Journal of Steroid Biochemistry and Molecular Biology最新文献

{"title":"Causal influences of testosterone on brain structure change rate: A sex-stratified Mendelian randomization study","authors":"Xin Lian ,&nbsp;Yaqi Bai ,&nbsp;Pengyang Du ,&nbsp;Zhinan Jing ,&nbsp;Jimi Gao ,&nbsp;Fan Liu ,&nbsp;Jingjing Hu ,&nbsp;Yujia Xi","doi":"10.1016/j.jsbmb.2024.106629","DOIUrl":"10.1016/j.jsbmb.2024.106629","url":null,"abstract":"<div><div>The impact of testosterone levels on changes in brain structure has been reported. However, it is still unclear which specific brain region could be affected. This study approached Mendelian randomization method to reveal the causal relationship between testosterone levels and the rate of longitudinal structural changes in the brain. The testosterone-related GWAS data were determined from 425,097 European participants. The GWAS data on the rate of longitudinal structural changes in the brain came from the ENIGMA consortium, which included 15,640 all-age participants from 40 longitudinal cohorts. The inverse variance weighted was considered as the main estimate, MR Egger and weighted median methods were used to supplement IVW. A positive correlation was found between total testosterone levels and bioavailable testosterone levels in women and age-independent longitudinal changes in cerebral WM and surface area. The sex hormone-binding globulin levels were found a negative correlation with age-dependent longitudinal structural changes of cortical GM in men. Additionally, we also found that the bioavailable testosterone level in males was negatively associated with the quadratic age-dependent longitudinal change rate in the globus pallidum. We also found estradiol levels and sex hormone-binding globulin levels were negatively associated with the quadratic age-dependent longitudinal change rate of total brain in men. Moreover, we found a positive correlation between total testosterone levels and linear age-dependent longitudinal changes in the hippocampus in both males and females. The testosterone levels in different genders may have varying degrees of causal effects on the structural changes of brain regions. These findings provide evidence for the influence of the brain glandular axis on brain structure, particularly during female brain development.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic inhibitory effects of tetramethylpyrazine and evodiamine on endometriosis development","authors":"Xiaohan Liu ,&nbsp;Qingjun Shen ,&nbsp;Liqin Cheng,&nbsp;Kailing Dai,&nbsp;Qiaozhu Wu,&nbsp;Xiaole Liu,&nbsp;Paul Yao,&nbsp;Liqin Zeng","doi":"10.1016/j.jsbmb.2024.106630","DOIUrl":"10.1016/j.jsbmb.2024.106630","url":null,"abstract":"<div><div>Endometriosis (EMS) belongs to a gynecological disorder with inflammation and the existence of endometrial-like tissues beyond the uterus, often leading to infertility and pelvic pain. Estrogen receptor β (ERβ) is significantly expressed in endometriosis (EMS) and recognized as a promising therapeutic target for EMS treatment by inhibiting ERβ activity. In this study, we investigated the potential mechanisms for tetramethylpyrazine (TMP)-mediated ERβ suppression, and the synergistic inhibitory effect of TMP and evodiamine (EVO) on ERβ expression and EMS development. We found that TMP suppresses ERβ expression by reducing the association of Oct3/4 with the ERβ promoter and decreasing Oct3/4 protein levels without affecting Oct3/4 transcript levels. A minimum dosage of 10 µM TMP is required to inhibit ERβ expression. Neither TMP (5 µM) nor EVO (2 µM) alone had any effect, but their combination synergistically inhibited ERβ expression and modulated related cellular processes, including redox balance, mitochondrial function, inflammation, and proliferation. Additionally, the combination of TMP (10 mg/kg body weight) and EVO (5 mg/kg) synergistically inhibited ERβ expression and EMS development in the mouse model. In conclusion, TMP suppresses ERβ expression by reducing the association of Oct3/4 with the ERβ promoter. Neither TMP nor EVO alone effectively suppresses ERβ in both laboratory and live organism models. However, their combination synergistically inhibits ERβ expression and EMS development, suggesting a potential therapeutic strategy for EMS using TMP and EVO.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical classification diagnosis of polycystic ovary syndrome based on serum steroid hormones","authors":"Min Wang ,&nbsp;Shuhan Zhang ,&nbsp;Jun He ,&nbsp;Tianqi Zhang ,&nbsp;Huaijun Zhu ,&nbsp;Runbin Sun ,&nbsp;Na Yang","doi":"10.1016/j.jsbmb.2024.106626","DOIUrl":"10.1016/j.jsbmb.2024.106626","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is a metabolic disorder with clinical heterogeneity. PCOS women with non-hyperandrogenemia (NA) might be misdiagnosed due to a lack of diagnostic markers. This study aims to systematically analyze the differences in steroid hormones between PCOS women with hyperandrogenemia (HA) and NA, and to screen classification diagnosis models for PCOS. The serum samples from 54 HA-PCOS, 79 NA-PCOS and 60 control women (Non-PCOS) aged between 18 and 35 were measured by an integrated steroid hormone-targeted quantification assay using LC-MS/MS. The levels of serum androgens, corticosteroids, progestins and estrogens in the steroid hormone biosynthesis pathway were analyzed in PCOS and Non-PCOS women. Eight machine learning methods including Linear Discriminant Analysis (LDA), K-nearest Neighbors (KNN), Boosted Logistic Regression (LogitBoost), Naive Bayes (NB), C5.0 algorithm (C5), Random Forest (RF), Support Vector Machines (SVM), and Neural Network (NNET) were performed, evaluated and selected for classification diagnosis of PCOS. A 10-fold cross-validation on the training set was performed. The whole metabolic flux from cholesterol to downstream steroid hormones increased significantly in PCOS, especially in HA-POCS women. The RF model was chosen for the classification diagnosis of HA-PCOS, NA-PCOS, and Non-PCOS women due to the maximum average accuracy (0.938, <em>p</em>&lt;0.001), AUC (0.989, <em>p</em>&lt;0.001), and kappa (0.906, <em>p</em>&lt;0.001), and the minimum logLoss (0.200, <em>p</em>&lt;0.001). Five steroid hormones including testosterone, androstenedione, total 2-methoxyestradiol, total 4-methoxyestradiol, and free estrone were selected as the decision trees for the simplified RF model. A total of 37 women were included in the validation set. The diagnostic sensitivity for HA-PCOS, NA-PCOS, and Non-PCOS was 100 %, 93.3 % and 91.7 %, respectively. HA-PCOS, NA-PCOS, and Non-PCOS women showed obvious different steroid hormone profiles. The simplified RF model based on two androgens and three estrogens could be effectively applied to the classification diagnosis of PCOS, further reducing the missed diagnosis rate of NA-PCOS.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An optimized whole-body corticosteroid hormones quantification method by LC-MS/MS for assessing stress levels in European glass eels (Anguilla anguilla)","authors":"Stellia Sebihi ,&nbsp;Mathilde Monperrus ,&nbsp;Pascale Coste ,&nbsp;Emmanuel Huchet ,&nbsp;Matthieu Lingrand ,&nbsp;Stéphane Glise ,&nbsp;Colin Bouchard ,&nbsp;Maren Ortiz-Zarragoitia ,&nbsp;Valérie Bolliet","doi":"10.1016/j.jsbmb.2024.106627","DOIUrl":"10.1016/j.jsbmb.2024.106627","url":null,"abstract":"<div><div>The European eel (<em>Anguilla anguilla</em>) juvenile stage exhibits facultative estuarine migration. The causes of this behavior are yet unknown but it may have an impact on the population's fate by altering the sex ratio of the population. Recent studies have highlighted potential stress-related issues in glass eels settling in estuaries but studying stress response in small organisms requires sensitive, accurate and precise analytical methods. The aims of the present study are (i) to develop a whole-body Liquid Chromatography-Mass Spectrometry (LC-MS/MS) method for the simultaneous determination of several stress hormones in low-body mass fish; (ii) to apply this method to glass eels to study their responses to acute stress (iii) to test the effect of anxiolytics (diazepam) on these responses. Our results showed that enhanced LC-MS/MS analysis reduced detection limits and improved accuracy and precision for the quantification at the individual level. Following an acute stress, cortisol concentration significantly increased in glass eels and a 15 h diazepam exposure significantly reduced cortisol levels highlighting a marked anxiolytic effect on this species.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protopanaxadiol synergizes with glucocorticoids to enhance the therapeutic effect in adriamycin-induced nephrotic syndrome.","authors":"Ming-Yan Yang, Dong Qi, Meng-Ying Wang, Da-Lei Li, Zhen-Yuan Li, Ya-Ping He, Ke Liu, Hua-Ying Fan","doi":"10.1016/j.jsbmb.2024.106628","DOIUrl":"10.1016/j.jsbmb.2024.106628","url":null,"abstract":"<p><p>To date, glucocorticoids remain the mainstay of treatment of nephrotic syndrome (NS). However, serious side effects and development of drug-resistance following long-term use limit the application of glucocorticoids. Protopanaxadiol (PPD) possesses activity of dissociating transactivation from transrepression by glucocorticoid receptor (GR), which may serve as a potential selective GR modulator. However, steroid-like effects of PPD in vivo are unclear and not defined. How to translate PPD into clinical practice remains to be explored. The current study explored the renoprotection and potential mechanism of PPD and its combination with steroid hormones using adriamycin-induced NS rats. Adriamycin was given intravenously to rats to induce nephropathy. The determination of proteinuria, biochemical changes and inflammatory cytokines were performed, and pathological changes were examined by histopathological examination. Immunostaining and PCR were used to analyze the expression of interesting proteins and genes. The results showed that PPD, alone and in combination with prednisone, efficiently alleviate the symptoms of NS, attenuate nephropathy, improve adriamycin-induced podocyte injury by reducing desmin and increasing synaptopodin expression. In addition, the combined treatment reduced the expression of NF-κB protein and mRNA, as well as cytokine levels, and yet increased the expression of GR protein and mRNA. PPD modulated the transactivation of GR, manifested as repressing TAT, PEPCK and ANGPTL4 mRNA expressions mediated by GR. Meanwhile, PPD inhibited elevation of blood glucose and immune organ atrophy induced by prednisone. In summary, PPD increases the therapeutic effect of prednisone in NS while effectively prevents or decreases the appearance of side effects of glucocorticoids.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay of calcium, vitamin D, and parathormone in the milieu of infections and immunity: Reassessed in the context of COVID-19","authors":"Upasana Bandyopadhyay ,&nbsp;Debanjana Sen ,&nbsp;Deepika Ahuja ,&nbsp;Smit Pratik Mahapatra ,&nbsp;Debjit Biswas ,&nbsp;Rajkumar Maiti ,&nbsp;Sutanu Chakraborty ,&nbsp;Anukona Hazra ,&nbsp;Suparna Parua ,&nbsp;Asim Kumar Basak ,&nbsp;Arnab Das ,&nbsp;Nimisha Paul ,&nbsp;Mahuya Patra Purkait ,&nbsp;Alak Kumar Syamal ,&nbsp;Rajen Dey ,&nbsp;Koushik Bhattacharya ,&nbsp;Krishnendu Adhikary ,&nbsp;Aniruddha Bhattacharjee","doi":"10.1016/j.jsbmb.2024.106624","DOIUrl":"10.1016/j.jsbmb.2024.106624","url":null,"abstract":"<div><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recognized for inducing severe respiratory symptoms like cough, and shortness of breathing. Although symptom severity varies, some individuals remain asymptomatic. This virus has sparked a global pandemic, imposing a substantial rate of mortality or morbidity, with extended periods of illness reported. People with underlying medical issues and the elderly are more likely to experience adverse results. The virus's frequent mutations pose challenges for medical professionals, necessitating adaptable therapeutic and preventive strategies. Vitamin D, a versatile regulatory molecule, not only influences physiological processes such as serum calcium regulation but also exhibits immunomodulatory functions. Calcium ions play a crucial role as secondary signal transduction molecules, impacting diverse cellular functions and maintaining homeostasis through ion channel regulation. Parathormone, another key regulator of serum calcium, often acts antagonistically to vitamin D. This review delves into the interplay of vitamin D, calcium, and parathormone, exploring their possible influence on the progression of COVID-19. The intricate signaling involving these elements contributes to adverse prognosis, emphasizing the need for comprehensive understanding. Monitoring and controlling these physiological factors and associated pathways have shown the potential to alter disease outcomes, underscoring the importance of a holistic approach.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KaiXinSan improves learning and memory impairment by regulating cholesterol homeostasis in mice overloaded with 27-OHC","authors":"Rui Jing ,&nbsp;Lihua Mu ,&nbsp;Chaochen Wang ,&nbsp;Lijun Liu ,&nbsp;Yanbo Wang ,&nbsp;Yuanbo Wang ,&nbsp;Xia Li ,&nbsp;Hong Yin ,&nbsp;Yuan Hu","doi":"10.1016/j.jsbmb.2024.106622","DOIUrl":"10.1016/j.jsbmb.2024.106622","url":null,"abstract":"<div><div>Cholesterol and its oxidative products—oxysterols homeostasis— play a crucial role in maintaining cognitive function. Chinese medicine KaiXinSan (KXS) has demonstrated effectiveness in treating mental illness and regulating cognitive dysfunction of Alzheimer's disease (AD). The purpose of this article is to explore whether the KXS can enhance cognitive function by regulating cholesterol homeostasis. Employing the 27-hydroxy cholesterol (27-OHC) induced mice model of cognitive dysfunction and coculture model of assessment neurocyte damage, we investigated learning and memory abilities while concurrently addressing the reduction of neuronal cell damage through the regulation of cholesterol metabolism. 21 days of KXS treatment improved the learning and memory ability in mice 27-OHC-overloading by alleviating the exacerbated deposition of amyloid-β (Aβ), reducing inflammatory reactions, and mitigating synaptic plasticity damage. Additionally, it repaired myelin sheath function. More importantly, KXS significantly affects the metabolism of central cholesterol by substantially inhibiting the expression of liver X receptor (LXR), ATP-binding cassette transporter (ABCA1, ABCG1), apolipoprotein E (ApoE) and upregulated cytochrome P450 46A1(CYP46A1). Furthermore, KXS may alleviate 27-OHC-induced neuronal inflammation and apoptosis by promoting the conversion of cholesterol to 24-hydroxycholesterol (24-OHC) via CYP46A1 and suppressing cholesterol release from astrocyte cells. Altogether, our results demonstrate that KXS can prevent learning and memory impairments induced by 27-OHC loading. This effect may be related to its multitarget capability in promoting the conversion of excessive cholesterol to 24-OHC and maintaining a balance in cholesterol homeostasis and metabolism between neurons and astrocyte cells.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances and challenges in liquid chromatography-spectrometry (LC-MS) methodology for quantifying androgens and estrogens in human serum and plasma","authors":"Qingqing Wang,&nbsp;Clementina Mesaros","doi":"10.1016/j.jsbmb.2024.106618","DOIUrl":"10.1016/j.jsbmb.2024.106618","url":null,"abstract":"<div><div>Accurate quantification of androgens and estrogens is critical for elucidating their roles in endocrine disorders and advancing research on their functions in human biology and pathophysiology. This review highlights recent advances and ongoing challenges in liquid chromatography- mass spectrometry (LC- MS) methodology for quantifying androgens and estrogens in human serum and plasma. We summarized current approaches for analyzing the different forms of androgens and estrogens, along with their reported levels in publications from 2010 to the present. These published levels pointed out the inconsistencies in reference intervals across studies. To address these issues, advances in derivatization methods and chromatographic separation techniques are reviewed. Future perspectives for improving the accuracy and consistency of hormone quantification in clinical and research settings were also proposed.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are androgen receptor agonists a treatment option in bladder cancer?","authors":"Michael L. De Ieso ,&nbsp;Ahmed Faris Aldoghachi ,&nbsp;Wayne D. Tilley,&nbsp;Amy R. Dwyer","doi":"10.1016/j.jsbmb.2024.106623","DOIUrl":"10.1016/j.jsbmb.2024.106623","url":null,"abstract":"<div><div>Sex-related differences in bladder cancer incidence and progression infer a role for sex hormones and their cognate receptors in this disease. In part due to the oncogenic role of androgen receptor signaling in prostate cancer, the focus of most preclinical and clinical research to-date has been on the potential pro-tumorigenic action of androgens in urothelial cancers. However, clinical studies of androgen receptor antagonism have yielded minimal success. In this review, we explore the tumor suppressor role of androgen receptor in bladder cancer and discuss how it might be harnessed therapeutically.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unique sterol metabolite shifts in inflammatory bowel disease and primary sclerosing cholangitis","authors":"Silke Matysik ,&nbsp;Tanja Elger ,&nbsp;Muriel Huss ,&nbsp;Gerhard Liebisch ,&nbsp;Marcus Höring ,&nbsp;Johanna Loibl ,&nbsp;Arne Kandulski ,&nbsp;Martina Müller ,&nbsp;Hauke Christian Tews ,&nbsp;Christa Buechler","doi":"10.1016/j.jsbmb.2024.106621","DOIUrl":"10.1016/j.jsbmb.2024.106621","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) triggers chronic intestinal inflammation and is linked to primary sclerosing cholangitis (PSC). Cholesterol homeostasis, tightly regulated under normal conditions, becomes disrupted in both inflammation and chronic liver disease. We analyzed fecal and serum levels of cholesterol synthesis precursors, oxysterols, and phytosterols in 87 patients with IBD (81 for serum analysis) including patients with Crohn's disease (CD) and ulcerative colitis (UC), 11 patients with PSC, 21 patients with PSC-IBD (18 for serum analysis), and 16 healthy controls (17 for serum analysis). Cholesterol was analysed by flow injection analysis on a high-resolution hybrid quadrupole-Orbitrap mass spectrometer and further serum sterols and all fecal sterols were analysed by a gas chromatograph mass spectrometer. Serum levels of lanosterol, 7-dehydrocholesterol, 7-beta-hydroxycholesterol, 27-hydroxycholesterol, and the plant sterols campesterol, stigmasterol, and sitosterol were similar across control and patient groups. Notably, serum lathosterol was elevated in CD patients compared to those with UC, PSC, PSC-IBD, and healthy controls. All other serum and fecal sterols showed no differences between CD and UC. Cholesterol synthesis precursors in serum, serum cholesterol levels, and both serum and fecal plant sterol levels decreased with increasing IBD severity. Consequently, serum cholesterol, campesterol, sitosterol, and fecal 5-beta sitostanol and 5-alpha sitostanol were negatively correlated with C-reactive protein and fecal calprotectin. The conversion of cholesterol to coprostanol in feces was impaired in IBD, PSC, and PSC-IBD, independent of bowel inflammation severity or liver disease extent. Patients with PSC, and to a lesser extent PSC-IBD, had elevated serum plant sterol levels, positively correlating with liver disease markers. In conclusion, in patients with IBD, cholesterol biosynthetic precursors, serum cholesterol levels, and fecal plant sterols decrease with intestinal inflammation. An inverse association of serum plant sterols with intestinal inflammation was observed in patients with IBD and a direct association of serum phytosterols with liver injury in patients with PSC. The conversion of fecal cholesterol to coprostanol was impaired in all patient cohorts. IBD and PSC alter serum sterol levels differently, whereas changes in fecal sterols are not disease specific and are moderate.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0960076024001699/pdfft?md5=408dbeec60ad16970264b5efd01f971b&pid=1-s2.0-S0960076024001699-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}