Journal of Steroid Biochemistry and Molecular Biology最新文献

Bis(monoacylglycero)phosphate protects murine RAW 264.7 macrophages against 7-Ketocholesterol-induced apoptosis and impaired autophagy 磷酸二酯（单酰基甘油）可保护小鼠RAW 264.7巨噬细胞免受7-酮胆固醇诱导的凋亡和受损的自噬。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-05-01 Epub Date: 2026-02-10 DOI: 10.1016/j.jsbmb.2026.106955

Remi Lambert , Sherine Montillet , Clara Hennot , Agathe Diaz-Gonzalez , Marion Guichard , Emeline Cros-Perrial , Lars Petter Jordheim , Karen Gaget , Federica Calevro , Celine Luquain-Costaz , Isabelle Delton

Atherosclerosis, a leading cause of cardiovascular disease, is driven by the accumulation of oxidized low-density lipoproteins (oxLDL) in arterial walls. 7-Ketocholesterol (7KC), a major oxysterol found in oxLDL and atherosclerotic plaques, triggers multiple cell injuries including loss of lysosomal integrity, oxidative stress, apoptosis, and impaired autophagy in vascular cells. Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid, is a unique phospholipid concentrated in the endolysosomal compartment, known to regulate vesicle dynamics, lysosomal enzyme activities, intracellular cholesterol trafficking and its oxidative metabolism. Using a validated model of BMP enrichment in murine RAW 264.7 macrophages, we investigated whether BMP could exert protective activity against 7KC-induced damage. Our findings revealed that BMP enrichment provides comprehensive protection against 7KC at the cellular level by preserving cell viability, morphology, and neutral lipid balance. Mechanistically, BMP enrichment prevented apoptosis by maintaining mitochondrial integrity and blocking caspase activation. This was demonstrated by normalized BAX/BCL2 ratios, preserved pro-Caspase-3 levels, and reduced PARP cleavage. Remarkably, BMP enrichment also restored autophagic flux, thereby preventing the pathological accumulation of LC3-II and p62 that characterizes autophagy dysfunction. Enhanced colocalization between LC3 and BMP suggests direct functional interactions in the stress response. Gene expression analysis confirmed that BMP enrichment normalized the transcriptional dysregulation of key autophagy regulators, including Sqstm1, Becn1, and Pink1. Taken together, these results suggest that BMP is an endogenous protective factor that counteracts 7KC-induced cellular damage at multiple steps by regulating cell death and autophagy pathways in a coordinated manner.

动脉粥样硬化是心血管疾病的主要原因，是由动脉壁中氧化低密度脂蛋白（oxLDL）的积累所驱动的。7-酮胆固醇（7KC）是在oxLDL和动脉粥样硬化斑块中发现的一种主要的氧固醇，可引发多种细胞损伤，包括溶酶体完整性丧失、氧化应激、细胞凋亡和血管细胞自噬受损。双（单酰基甘油）磷酸（BMP），也被称为溶双磷脂酸，是一种独特的磷脂，集中在内溶酶体腔室中，已知调节囊泡动力学，溶酶体酶活性，细胞内胆固醇运输及其氧化代谢。通过验证BMP在小鼠RAW 264.7巨噬细胞中富集的模型，我们研究了BMP是否对7kc诱导的损伤发挥保护作用。我们的研究结果表明，BMP富集在细胞水平上通过保持细胞活力、形态和中性脂质平衡，对7KC提供全面的保护。从机制上讲，BMP富集通过维持线粒体完整性和阻断caspase激活来阻止细胞凋亡。这可以通过正常化的BAX/BCL2比率、保留的caspase -3亲水平和减少的PARP切割来证明。值得注意的是，BMP富集也恢复了自噬通量，从而阻止了LC3-II和p62的病理积累，而LC3-II和p62是自噬功能障碍的特征。LC3和BMP之间的共定位增强表明在应激反应中有直接的功能相互作用。基因表达分析证实，BMP富集使包括Sqstm1、Becn1和Pink1在内的关键自噬调节因子的转录失调正常化。综上所述，这些结果表明BMP是一种内源性保护因子，通过协调调节细胞死亡和自噬途径，在多个步骤中抵消7kc诱导的细胞损伤。

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引用次数: 0

Fenchone alleviates 7-ketocholesterol-induced oxiapoptophagy through activation of KLF4-PPARγ-Arg1-mediated M2 macrophage signalling 芬可酮通过激活klf4 - ppar γ- arg1介导的M2巨噬细胞信号通路，减轻7-酮胆固醇诱导的氧化细胞吞噬。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-05-01 Epub Date: 2026-02-04 DOI: 10.1016/j.jsbmb.2026.106951

Sangeetha Ravi , Livya Catherene Martin , Manikandan Kumaresan , Jaya Suriya Mani , Beulaja Manikandan , Manikandan Ramar

7-ketocholesterol (7KCh), a cytotoxic oxysterol enriched in atherosclerotic plaques, provokes macrophage dysfunction through oxiapoptophagy, a linked process of oxidative stress, apoptosis and autophagy culminating in pro-inflammatory M1 polarization. Targeting this process could mitigate oxysterol-driven vascular inflammation. In this study, murine IC-21 macrophages were induced with 7KCh and co-exposed to fenchone, a bicyclic monoterpene with known anti-inflammatory properties. Cellular oxidative stress, apoptosis and autophagy were assessed by spectrofluorometric and cytometric assays. Expression of key mediators (iNOS, COX2, HO1, Casp3, Bcl2, LC3B, PARP1, Arg1, KLF4 and PPARγ) was quantified by RT-qPCR and western blotting. Molecular docking was used to identify interactions of fenchone with KLF4 and PPARγ. The results showed that 7KCh significantly increased ROS and NO production, disrupted mitochondrial membrane potential and induced apoptosis and autophagy in macrophages. Fenchone co-treatment counteracted these effects, restoring redox balance and membrane integrity. Molecular analyses revealed downregulation of iNOS, COX2, Casp3 and PARP1, alongside upregulation of HO1, Arg1, KLF4 and PPARγ. Docking analysis confirmed strong binding of fenchone to KLF4 and PPARγ, suggesting transcriptional regulation of macrophage polarization via the KLF4-PPARγ-Arg1 axis. These findings suggest that fenchone mitigates 7KCh-induced oxiapoptophagy and reprograms macrophages toward an anti-inflammatory M2 phenotype through modulation of KLF4/PPARγ signalling, positioning fenchone as a potential immunomodulatory candidate for combating oxysterol-mediated vascular inflammation.

7-酮胆固醇（7KCh）是一种富含动脉粥样硬化斑块的细胞毒性氧固醇，通过氧化应激、细胞凋亡和自噬的相关过程引起巨噬细胞功能障碍，最终导致促炎M1极化。以这一过程为靶点可以减轻由氧甾醇引起的血管炎症。在这项研究中，用7KCh诱导小鼠IC-21巨噬细胞，并共同暴露于芬屈酮，一种已知具有抗炎特性的双环单萜。细胞氧化应激、细胞凋亡和自噬通过荧光光谱和细胞计数测定。RT-qPCR和western blotting检测关键介质（iNOS、COX2、HO1、Casp3、Bcl2、LC3B、PARP1、Arg1、KLF4和PPARγ）的表达。利用分子对接技术鉴定了fenchone与KLF4和PPARγ的相互作用。结果表明，7KCh显著增加巨噬细胞ROS和NO的生成，破坏线粒体膜电位，诱导巨噬细胞凋亡和自噬。Fenchone共处理抵消了这些影响，恢复氧化还原平衡和膜完整性。分子分析显示iNOS、COX2、Casp3和PARP1下调，HO1、Arg1、KLF4和PPARγ上调。对接分析证实了fenchone与KLF4和PPARγ的强结合，提示通过KLF4-PPARγ- arg1轴对巨噬细胞极化进行转录调控。这些发现表明，鸣酮可以通过调节KLF4/PPARγ信号传导，减轻7kch诱导的氧化细胞吞噬，并将巨噬细胞重编码为抗炎的M2表型，从而将鸣酮定位为对抗氧甾醇介导的血管炎症的潜在免疫调节候选物。

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引用次数: 0

What can we learn from the history of steroid metabolites and the ongoing identification of novel biologically active steroid metabolites? 我们可以从类固醇代谢物的历史和正在进行的新的生物活性类固醇代谢物的鉴定中学到什么？

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-05-01 Epub Date: 2026-02-10 DOI: 10.1016/j.jsbmb.2026.106954

Alex Odermatt , David J. Morris

Historically, it was thought that primary steroids released from endocrine glands exert their hormonal effects through corresponding receptors in peripheral tissues, and that their metabolism then inactivates them, followed by excretion. However, the metabolism of primary steroids is not just a way of inactivating and excreting them, but generates a variety of metabolites with different biological properties. In this review, we outline how various active steroid metabolites were discovered, describe some of the ways they are generated, and how they can in a non-classical way act on receptors or alter the activity of steroid metabolizing enzymes, thereby indirectly affecting receptor activities. Examples include the 5α-reduced ring-A metabolites of 11-deoxycorticosterone (DOC) and progesterone that are formed in the brain, act as neurosteroids and exert effects through the GABA-A membrane receptor. Another example is 11-ketoprogesterone that potently activates mineralocorticoid receptors (MR), but not glucocorticoid receptors (GR), and is more potent than its 11β-hydroxylated form, in contrast to glucocorticoids. Moreover, we discuss the microbiome as important source of bioactive metabolites, exemplified by the 11β-hydroxylated 5α-reduced ring-A corticosteroid and progesterone metabolites that were shown as potent 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) inhibitors. 11β-HSD2 inhibition results in cortisol-induced MR activation, sodium retention and hypertension. Furthermore, microbial 17,20-desmolase activity can convert glucocorticoids to androgens, potentially influencing diseases and therapeutic outcomes. There are still many knowledge gaps regarding bioactive steroid metabolites. Identifying additional bioactive steroid metabolites and characterizing their genomic and non-genomic effects should help uncovering their cell-specific functions and contributions to the maintenance of homeostatic regulation.

从历史上看，人们认为内分泌腺释放的初级类固醇通过外周组织中相应的受体发挥激素作用，然后通过代谢使其失活，然后排泄。然而，原代类固醇的代谢不仅仅是使其失活和排泄，而是产生多种具有不同生物学特性的代谢物。在这篇综述中，我们概述了各种活性类固醇代谢物是如何被发现的，描述了它们产生的一些方式，以及它们如何以非经典的方式作用于受体或改变类固醇代谢酶的活性，从而间接影响受体的活性。例如，在大脑中形成的11-脱氧皮质酮（DOC）和孕酮的5α-还原环a代谢物，作为神经类固醇，通过GABA-A膜受体发挥作用。另一个例子是11-酮孕酮，它能有效激活矿皮质激素受体（MR），但不能激活糖皮质激素受体（GR），与糖皮质激素相比，它比11β-羟基化形式更有效。此外，我们还讨论了微生物组作为生物活性代谢物的重要来源，例如11β-羟基化5α-还原环a皮质类固醇和孕酮代谢物被证明是有效的11β-羟基类固醇脱氢酶2 （11β-HSD2）抑制剂。11β-HSD2抑制可导致皮质醇诱导的MR激活、钠潴留和高血压。此外，微生物17,20-去糖化酶活性可以将糖皮质激素转化为雄激素，潜在地影响疾病和治疗结果。关于生物活性类固醇代谢物仍有许多知识空白。鉴定其他生物活性类固醇代谢物并描述其基因组和非基因组效应将有助于揭示其细胞特异性功能和对维持体内平衡调节的贡献。

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引用次数: 0

Interleukin-2 receptor γ blocks the development of Leydig cells from stem/progenitor cells in male rats via JAK1-STAT3 pathway and GSDMD-mediated pyroptosis 白细胞介素-2受体γ通过JAK1-STAT3通路和gsdmd介导的焦亡，阻断雄性大鼠干细胞/祖细胞间质细胞的发育。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-05-01 Epub Date: 2026-02-07 DOI: 10.1016/j.jsbmb.2026.106953

Jingyi Zheng , Qingyuan Wang , Huiqian Zhang , Yubin Xu , Feilu Wang , Yiyan Wang , Xiaoheng Li , Ren-Shan Ge

Interleukin-2 (IL-2) receptor γ (IL2RG) is present in the Leydig cell lineage, but its functional role remains elusive. To investigate how IL2RG impacts Leydig cell development from stem cells and elucidate the underlying mechanisms, we used a rat model of ethane dimethanesulfonate (EDS)-induced cell depletion in Wild-type (WT) and Il2rg knockout (KO) mice. WT and KO male rats received intratesticular IL-2 injections (1 and 10 ng/testis) from day 7 to day 21 post-EDS. Stem Leydig cells around tubules and isolated progenitor Leydig cells were cultured with IL-2 (1 and 10 ng/mL) with/without STAT3 inhibitor. Hormone levels, cell counts, gene/protein expression, and signaling pathways were analyzed. The results revealed that IL-2 significantly reduced serum testosterone levels in WT rats but had no effects in KO rats, without altering luteinizing hormone and follicle-stimulating hormone levels. Furthermore, IL-2 lowered Leydig cell numbers and the labeling index of PCNA in CYP11A1⁺ Leydig cells at 10 ng/testis, and downregulated the expression of SCARB1, HSD3B1, CYP17A1, SRD5A1, and NR5A1, as well as their corresponding mRNA levels in WT rats with no effect observed in KO rats. IL-2 also inhibited the incorporation of 5-ethynyl-2′-deoxyuridine (EdU) into stem Leydig cells in WT rats and [³H] thymidine incorporation into progenitor Leydig cells, as well as their differentiation. Importantly, the effects of IL-2 were reversed by the STAT3 inhibitor. Signaling pathway analysis showed that IL-2 exerted effects via increasing JAK1, STAT5, and STAT3 phosphorylation. This study provides insights into the inhibitory effects of IL2RG on Leydig cell development and highlights the involvement of the JAK-STAT pathway, offering potential targets for further exploration in the context of Leydig cell biology and male reproductive health.

白细胞介素-2 （IL-2）受体γ (IL2RG)存在于间质细胞系中，但其功能作用尚不明确。为了研究IL2RG如何影响干细胞的间质细胞发育并阐明其潜在机制，我们在野生型（WT）和IL2RG敲除（KO）小鼠中使用乙烷二甲基磺酸（EDS）诱导的细胞衰竭大鼠模型。WT和KO雄性大鼠在eds后第7天至第21天接受睾丸内注射IL-2（1和10ng/睾丸）。用含/不含STAT3抑制剂的IL-2（1和10ng/mL）培养小管周围的间质干细胞和分离的前间质细胞。分析激素水平、细胞计数、基因/蛋白表达和信号通路。结果显示，IL-2显著降低了WT大鼠的血清睾酮水平，但对KO大鼠没有影响，没有改变黄体生成素和促卵泡激素水平。此外，IL-2在10ng/睾丸时可降低WT大鼠间质间质细胞数量和CYP11A1+间质间质细胞PCNA标记指数，下调SCARB1、HSD3B1、CYP17A1、SRD5A1和NR5A1的表达及其相应mRNA水平，而在KO大鼠中未见影响。IL-2还能抑制WT大鼠间质干细胞中5-乙基-2′-脱氧尿苷（EdU）的掺入和[3H]胸苷向前间质细胞中的掺入及其分化。重要的是，STAT3抑制剂逆转了IL-2的作用。信号通路分析表明，IL-2通过增加JAK1、STAT5和STAT3磷酸化发挥作用。本研究揭示了IL2RG对间质细胞发育的抑制作用，并强调了JAK-STAT通路的参与，为间质细胞生物学和男性生殖健康的进一步探索提供了潜在的靶点。

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引用次数: 0

Integrative metabolomics and network pharmacology reveal the therapeutic mechanisms of Inonotus hispidus (Bull.) P. Karst. extract against primary dysmenorrhea 综合代谢组学和网络药理学揭示了Inonotus hispidus的治疗机制。p .岩溶。治疗原发性痛经。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-05-01 Epub Date: 2026-02-10 DOI: 10.1016/j.jsbmb.2026.106957

Qingchun Wang , Haiying Bao , Jingjing Zhao , Hailong Liang

Primary dysmenorrhea (PD) is a common gynecological disorder characterized by uterine hypercontraction and inflammation. This study employed an integrated strategy combining serum metabolomics, network pharmacology, and experimental validation to investigate the therapeutic potential of different extracts of Inonotus hispidus. In a rat PD model induced by estradiol benzoate and oxytocin, petroleum ether extracts of I. hispidus (MP) significantly alleviated writhing responses, attenuated uterine tissue injury, and corrected key biochemical imbalances, including the pivotal PGF₂α/PGE₂ ratio and levels of inflammatory cytokines (TNF-α, IL-6, IL-1β). Serum metabolomics analysis revealed that the therapeutic effect of MP was fundamentally linked to the systemic rectification of dysregulated arachidonic acid (AA) metabolism. Network pharmacology and subsequent experimental validation identified that MP concurrently modulates several interconnected signaling pathways. Crucially, MP activated PPARγ by promoting its dephosphorylation, which in turn potently suppressed the NLRP3 inflammasome. Concurrently, it regulated the PI3K/Akt/NF-κB survival-inflammatory axis and inhibited the RhoA/ROCK-mediated contractile pathway, reducing phosphorylation of downstream effectors MYPT1 and MLC. In vitro, the medicated serum (MP-S), containing systemically absorbed bioactive compounds, demonstrated superior and more comprehensive cytoprotection against oxytocin-induced oxidative stress, mitochondrial dysfunction, and apoptosis in rat uterine smooth muscle cells (RUSMCs) than the single compound ergosterone, underscoring the principle of multi-component synergy. Collectively, this work delineates a multi-target mechanism for MP against PD, involving the correction of AA metabolic dysregulation, activation of the PPARγ-NLRP3 axis to suppress inflammation, and inhibition of pathways driving smooth muscle hypercontraction, providing a solid scientific foundation for its development as a modern, multi-targeted therapeutic agent.

原发性痛经（PD）是一种常见的妇科疾病，其特征是子宫过度收缩和炎症。本研究采用血清代谢组学、网络药理学和实验验证相结合的综合策略，探讨了褐皮草不同提取物的治疗潜力。在雌二醇苯甲酸酯和催产素诱导的大鼠PD模型中，海鞘油醚提取物（MP）显著缓解了扭动反应，减轻了子宫组织损伤，并纠正了关键的生化失衡，包括关键的PGF2α/PGE2比值和炎症因子（TNF-α, IL-6, IL-1β）水平。血清代谢组学分析显示，MP的治疗效果与系统性纠正失调的花生四烯酸（AA）代谢有关。网络药理学和随后的实验验证发现，MP同时调节几个相互关联的信号通路。至关重要的是，MP通过促进PPARγ的去磷酸化来激活PPARγ，这反过来又有效地抑制NLRP3炎症小体。同时，它调节PI3K/Akt/NF-κB存活-炎症轴，抑制RhoA/ rock介导的收缩通路，降低下游效应物MYPT1和MLC的磷酸化。在体外实验中，含有系统吸收生物活性化合物的给药血清（MP-S）在抗催产素诱导的氧化应激、线粒体功能障碍和大鼠子宫平滑肌细胞（RUSMCs）凋亡方面表现出比单一化合物麦角酮更优越、更全面的细胞保护作用，强调了多组分协同作用的原理。总的来说，本研究描绘了MP抗PD的多靶点机制，包括纠正AA代谢失调，激活PPARγ-NLRP3轴抑制炎症，抑制平滑肌过度收缩的途径，为其作为现代多靶点治疗剂的发展提供了坚实的科学基础。

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引用次数: 0

E3 ubiquitin ligase PELI1 promotes ferroptosis in granulosa cells in PCOS by degrading Fth1 E3泛素连接酶Peli1通过降解Fth1促进PCOS颗粒细胞铁凋亡。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-05-01 Epub Date: 2026-01-29 DOI: 10.1016/j.jsbmb.2026.106948

Xiaomeng Zha , Liang Chen , Zhaoping Tan , Tiancheng Wu , Qiaohua Xiong , Haihua Wang , Yuanyuan Kuang , Fei Xing , Aihua Lu , Lili Sun , Yuanzhen Zhang

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.

多囊卵巢综合征（PCOS）是育龄妇女常见的生殖内分泌疾病，以高雄激素血症和排卵障碍为特征。然而，多囊卵巢综合征卵巢异常的潜在机制仍有待研究。在这项研究中，我们首先通过筛选基于网络的数据库确定了PCOS人群卵巢铁下垂水平的改变。进一步，我们建立了暴露于praster酮的PCOS小鼠模型和颗粒细胞模型，以证实高雄激素可导致卵巢颗粒细胞发生铁下垂。通过转录组测序和细胞实验探讨可能的机制。结果发现，在暴露于prasterone的颗粒细胞中，泛素化通路和P53通路显著富集。E3泛素连接酶PELI1基因在PCOS卵巢中显著高表达，可能通过降解FTH1参与铁下垂。此外，P53基因的高表达与PELI1/FTH1的改变有关。本研究证实高雄激素可通过P53/PELI1/FTH1通路介导卵巢铁下垂的发生，E3泛素连接酶PELI1在其中发挥重要的调控作用。体内，铁死亡抑制剂甲磺酸去铁胺可减轻PCOS小鼠卵巢铁下垂和卵泡发育障碍。本研究为PCOS卵巢病理变化提供了新的认识，并为PCOS的治疗提供了可能的干预措施。

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引用次数: 0

Exploring the feature prioritization and data sampling of PCOS diagnosis via densely connected attention based squeeze deep learning detection model 基于密集连接注意的挤压深度学习检测模型在PCOS诊断中的特征优先化和数据采样研究。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-04-01 Epub Date: 2025-12-31 DOI: 10.1016/j.jsbmb.2025.106933

Siji Jose Pulluparambil , Subrahmanya Bhat

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.

由于多囊卵巢综合征（PCOS）症状的复杂性和现有数据集的数据不平衡问题，准确和及时的诊断仍然是一个挑战。本研究旨在开发一个强大的PCOS检测模型，通过在处理数据平衡问题时引入一种具有有效特征优先级的新型混合方法来解决这些挑战。研究包括预处理、特征选择和PCOS检测三个主要阶段。在预处理阶段，通过结合合成少数派过采样技术（SMOTE）和编辑近邻（ENN）来强调数据集平衡。在此阶段，通过替换空值、平衡数据集和删除不必要的列来提高PCOS检测精度。第二阶段是特征选择，提出了一种独特的混合仿生策略，即大猩猩Salp蜂群模型（GS2TM），以选择最优的优势特征集。GS2TM算法将特征集减少了51.1%，仅保留了23个特征，同时达到了98.7%的最先进精度。此外，针对PCOS的预测，提出了一种多层前馈调整的基于密集连接注意力的挤压卷积检测模型（DASCD）。这项工作的新颖之处在于，统一的管道同时解决了PCOS检测中的三大挑战，即数据集不平衡（SMOTE-ENN）、特征冗余（GS2TM）和过拟合（DASCD with attention），提供了高精度和增强的可解释性。因此，与其他现有的基于ml的检测策略相比，所提出的检测模型大大提高了准确性。具体而言，通过利用GS2TM的23个特征，该模型在PCOS和非PCOS分类方面的准确率达到98.7%。

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引用次数: 0

Androgen production in adrenocortical H295R cells is regulated by thyroid hormone T3 without reciprocal thyroid axis modulation in pediatric CAH 在儿童CAH中，肾上腺皮质H295R细胞的雄激素分泌受甲状腺激素T3的调节，而甲状腺轴没有相互调节

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-04-01 Epub Date: 2026-01-14 DOI: 10.1016/j.jsbmb.2026.106939

Philipp Augsburger , Therina du Toit , Emre Murat Altinkiliç , Sabine Hannema , Christiaan de Bruin , Evangelia Charmandari , Erica L.T. van den Akker , Christa E. Flück

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.

甲状腺激素（THs）是人类发育、细胞分化和代谢的关键调节因子。虽然它们对全身的影响已经确定，但它们在肾上腺雄激素产生中的作用仍不明确。此外，肾上腺雄激素对下丘脑-垂体-甲状腺（HPT）轴的潜在反馈调节尚未得到充分研究。本研究旨在阐明三萜类化合物对肾上腺雄激素的调节作用，并探讨其在先天性肾上腺增生症（CAH）患者中的潜在反馈机制。在一项体外实验中，用3,3 '，5-三碘- l -甲状腺原氨酸（T3）治疗肾上腺皮质癌H295R细胞可显著降低脱氢表雄酮（DHEA）和硫酸脱氢表雄酮（DHEA -sulfate）的产生，同时适度增加睾酮(T)和雄烯二酮（A4）。这些变化与HSD3B2和AKR1C3的表达增加以及CYP17A1的表达减少有关。转录组学分析还显示，通过T3治疗，与类固醇生成和肾上腺发育相关的途径丰富。在研究的临床部分，分析了儿科CAH患者的激素水平。血清游离甲状腺素（fT4）和促甲状腺激素（TSH）与肾上腺雄激素DHEA和A4呈弱负相关。然而，在控制良好的患者和高雄激素患者之间，fT4或TSH浓度没有差异，这表明肾上腺雄激素在HPT轴上缺乏反馈调节。综上所述，这些发现表明，三萜类化合物通过调节关键类固醇生成酶的活性来调节肾上腺雄激素的产生。这种关系似乎主要是单向的，这影响肾上腺甾体生成，但肾上腺雄激素不改变HPT轴功能。

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引用次数: 0

Targeting cholinesterases with steroid hormone derivatives: Insights from In Vitro assays and molecular modeling 靶向胆碱酯酶与类固醇激素衍生物：从体外分析和分子模型的见解。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-04-01 Epub Date: 2026-01-31 DOI: 10.1016/j.jsbmb.2026.106950

Jovana J. Ajduković , Ana Matošević , Anita Bosak , Strahinja Kovačević , Milica Karadžić Banjac , Ivana Z. Kuzminac , Andrea R. Nikolić , Marina P. Savić

Steroids represent a large family of organic compounds that, as signaling molecules, play important role in variety of physiological processes as control of metabolic pathways, inflammation processes, immune response, and growth, development and reproduction. Modifying the steroid core has allowed the creation of novel synthetic derivatives, which can offer significant benefits in medicine for treating a wide range of pathological conditions. Quite a number of natural steroids have been identified as effective inhibitors of cholinesterases, pointing them out as potential therapeutic alternatives in the application in Alzheimer’s disease (AD). Nevertheless, only a limited number of synthetic steroids have so far been studied as cholinesterase inhibitors, highlighting an opportunity for the development of new therapeutic agents derived from natural steroidal frameworks. In this study, we selected a set of structurally diverse steroid hormone derivatives and evaluated in vitro their inhibitory activity against human AChE and BChE. IC₅₀ values were estimated for several of the most active compounds, with pyridine-containing hydroxy derivative 8 exhibiting affinity toward BChE (IC₅₀ 2.76 µM), similar to that for clinically used cholinesterase inhibitors. In silico analyses suggest that hydrophobic interactions with key amino-acid residues predominantly govern the binding of these compounds within the enzyme’s active site.

类固醇是一大类有机化合物，作为信号分子，在多种生理过程中发挥重要作用，如代谢途径、炎症过程、免疫反应、生长、发育和繁殖的控制。修改类固醇核心允许创造新的合成衍生物，这可以提供显著的好处，在医学上治疗广泛的病理条件。相当多的天然类固醇已被确定为有效的胆碱酯酶抑制剂，指出它们在阿尔茨海默病（AD）的应用中具有潜在的治疗选择。然而，到目前为止，只有有限数量的合成类固醇作为胆碱酯酶抑制剂进行了研究，这突出了开发源自天然类固醇框架的新治疗剂的机会。在这项研究中，我们选择了一组结构多样的类固醇激素衍生物，并在体外评估了它们对人AChE和BChE的抑制活性。对几种最具活性的化合物的IC50值进行了估计，其中含吡啶的羟基衍生物8对BChE具有亲和力（IC50为2.76µM），与临床使用的胆碱酯酶抑制剂相似。计算机分析表明，与关键氨基酸残基的疏水相互作用主要控制了酶活性位点内这些化合物的结合。

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引用次数: 0

Anabolic-androgenic steroids at supraphysiological doses: Cardiovascular impacts and pathophysiological mechanisms 超生理剂量的合成代谢雄激素类固醇：心血管影响和病理生理机制

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-04-01 Epub Date: 2026-01-13 DOI: 10.1016/j.jsbmb.2026.106938

Higor Souza Nascimento , Marcella Guerra Corrêa , Odonilton Lima Lemos , Hernando Nascimento Lima , Liliany Souza de Brito Amaral

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.

这篇叙述性综述探讨了非治疗性使用超生理剂量的合成代谢雄激素类固醇（AAS）相关的心血管风险。AAS最初用于治疗性腺功能减退和贫血等临床疾病，但越来越多地被滥用于美容和提高性能，剂量往往远远超过治疗建议。通过对PubMed(2015-2025) 34项研究的文献综述，分析大剂量AAS使用的分子机制和心血管后果。基因组和非基因组途径，以及IGF-1轴的调节，是导致心肌重构、高血压、血脂异常、血栓形成、内皮功能障碍和全身性炎症的基因表达和细胞代谢改变的基础。这些影响因行为因素如多种药物和药物滥用而进一步加剧。尽管超生理剂量的临床试验存在伦理限制，但实验和流行病学数据一致表明，过量使用AAS会显著增加不良心血管事件的风险。这项工作强调了公共卫生政策、教育举措和纵向研究的迫切需要，以评估现实世界的使用模式并减轻与AAS滥用相关的危害。

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引用次数: 0