups at the C17 position of sex steroids. Our previous research revealed that hsd17b12a was express...
17β-hydroxysteroid dehydrogenase subtype 12 (17β-HSD12) is responsible for the reactions between carbonyl and hydroxyl groups at the C17 position of sex steroids. Our previous research revealed that hsd17b12a was expressed at a high level during follicular maturation in Anguilla japonica, peaking at the migrating nucleus stage. This indicated the potential of 17β-HSD12 may convert 17α-hydroxyprogesterone (17OHP) into 17α,20β-dihydroxy-4-pregnen-3-one (DHP), a maturation-inducing steroid. To elucidate the functions of hsd17b12a in A. japonica, the spatiotemporal expression patterns of hsd17b12a were investigated, as well as its role in sex steroid hormone synthesis, and its regulation by upstream gonadotropins. The results showed that hsd17b12a expression was the highest in the ovaries compared to other tissues. Within the ovary, hsd17b12a expression peaked at the migrating nucleus stage, followed by the mid-vitellogenic stage, both significantly higher than other stages. HEK293T cells transfected with a plasmid expressing A. japonica hsd17b12a converted estrone, androstenedione, and 17OHP into 17β-estradiol, testosterone, and DHP, with the conversion rates of 23.70 ± 10.65, 14.95 ± 4.42, and 22.35 ± 0.53 %, respectively. In vitro experiment showed that stimulation with 10 ng/mL 17OHP and 100 µg/mL carp pituitary extract greatly significantly increased hsd17b12a expression of follicles with migrating nucleus stage, although DHP synthesis did not change significantly. The present study demonstrates that the enzyme encoded by eel hsd17b12a possesses both C17 and C20 carbonyl reductase activities. These findings provide new insights into the reproductive endocrine regulatory mechanisms and offer theoretical support for optimizing artificial maturation and spawning in eels.
The multi-target mechanisms of β-sitosterol in Alzheimer's disease: Integrative evidence from network pharmacology, molecular docking, and mendelian randomization.
Zhang M, Huang Y, Du W … +5 more , Lu T, Ye L, Cheng X, Zeng X, Sun J
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41448363 · Publisher ↗
β-Sitosterol, a widely distributed phytosterol, has shown therapeutic potential against Alzheimer's disease (AD); however, its system-level mechanisms remain unclear. This study aimed to generate testable hypotheses rega...
β-Sitosterol, a widely distributed phytosterol, has shown therapeutic potential against Alzheimer's disease (AD); however, its system-level mechanisms remain unclear. This study aimed to generate testable hypotheses regarding β-sitosterol activity in AD using an integrative computational framework. Potential targets were predicted using SwissTargetPrediction and were intersected with AD-related genes. Core targets were identified via protein-protein interaction network analysis, followed by pathway enrichment and validation using Gene Expression Omnibus transcriptomic datasets. Binding interactions were evaluated using molecular docking and 100-ns molecular dynamics (MD) simulations. Mendelian randomization (MR) was used to assess the causal association between circulating estradiol levels (proxy for aromatase activity) and AD risk. Nineteen potential targets were identified, with core genes (e.g., CYP19A1, ESR1, and NR3C1) significantly enriched in steroid hormone biosynthesis pathways. Β-Sitosterol exhibited strong binding affinities to CYP19A1 (-9.7 kcal/mol) and ESR1 (-8.2 kcal/mol), and MD simulations confirmed β-sitosterol-CYP19A1 complex stability. Differential expression analysis validated the dysregulation of key targets in AD. MR analysis further indicated that genetically predicted higher estradiol levels were significantly associated with reduced AD risk (IVW: β = -11.02, SE = 2.77, p = 6.78 × 10⁻⁵). This study provides predictive evidence that β-sitosterol may influence AD pathology by modulating steroidogenic enzymes and hormone signaling. However, as all findings were computationally derived and estradiol serves only as an indirect proxy for aromatase activity, experimental validation is required to confirm these proposed mechanisms. Our results offer a hypothesis-generating framework for further investigation of β-sitosterol as a multitarget candidate for AD.
Bisphenol A derivatives as potent inhibitors of 11β-hydroxysteroid dehydrogenase 2: A structure-activity study.
Ren X, Shi L, Chen X … +4 more , Tang Y, Ying Y, Ge R, Zhu Q
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41418946 · Publisher ↗
Bisphenol A (BPA) has been restricted for its use due to endocrine-disrupting effects and its benzene-ring-substituted derivatives (BPADs) are increasingly used. However, their effects on 11β-hydroxysteroid dehydrogenase...
Bisphenol A (BPA) has been restricted for its use due to endocrine-disrupting effects and its benzene-ring-substituted derivatives (BPADs) are increasingly used. However, their effects on 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), a pivotal enzyme in glucocorticoid regulation, remain poorly characterized. Here, we evaluated, for the first time, how BPADs modulate 11β-HSD2 inhibition, providing mechanistic insights into their endocrine-disrupting potential. This study evaluated six BPADs, identifying 4-hydroxyphenyl-naphthalene (BPH) as the most potent inhibitor (human IC = 1.26 µM; rat IC = 4.17 µM), with structure-activity relationships (SAR) revealing critical roles for hydrophobicity (LogP) and steric bulk. Enzyme kinetic inhibition analyses demonstrated competitive or mixed-type inhibition of BPADs, and surface plasmon resonance (SPR) confirmed direct binding of BPH to 11β-HSD2. Molecular docking further highlighted key interactions with residues (Asn167, Lys236) in the steroid-binding pocket. Cellular assays in BeWo cells confirmed functional inhibition of endogenous 11β-HSD2. Notably, human 11β-HSD2 exhibited greater sensitivity than rat ortholog towards BPADs, attributed to a Ser92→Thr92 substitution of 11β-HSD2 sequences. These findings positioned BPADs as novel chemical probes for 11β-HSD2 studies and warranted investigation into their endocrine-disrupting potential, particularly in prenatal contexts where placental 11β-HSD2 safeguards fetal development.
Coffee consumption and its association with vitamin D level, lifestyle factors, and mental health symptoms among adults in Saudi Arabia.
Hakim NA
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41418945 · Publisher ↗
Coffee is widely consumed in Saudi Arabia, but its relationship with vitamin D status and related health indicators remains unclear. This cross-sectional study examined associations between coffee consumption, serum 25-h...
Coffee is widely consumed in Saudi Arabia, but its relationship with vitamin D status and related health indicators remains unclear. This cross-sectional study examined associations between coffee consumption, serum 25-hydroxyvitamin D [25(OH)D], lifestyle factors, and mental health symptoms in 387 adults aged 20-60 years recruited in Saudi Arabia (February-March 2024). Participants were classified as normal (≤3 cups/day) or high (>3 cups/day) coffee consumers. Anthropometric measures and serum 25(OH)D and parathyroid hormone were obtained from medical records, and diet, physical activity, sun exposure, and mental health symptoms were assessed by questionnaire. Associations were examined using group comparisons and multivariable regression models. Compared with normal coffee consumers, high coffee consumers had higher BMI (p = 0.043) and lower serum 25(OH)D (p = 0.05). In multivariable linear regression, higher caffeine intake was associated with lower serum 25(OH)D (β = -0.04 nmol/L per mg/day; 95 % CI -0.055 to -0.027; p < 0.001). In logistic regression, higher caffeine intake was associated with lower odds of vitamin D deficiency (<30 nmol/L) (OR = 0.98 per mg/day; 95 % CI 0.97-0.99; p < 0.001). High coffee consumers more frequently reported sleep disturbance/insomnia (49.1 % vs 34.2 %), sweating (20.8 % vs 9.6 %), and raised heart rate (27.7 % vs 17.2 %) (all p < 0.01), whereas headache, irritability, anxiety, and depression did not differ between groups. In this sample of Saudi adults, higher coffee intake was associated with lower 25(OH)D, higher BMI, and more arousal-related symptoms. These observational findings warrant confirmation in longitudinal or interventional studies to clarify temporality and inform public health strategies.
Vitamin D levels in SARS-CoV-2: Do current adequacy thresholds reflect clinical risk? Insights from a large Turkish cohort.
Dandinoğlu T, Akselim S
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41412222 · Publisher ↗
The clinical relevance of serum 25-hydroxyvitamin D [25(OH)D] concentrations in SARS-CoV-2 infection remains uncertain. Most thresholds used to define adequacy were developed for skeletal outcomes, and it is unclear whet...
The clinical relevance of serum 25-hydroxyvitamin D [25(OH)D] concentrations in SARS-CoV-2 infection remains uncertain. Most thresholds used to define adequacy were developed for skeletal outcomes, and it is unclear whether they reflect immunerelated risk. To examine whether serum 25(OH)D levels are associated with disease severity, inflammatory and biochemical markers, or clinical outcomes, we conducted a retrospective cohort analysis including 1136 hospitalized patients with PCR-confirmed SARS-CoV-2 infection. Clinical severity at admission, oxygen requirement, intensive care unit transfer, invasive ventilation, inflammatory markers, length of hospital stay, and in-hospital mortality were compared across vitamin D groups. No significant associations were observed between serum 25(OH)D levels and clinical or laboratory findings. Correlation analyses likewise did not reveal meaningful relationships with inflammatory parameters. In this large hospitalized cohort with predominantly low serum 25(OH)D concentrations, we found no evidence that vitamin D status influenced COVID-19 severity or outcomes. These results indicate that commonly applied adequacy thresholds, including lower immune-related levels, may not provide useful risk stratification in hospitalized patients with COVID-19.
Cholecystokinin (CCK) mediates CCKBR to regulate androgen secretion via the steroid pathway in Bactrian camel Sertoli cells.
Wang Q, Wang W, Nan J … +2 more , Zhang Y, Zhao X
J Steroid Biochem Mol Biol · 2026 Mar · PMID 41411793 · Publisher ↗
This study aimed to identify differentially expressed genes (DEGs) in the testes of Bactrian camels during estrus and anestrus and investigate the regulatory role of cholecystokinin (CCK) and its receptor (CCKBR) in andr...
This study aimed to identify differentially expressed genes (DEGs) in the testes of Bactrian camels during estrus and anestrus and investigate the regulatory role of cholecystokinin (CCK) and its receptor (CCKBR) in androgen synthesis. RNA sequencing was performed on six testicular samples (estrus, n = 3; anestrus, n = 3). A total of 291 DEGs were identified, including 27 upregulated and 264 downregulated in estrus. Gene Ontology (GO) enrichment analysis revealed that CCKBR was significantly enriched in reproduction-related pathways, and STRING analysis showed a close association between CCK and CCKBR. Further qRT-PCR, Western blot, and immunofluorescence (IF) analyses demonstrated significantly higher mRNA and protein levels of CCK/CCKBR in estrus testes (P < 0.01), with both localized in Sertoli cells, Leydig cells, primary spermatocytes, and spermatogonia. Primary Sertoli cells, confirmed by WT1 co-localization, were transfected with p-IRES2-EGFP-CCK and siRNA-CCK. Results showed that CCK overexpression significantly reduced testosterone (T) and dihydrotestosterone (DHT) levels (P < 0.05), while upregulating androgen receptor (AR) and key androgen synthesis enzymes (StAR, P450scc, 3β-HSD) (P < 0.05 or P < 0.01). In contrast, siRNA-CCK exerted the opposite effects. In conclusion, our study highlights the CCK/CCKBR axis as a crucial regulator of seasonal testicular function in Bactrian camels, with CCK negatively regulating testicular androgen synthesis by modulating AR and androgen synthesis enzymes. These findings provide valuable insights into the reproductive biology of Bactrian camels and offer a novel pathway for understanding seasonal fertility regulation in male mammals. This has important implications for enhancing camel breeding efficiency and supporting conservation efforts.
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