Journal of Steroid Biochemistry and Molecular Biology最新文献_第8页

Urine sterols metabolomics study during summer training of winter paralympic snowboarders 冬季残奥会单板滑雪运动员夏季训练期间尿液固醇代谢组学研究

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-01-01 Epub Date: 2025-10-23 DOI: 10.1016/j.jsbmb.2025.106878

Shengkang Jin , Junyu Wu, Yuan Zhang, Yunxin Gao, Wanting Shen, Zhenqin Cheng, Yuqing Qi , Xueping Wu , Xinkai Yu , Qun Zuo

This study used targeted metabolomics approach to explore the effects of strength training on sterol metabolism in Paralympic snowboarders. Sixteen national para-snowboard athletes (12 male, 4 female) were assessed during summer strength training phase. Blood and urine samples were collected during adaptation, maximal strength, and rapid strength training phases. We found that serum 25(OH)D levels improved from deficiency to insufficiency after training. Triglyceride and low-density lipoprotein cholesterol (LDL-C) levels decreased significantly after maximal and rapid strength training. Compared to the adaptation stage, 13 and 12 urinary metabolites were identified in male and female athletes, respectively, during the maximal strength phase, while 9 and 8 metabolites showed differences during the rapid strength phase. A total of 13 and 6 differential metabolites were identified in male and female athletes, respectively, when comparing the rapid strength training phase to the maximal strength training phase. Following cycle strength training, the biosynthesis of steroid hormones as well as the metabolic pathways of androgens and estrogens was activated. After the summer strength training period, urinary differential metabolites in male athletes showed a significant association with LDL-C and serum vitamin D levels. In contrast, among female athletes, urinary dihydroprogesterone levels were significantly correlated with 25(OH)D concentrations. In general, strength training improves blood lipids and serum vitamin D levels, with the most pronounced improvement in vitamin D occurring during the maximal strength phase. Steroid hormone biosynthesis, androgen and estrogen metabolic pathways, and metabolism are affected by exercise training, including bile acid metabolism in males.

本研究采用靶向代谢组学方法探讨力量训练对残奥会单板滑雪运动员固醇代谢的影响。对16名国家残疾人单板滑雪运动员（男12名，女4名）进行夏季力量训练。在适应阶段、最大力量训练阶段和快速力量训练阶段采集血样和尿样。我们发现血清25(OH)D水平在训练后从缺乏改善到不足。最大强度和快速力量训练后，甘油三酯和低密度脂蛋白胆固醇（LDL-C）水平显著下降。与适应阶段相比，男性和女性运动员在最大力量阶段分别鉴定出13种和12种尿液代谢物，而在快速力量阶段分别鉴定出9种和8种代谢物。在比较快速力量训练阶段和最大力量训练阶段时，在男性和女性运动员中分别鉴定出13种和6种差异代谢物。循环力量训练后，类固醇激素的生物合成以及雄激素和雌激素的代谢途径被激活。夏季力量训练结束后，男性运动员尿液差异代谢物与LDL-C和血清维生素D水平显著相关。相比之下，在女运动员中，尿二氢孕酮水平与25(OH)D浓度显著相关。一般来说，力量训练可以改善血脂和血清维生素D水平，在最大力量阶段维生素D的改善最为明显。运动训练影响类固醇激素的生物合成、雄激素和雌激素的代谢途径以及代谢，包括男性胆汁酸代谢。

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引用次数: 0

Targeted deletion of Cyp24a1 in the intestine reduces mucosal injury and preserves epithelial proliferation after 5-fluorouracil treatment 在5-氟尿嘧啶治疗后，肠道中Cyp24a1的靶向缺失减少了粘膜损伤并保持了上皮细胞的增殖。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-01-01 Epub Date: 2025-09-05 DOI: 10.1016/j.jsbmb.2025.106857

Phir C.K. Thianhlun , Cyan L. Sylvester , Rebecca K. Sawyer , Hannah R. Wardill , Andrea M. Stringer , Paul H. Anderson

Vitamin D has been proposed to attenuate chemotherapy-induced gastrointestinal mucositis (GM). In the intestine, local catabolism of active vitamin D [1,25-dihydroxyvitamin D₃] is mediated by the enzyme Cyp24a1. This study assessed whether deletion of Cyp24a1 specifically in intestinal epithelial cells can protect against 5-fluorouracil (5-FU)-induced intestinal injury and microbiome disruption in mice. Using the Cre-loxP system, Cyp24a1 was selectively ablated in the intestinal epithelium (IEC-KO mice). Male IEC-KO and Cyp24a1^fl/fl^ littermate control mice received a single intraperitoneal injection of 5-FU (450 mg/kg) or saline and were euthanised 48 h later. In control mice, 5-FU markedly reduced duodenal villous height and crypt area (p < 0.01), whereas IEC-KO mice retained intestinal architecture. Proliferation, measured by Ki-67 immunostaining, was preserved in both the small and large intestine of IEC-KO mice following 5-FU treatment (p < 0.05). Notably, colonic Tlr4 mRNA was significantly upregulated in IEC-KO mice (p < 0.001), with no corresponding increase in inflammatory cytokines. 16S rRNA sequencing revealed no change in overall microbial diversity; however, there were notable differences in the relative abundance of key taxa, such as Bifidobacteriaceae and Alistipes. These findings suggest that intestinal Cyp24a1 contributes to susceptibility to chemotherapy-induced intestinal injury and microbial dysbiosis, and that its deletion enhances epithelial regeneration, potentially via innate immune pathways.

维生素D被认为可以减轻化疗引起的胃肠道黏膜炎（GM）。在肠道中，活性维生素D[1,25-二羟基维生素D₃]的局部分解代谢是由Cyp24a1酶介导的。本研究评估了肠上皮细胞特异性缺失Cyp24a1是否可以保护小鼠免受5-氟尿嘧啶（5-FU）诱导的肠道损伤和微生物组破坏。使用Cre-loxP系统，在肠上皮（IEC-KO小鼠）中选择性消融Cyp24a1。雄性IEC-KO和Cyp24a1^fl/fl^同窝对照小鼠一次性腹腔注射5-FU （450mg/kg）或生理盐水，48小时后安乐死。在对照组小鼠中，5-FU显著降低了十二指肠绒毛高度和隐窝面积（p < 0.01），而IEC-KO小鼠保留了肠道结构。Ki-67免疫染色法检测，5-FU处理后，IEC-KO小鼠小肠和大肠均保持了增殖（p < 0.05）。值得注意的是，在IEC-KO小鼠中，结肠Tlr4 mRNA显著上调（p < 0.001），而炎症细胞因子未相应增加。16S rRNA测序显示总体微生物多样性没有变化；但双歧杆菌科、双歧杆菌科等关键类群的相对丰度存在显著差异。这些发现表明，肠道Cyp24a1对化疗诱导的肠道损伤和微生物生态失调的易感性有贡献，并且它的缺失可能通过先天免疫途径增强上皮再生。

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引用次数: 0

Research progress on the function, expression and enzyme activity regulation of 17β-HSD1 in mammals 哺乳动物17β-HSD1的功能、表达及酶活性调控研究进展

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-01-01 Epub Date: 2025-09-17 DOI: 10.1016/j.jsbmb.2025.106864

Shanshan Chen , Haoyi Feng , Tong Yu, Yizhao Li, Xuelei Han, Xinjian Li, Kejun Wang, Feng Yang

17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) can catalyze the reduction of the less active estrone (E₁) to the more active estradiol (E₂). It has a significant impact on the reproduction of female animals, follicular development, the development of the breasts and reproductive organs in reproductive-age women, as well as the physical health, bones and cardiovascular system of postmenopausal women. This review summarizes the research progress on the expression, biological function, and regulatory mechanisms of 17β-HSD1 in estrogen-dependent diseases, including cancer. It also discusses the role of 17β-HSD1 in female reproduction processes, such as follicle development, and the regulation of its enzyme activity by activin A and insulin-like growth factor 1 (IGF-1). Furthermore, the review explores how phosphorylation at key sites influences its enzyme’s activity, aiming to enhance the understanding of its regulatory mechanisms and improve the clarity of related research findings. This review systematically summarizes the research progress of 17β-HSD1 expression and enzyme activity regulation, which can provide theoretical reference for the development of animal breeding technology and the treatment of estrogen dependent diseases.

17β-羟基类固醇脱氢酶1 （17β-HSD1）可以催化活性较低的雌酮（E1）还原为活性较高的雌二醇（E2）。它对雌性动物的繁殖、卵泡发育、育龄妇女乳房和生殖器官的发育，以及绝经后妇女的身体健康、骨骼和心血管系统都有重大影响。本文就17β-HSD1在雌激素依赖性疾病（包括癌症）中的表达、生物学功能及调控机制的研究进展进行综述。本文还讨论了17β-HSD1在女性生殖过程中的作用，如卵泡发育，以及激活素A和胰岛素样生长因子1 （IGF-1）对其酶活性的调节。此外，本文还探讨了关键位点的磷酸化如何影响其酶的活性，旨在加深对其调控机制的理解，并提高相关研究结果的清晰度。本文系统总结了17β-HSD1表达及酶活性调控的研究进展，可为动物育种技术的发展和雌激素依赖性疾病的治疗提供理论参考。

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引用次数: 0

Corrigendum to “Low-fat diets and testosterone in men: Systematic review and meta-analysis of intervention studies” [Journal of Steroid Biochemistry and Molecular Biology, 210 (2021) 105878] “低脂饮食和男性睾酮：干预研究的系统回顾和荟萃分析”的勘误表[Journal of steroids Biochemistry and Molecular Biology， 210(2021) 105878]。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-01-01 Epub Date: 2025-10-25 DOI: 10.1016/j.jsbmb.2025.106880

Joseph Whittaker , Kexin Wu

引用次数: 0

Bushen Huoxue formula component β-Estradiol 3-acetate treats osteoarthritis through enhancing the TLR4 ubiquitination 补肾活血方成分β-雌二醇3-醋酸酯通过增强TLR4泛素化治疗骨关节炎。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-01-01 Epub Date: 2025-09-12 DOI: 10.1016/j.jsbmb.2025.106862

Xiaoli Liu , Shan Wang , Chuangfu Kuang , Yuwen Deng , Shuaicai Yuan , Juying Zou

We aim to explore the key metabolic components and underlying mechanisms of the Bushen Huoxue Formula (BH) in treating Osteoarthritis (OA). The mouse knee OA model was constructed using the destabilization of the medial meniscus method. OA mice were orally administered the BH. Mouse cartilage damage was assessed. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS), network pharmacology analysis and molecular docking were employed to analyze the serum metabolite components and target protein of BH. After lipopolysaccharide (LPS) treatment, different concentrations of β-Estradiol 3-acetate were added to primary chondrocytes. Flow cytometry was utilized for detecting cell apoptosis. The Ubiquitin-Specific Protease 13 (USP13)/Toll-like Receptor 4 (TLR4)/Myeloid Differentiation Primary Response Protein 88 (MYD88)/NF-κB pathway and the TLR4 ubiquitination levels were assessed using immunological quantification and biochemical methods. Relative to normal mice, OA mice exhibited decreased knee joint cartilage thickness and increased inflammatory damage. BH treatment reversed these effects. Furthermore, BH enhanced TLR4 ubiquitination. Estradiol acetate was identified as the metabolic component of BH that alleviates OA. Estradiol acetate and its subtype molecule β-Estradiol 3-acetate could bind to the USP13 protein. The β-Estradiol 3-acetate concentration-dependently decreased the elevated levels of USP13, TLR4, MYD88, p-p65/p65 in chondrocytes induced by LPS, while increasing the TLR4 ubiquitination. β-Estradiol 3-acetate reversed LPS-induced chondrocyte apoptosis and elevation of inflammatory factors. Moreover, USP13 overexpression abolished the protective effects of BH and β-Estradiol 3-acetate against LPS-induced chondrocytes. In Conclusion, the BH metabolite β-Estradiol 3-acetate promotes TLR4 ubiquitination to relieve inflammation and apoptosis in OA chondrocytes by inhibiting USP13.

我们旨在探讨补肾活血方治疗骨关节炎（OA）的关键代谢成分及其作用机制。采用内侧半月板失稳法建立小鼠膝关节OA模型。OA小鼠口服BH。评估小鼠软骨损伤。采用高效液相色谱-串联质谱法（HPLC-MS）、网络药理学分析、分子对接等方法对白芍血清代谢物成分和靶蛋白进行分析。脂多糖（LPS）处理后，在原代软骨细胞中加入不同浓度的β-雌二醇3-乙酸酯。流式细胞术检测细胞凋亡。采用免疫定量和生化方法评估泛素特异性蛋白酶13 (USP13)/ toll样受体4 (TLR4)/髓样分化初级反应蛋白88 (MYD88)/NF-κB通路和TLR4泛素化水平。与正常小鼠相比，OA小鼠表现出膝关节软骨厚度减少和炎症损伤增加。BH治疗逆转了这些效果。此外，BH增强了TLR4的泛素化。经鉴定，醋酸雌二醇是BH减轻OA的代谢成分。Estradiol acetate及其亚型分子β-Estradiol 3-acetate可与USP13蛋白结合。β-雌二醇3-醋酸酯浓度依赖性地降低了LPS诱导的软骨细胞中USP13、TLR4、MYD88、p-p65/p65的升高水平，同时增加了TLR4的泛素化。β-雌二醇3-醋酸酯逆转lps诱导的软骨细胞凋亡和炎症因子升高。此外，USP13过表达消除了BH和β-雌二醇3-醋酸酯对lps诱导的软骨细胞的保护作用。综上所述，BH代谢产物β-Estradiol 3-acetate通过抑制USP13，促进TLR4泛素化，减轻OA软骨细胞炎症和凋亡。

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引用次数: 0

17β-estradiol (E2) increases ciliary beat frequency via membrane estrogen receptor β 17β-雌二醇（E2）通过膜雌激素受体β增加纤毛搏动频率。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-01-01 Epub Date: 2025-09-29 DOI: 10.1016/j.jsbmb.2025.106871

Kouta Noriyama , Nobuhisa Todo , Nobuyo Tamiya , Masaki Shigeta , Yuki Toda , Shigekuni Hosogi , Eishi Ashihara

Estrogen receptors (ER) are expressed in various tissues, including the lungs and other respiratory tissues, independent of sex. However, the role of estrogen in the respiratory tract is not fully understood. Airway ciliated cells are important for mucociliary clearance (MCC), which protects the human airways from foreign substances, and ciliary beat frequency (CBF) is an important indicator of MCC efficiency. Although the function of estrogen in airway smooth muscle cells and goblet cells has been studied, its effects on airway ciliated cells remain unclear. Here, we investigated the effect of 17β-estradiol (E2) on CBF. E2 increased CBF and intracellular cAMP concentration ([cAMP]_i) in murine airway ciliated cells, whereas it had no effect on intracellular Ca^2 + concentration and intracellular pH. The selective ERβ inhibitor PHTPP suppressed the E2-induced increase in CBF and [cAMP]_i. β-Estradiol 6-(O-carboxymethyl)oxime: bovine serum albumin conjugate, which activates membrane ER, also increased CBF and [cAMP]_i in murine airway ciliated cells, and PHTPP suppressed these effects. The results of this study indicate that E2 increases CBF by increasing [cAMP]_i via membrane ERβ in murine airway ciliated cells. These results provide new insight into the function of estrogen in airway ciliated cells.

雌激素受体（ER）在各种组织中表达，包括肺和其他呼吸组织，与性别无关。然而，雌激素在呼吸道中的作用尚不完全清楚。气道纤毛细胞在粘膜纤毛清除（mucociliary clearance， MCC）中起着重要的作用，而纤毛搏动频率（ciliary beat frequency， CBF）是MCC效率的重要指标。虽然雌激素在气道平滑肌细胞和杯状细胞中的作用已被研究，但其对气道纤毛细胞的影响尚不清楚。在这里，我们研究了17β-雌二醇（E2）对CBF的影响。E2增加小鼠气道纤毛细胞的CBF和细胞内cAMP浓度（[cAMP]i），而对细胞内Ca2+浓度和细胞内ph没有影响。选择性ERβ抑制剂PHTPP抑制E2诱导的CBF和[cAMP]i的增加。β-雌二醇6-（o -羧甲基）肟：牛血清白蛋白偶联物，激活膜内质网，也增加小鼠气道纤毛细胞的CBF和[cAMP]i，而PHTPP抑制了这些作用。本研究结果表明，E2通过小鼠气道纤毛细胞膜ERβ增加[cAMP]i，从而增加CBF。这些结果为雌激素在气道纤毛细胞中的作用提供了新的认识。

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引用次数: 0

Excess aldosterone and cortisol promote myocardial iron deficiency: A potential pathway to cardiac injury 过量的醛固酮和皮质醇促进心肌铁缺乏：心脏损伤的潜在途径

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-01-01 Epub Date: 2025-10-25 DOI: 10.1016/j.jsbmb.2025.106882

Aleksandar Cirovic

Mineralocorticoid receptor antagonists (MRAs) such as finerenone have shown clinical benefits in heart failure, yet their full mechanisms remain unclear. Recent evidence suggests a novel role of aldosterone in disrupting myocardial iron homeostasis. Aldosterone, via mineralocorticoid receptor (MR) activation, downregulates key iron transporters like transferrin receptor 1 (TfR1) through SGK1 signaling, contributing to myocardial iron deficiency (MID). Cortisol, which circulates at much higher levels than aldosterone and shares similar MR affinity, may similarly promote MID—especially in tissues like the heart where 11β-HSD2 activity is low. Iron deficiency in cardiomyocytes impairs mitochondrial function, reduces ATP synthesis, and promotes fibrosis and inflammation. MRAs may counteract these effects by restoring iron uptake and improving myocardial energetics. This emerging aldosterone–iron axis offers novel insight into the cardiac effects of MR activation and identifies iron homeostasis as a potential therapeutic target. Further research is warranted to explore MRA-mediated modulation of myocardial iron metabolism.

矿皮质激素受体拮抗剂（MRAs）如细烯酮已显示出心力衰竭的临床益处，但其完整机制尚不清楚。最近的证据表明，醛固酮在破坏心肌铁稳态中的新作用。醛固酮通过矿化皮质激素受体（MR）激活，通过SGK1信号下调转铁蛋白受体1 （TfR1）等关键铁转运蛋白，导致心肌铁缺乏（MID）。皮质醇的循环水平比醛固酮高得多，并具有相似的MR亲和力，可能同样促进mid - - -特别是在心脏等11β-HSD2活性较低的组织中。心肌细胞缺铁会损害线粒体功能，减少ATP合成，促进纤维化和炎症。mra可以通过恢复铁摄取和改善心肌能量来抵消这些影响。这一新兴的醛固酮-铁轴为MR激活对心脏的影响提供了新的见解，并将铁稳态确定为潜在的治疗靶点。mri介导的心肌铁代谢调节有待进一步研究。

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引用次数: 0

White kidney bean extract improves letrozole-induced polycystic ovary syndrome in rats by regulating the Wnt signaling pathway 白芸豆提取物通过调节Wnt信号通路改善来曲唑诱导的大鼠多囊卵巢综合征

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-01-01 Epub Date: 2025-09-07 DOI: 10.1016/j.jsbmb.2025.106858

Jiani Zhu , Ran Gu , Ya Zhu , Qun Zhou , Zijuan Zhang , Xinyue Qi , Xiaorong Wu , Bo Deng , Lanping Zhong

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder characterized by ovarian dysfunction, with limited effective treatments. This study investigates the therapeutic effects and mechanisms of white kidney bean extract (WKBE) in a PCOS rat model. A PCOS model was established using letrozole, followed by intervention with varying doses of WKBE. Serum sex hormone levels, insulin resistance, and metabolic markers were measured. Ovarian histopathology, fibrosis, and apoptosis were assessed. Transcriptomic sequencing was performed on ovarian tissues from control, PCOS, and high-dose WKBE groups. High-dose WKBE significantly ameliorated endocrine-metabolic disturbances in PCOS rats, including reduced testosterone, LH/FSH ratio, insulin resistance, and lipid abnormalities, outperforming low/medium doses. It decreased body weight, ovarian index, and organ fat deposition, repaired ovarian histopathological damage, and reduced fibrosis and apoptosis. Transcriptomic analysis revealed that high-dose WKBE altered the expression of Wnt signaling pathway-related genes, suggesting its therapeutic role may involve modulation of this pathway. High-dose WKBE alleviates endocrine-metabolic dysregulation and ovarian dysfunction in PCOS rats by regulating the Wnt signaling pathway, offering a potential novel therapeutic strategy.

多囊卵巢综合征（PCOS）是一种以卵巢功能障碍为特征的内分泌代谢疾病，有效治疗方法有限。本研究探讨白芸豆提取物（WKBE）对PCOS大鼠模型的治疗作用及其机制。用来曲唑建立多囊卵巢综合征模型，然后用不同剂量的WKBE进行干预。测定血清性激素水平、胰岛素抵抗和代谢指标。评估卵巢组织病理学、纤维化和细胞凋亡。对对照组、PCOS组和高剂量WKBE组的卵巢组织进行转录组测序。高剂量WKBE显著改善PCOS大鼠的内分泌代谢紊乱，包括降低睾酮，LH/FSH比率，胰岛素抵抗和脂质异常，优于低/中剂量。降低体重、卵巢指数和器官脂肪沉积，修复卵巢组织病理损伤，减少纤维化和细胞凋亡。转录组学分析显示，高剂量WKBE改变了Wnt信号通路相关基因的表达，提示其治疗作用可能与调节该通路有关。大剂量WKBE通过调节Wnt信号通路减轻PCOS大鼠内分泌代谢失调和卵巢功能障碍，为PCOS大鼠提供了一种潜在的新型治疗策略。

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引用次数: 0

POMC mediates orofacial hyperalgesia under hypoestrogenic conditions POMC介导低雌激素条件下的口面部痛觉过敏。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-01-01 Epub Date: 2025-09-12 DOI: 10.1016/j.jsbmb.2025.106861

Cong Chen , Linqian Zhang , Wenjuan Wang , Yanrong Sun , Yu Bai , Qinhan Yao , Shuo Qin , Lihua Qin , Jing Jia

Estrogen modulates sensory neuron excitability via metabolic pathways, regulating women's pain perception. pro-opiomelanocortin (POMC), an endogenous polypeptide precursor, regulates pain response and is highly expressed in the trigeminal ganglion (TG). In this study, we used ovariectomized female rats to study how trigeminal ganglion POMC links to orofacial allodynia in hypoestrogenic state, and verified at both the gene and protein levels that the expression of POMC in the trigeminal ganglion decreased under the hypoestrogenic state. Subsequently, overexpressing the POMC gene in the TG reversed the pain hyperalgesia in ovariectomized rats. To further explore the regulatory mechanism of estrogen on POMC, we injected a selective estrogen receptor agonist at the trigeminal ganglion. Estradiol (E2) in the TG regulates the expression of POMC through estrogen receptor α (ERα). Subsequently, the Chromatin Cleavage and Tagging technology (CUT&Tag) and the dual-luciferase assay revealed that estrogen receptor α in the trigeminal ganglion has a positive regulatory effect on the promoter of POMC. In conclusion, this study has found that in the trigeminal ganglion, estrogen receptor α may reduce the expression of the POMC gene by inhibiting the activity of the POMC promoter. Meanwhile, this study has also found that in the TG, ERα may further regulate the biological activity of the POMC protein by binding to it. This dual regulation at both the transcriptional level and the protein level collectively mediates a decrease in the orofacial mechanical pain threshold and triggers an orofacial allodynia response.

雌激素通过代谢途径调节感觉神经元的兴奋性，调节女性的疼痛感知。opiomelanocortin （POMC）是一种内源性多肽前体，调节疼痛反应，并在三叉神经节（TG）中高度表达。在本研究中，我们利用去卵巢的雌性大鼠研究了低雌激素状态下三叉神经节POMC与口面异痛症的联系，并在基因和蛋白水平上证实了低雌激素状态下三叉神经节POMC的表达减少。随后，在TG中过表达POMC基因逆转了去卵巢大鼠的痛觉过敏。为了进一步探讨雌激素对POMC的调控机制，我们在三叉神经节处注射选择性雌激素受体激动剂。甘油三酯中的雌二醇（E2）通过雌激素受体α (ERα)调节POMC的表达。随后，染色质切割和标记技术（CUT&Tag）和双荧光素酶实验发现三叉神经节雌激素受体α对POMC启动子具有正调控作用。综上所述，本研究发现，在三叉神经节中，雌激素受体α可能通过抑制POMC启动子的活性来降低POMC基因的表达。同时，本研究还发现，在TG中，ERα可能通过与POMC蛋白结合，进一步调节POMC蛋白的生物活性。这种转录水平和蛋白质水平的双重调控共同介导了口面机械痛阈的降低，并引发了口面异常性痛反应。

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引用次数: 0

Inhibition of 14–3-3 protein enhances steroid hormone production and oxidative stress in mouse ovary: Implications for apoptosis regulation 14-3-3蛋白抑制小鼠卵巢类固醇激素产生和氧化应激：凋亡调控的意义。

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology

Pub Date : 2026-01-01 Epub Date: 2025-09-28 DOI: 10.1016/j.jsbmb.2025.106869

Shatrudhan Upadhyay , Namrata Dubey , Aanya Singh

The ovary is a primary reproductive organ where the fine balance between steroidogenesis, oxidative stress, and apoptosis governs female reproductive health. A highly conserved protein, 14–3–3, is known to influence steroid biosynthesis, redox balance, and cell survival; however, its integrative role in ovarian physiology remains poorly defined. This study investigated the consequences of pharmacological inhibition of 14–3–3 protein using BV02 in in vitro cultured mouse ovaries. Immunohistochemical analysis revealed strong expression of 14–3–3 in granulosa cells, with moderate expression in oocytes and theca cells. In the BV02-treated ovary (100 μM), there was significant elevation in the levels of ovarian progesterone, testosterone, and estradiol, indicating enhanced steroidogenesis. However, the treated ovaries showed decreased activity of catalase and superoxide dismutase (SOD), along with increased lipid peroxidation (TBARS), indicating increased oxidative stress. Western blot analysis showed downregulation of the anti-apoptotic protein Bcl-2 together with elevated levels of the pro-apoptotic protein Caspase-3, signifying a molecular shift toward apoptosis. Correlation analysis further established strong associations (p < 0.05) between oxidative stress markers and apoptotic regulators, highlighting a mechanistic link between impaired antioxidant defenses and apoptosis. These findings reveal that 14–3–3 protein acts as a dual regulator of ovarian physiology by restraining steroid hormone production in addition to maintaining redox balance and cell survival. Disruption of this equilibrium may lead to pathological states such as polycystic ovary syndrome (PCOS) and ovarian cancer. Thus, this study provides novel mechanistic insights into the regulatory role of 14–3–3 protein in the ovary and underscores its potential as a therapeutic target in reproductive disorders.

卵巢是主要生殖器官，甾体生成、氧化应激和细胞凋亡之间的良好平衡支配着女性生殖健康。已知高度保守的14-3-3蛋白影响类固醇生物合成、氧化还原平衡和细胞存活；然而，其在卵巢生理中的综合作用仍不明确。本研究探讨了BV02对体外培养小鼠卵巢14-3-3蛋白的药理抑制作用。免疫组化分析显示14-3-3在颗粒细胞中强表达，在卵母细胞和卵泡细胞中有中等表达。在bv02处理的卵巢（100μM）中，卵巢黄体酮、睾酮和雌二醇水平显著升高，表明类固醇生成增强。然而，处理后的卵巢过氧化氢酶和超氧化物歧化酶（SOD）活性下降，脂质过氧化（TBARS）升高，表明氧化应激增加。Western blot分析显示，抗凋亡蛋白Bcl-2下调，促凋亡蛋白Caspase-3水平升高，表明细胞向凋亡的分子转移。相关分析进一步确立了强关联(p

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引用次数: 0