Journal of Steroid Biochemistry and Molecular Biology最新文献

{"title":"Continuous flow-through steady state system for in vitro characterization of CYP11B2 inhibitors–Impact on enzyme kinetics of steroidogenesis","authors":"Dennis Fröbel ,&nbsp;Stefanie Hahner ,&nbsp;Britta Heinze ,&nbsp;Peter Dieterich ,&nbsp;Georgiana Constantinescu ,&nbsp;Sanas Mir-Bashiri ,&nbsp;Tracy Ann Williams ,&nbsp;Mirko Peitzsch ,&nbsp;Graeme Eisenhofer ,&nbsp;Andreas Schirbel ,&nbsp;Nicole Bechmann","doi":"10.1016/j.jsbmb.2025.106736","DOIUrl":"10.1016/j.jsbmb.2025.106736","url":null,"abstract":"<div><h3>Background</h3><div>The homology of aldosterone- and cortisol-producing enzymes, aldosterone synthase (CYP11B2) and 11β-hydroxylase, complicates identification of selective CYP11B2 inhibitors required for antihypertensive treatment or for imaging approaches in patients with primary aldosteronism. To improve preclinical evaluation of novel CYP11B2-targeting compounds, we developed a flow-through cell culture system that provides insights into kinetics of steroidogenesis and inhibitory responses at CYP11B2 active sites.</div></div><div><h3>Methods</h3><div>NCI-H295RA and HAC-15 cells were cultured in ibidi flow chambers under constant culture medium flow. Supernatants were collected hourly before and after treatment with (<em>R</em>)-1-[1-(4-iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinylamide (IMAZA), a non-selective CYP11B1/B2 inhibitor, or the potential CYP11B2 inhibitors ID-69 and ID-191. Steroid profiles were analyzed by liquid chromatography-tandem mass spectrometry. Steady state approximation in steroidogenesis allowed mathematical modeling-based calculation of metabolic fluxes and relative rate constants of biocatalytic steps.</div></div><div><h3>Results</h3><div>An optimized flow-through system is now available to characterize inhibitory responses at the three catalytic sites of CYP11B2 in two steroid-producing cell lines. IMAZA non-selectively inhibited CYP11B 11β-hydroxylase function, while ID-69 and ID-191 affected the CYP11B2-specific 18-hydroxylase active site with minor effects on catalytic activity of 11β-hydroxylase. ID-191 simultaneously impaired catalytic activity of cortisol production, whereas ID-69 was highly selective for CYP11B2 inhibition.</div></div><div><h3>Conclusion</h3><div>Our flow-through system provides insights into inhibitor-induced alterations of metabolic fluxes and enzymatic rate constants, and thus represents an improved preclinical model sytem for complex characterization of CYP11B2 inhibitors.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106736"},"PeriodicalIF":2.7,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659132","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":"Clinical trials of vitamin D supplementation and cardiovascular disease: A synthesis of the evidence","authors":"Robert Scragg","doi":"10.1016/j.jsbmb.2025.106733","DOIUrl":"10.1016/j.jsbmb.2025.106733","url":null,"abstract":"<div><div>The evidence linking vitamin D deficiency with increased risk of cardiovascular disease (CVD) extends back to 1970s when case control studies showed lower circulating concentrations of 25-hydroxyvitamin D [25(OH)D] in myocardial infarction cases compared with controls, which was strengthened by the identification of a vitamin D receptor in cardiac muscle in 1980s. Cohort studies published in the 2000s provided stronger evidence (by measuring 25(OH)D concentrations before the onset of CVD) and confirmed the inverse association between circulating 25(OH)D concentrations and CVD risk. However, concerns remained about possible residual confounding as the reason for the inverse association. This stimulated the initiation of several large scale randomized controlled trials (RCTs) of vitamin D supplementation with CVD as a pre-specified outcome. Results from these studies have been combined with findings from earlier RCTs in a recent meta-analysis undertaken on behalf of the US Endocrine Society. In 14 RCTs with 80,547 participants aged 50–74 years, vitamin D supplementation did not protect against CVD when compared to placebo: risk ratio 1.00 (95 % confidence interval 0.93–1.08). This result did not vary by study quality (risk of bias), gender, calcium co-administration, vitamin D dose or trial setting (community or residential care). This finding is consistent with recent mendelian randomization studies which have not detected a beneficial effect associated with genetically predicted 25(OH)D in people with vitamin D deficiency. Overall, the current evidence indicates that vitamin D does not prevent CVD.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106733"},"PeriodicalIF":2.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651987","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":"Chronic intake of Dioscorea esculenta suppresses testicular atrophy, enhances the ability of protection from inflammation in type 2 diabetes rats","authors":"Koki Tatara ,&nbsp;Koji Sato","doi":"10.1016/j.jsbmb.2025.106730","DOIUrl":"10.1016/j.jsbmb.2025.106730","url":null,"abstract":"<div><div><em>Dioscorea esculenta</em> increases sex steroid hormones in obesity and type 2 diabetes that impairs steroidogenesis. However, the effects of chronic <em>D. esculenta</em> intake on testicular sex steroid hormone concentrations and testicular function especially protection from oxidative stress and inflammation is still unclear. The study assessed the effects of chronic <em>D. esculenta</em> intake and exercise training on testicular function in rats with type 2 diabetes. Twenty-week-old Otsuka Long-Evans Tokushima Fatty rats were randomly assigned to the control, exercise training (running at 25 m/min for 1 h, 5 days/week), and <em>D. esculenta</em> intake (0.3 % with normal feed) groups (n = 8 per group). Long-Evans Tokushima Otsuka rats served as the healthy controls (n = 7). Eight weeks of <em>D. esculenta</em> intake or exercise training significantly increased plasma concentrations of dehydroepiandrosterone (DHEA), free testosterone and 5α-dihydrotestosterone (DHT). No significant increases were observed in DHEA, testosterone, and DHT concentrations in the testis. Androgen receptor (AR) expression was significantly increased by <em>D. esculenta</em> intake and exercise training. The expression of cathepsin L, which is involved in sperm modification, did not significantly change, whereas the expression of glutathione peroxidase 4 (GPx4), which protects sperms from oxidative stress, significantly increased in the <em>D. esculenta</em> group. Additionally, metabolic clearance rate (MCR), an index of insulin resistance, significantly correlated with testicular weight and GPx4 expression. These results suggest that improvement in MCR through <em>D. esculenta</em> intake suppresses testicular atrophy and enhances the ability of protection from oxidative stress and inflammation in rats with type 2 diabetes.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106730"},"PeriodicalIF":2.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642700","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":"Kidney deletions of Cyp27b1 fail to reduce serum 1,25(OH)2D3","authors":"Seong Min Lee ,&nbsp;Shannon R. Cichanski ,&nbsp;Nicolas G. Pintozzi ,&nbsp;Martin Kaufmann ,&nbsp;Glenville Jones ,&nbsp;Mark B. Meyer","doi":"10.1016/j.jsbmb.2025.106734","DOIUrl":"10.1016/j.jsbmb.2025.106734","url":null,"abstract":"<div><div>Vitamin D metabolism is controlled through the kidney mitochondrial P450 enzymes 1α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24A1) that activate and degrade the endocrine vitamin D hormone (1,25(OH)₂D₃), respectively. We recently demonstrated that extrarenal cells can make 1,25(OH)₂D₃ with adequate vitamin D supplementation by targeted mass spectrometry imaging in our <em>Cyp27b1</em> kidney enhancer deletion mouse model that lacks circulating 1,25(OH)₂D₃ (M1/M21-DIKO mouse). Based on these observations, we selectively deleted <em>Cyp27b1</em> (<em>Cyp27b1</em>^fl/fl) from the mouse kidney using the <em>Six2-</em> and <em>Pax8-</em>cre drivers that target tubule and nephron development to see if we could recapitulate the remarkable phenotype of the M1/M21-DIKO mice. While <em>Six2</em>-cre/<em>Cyp27b1</em>^fl/fl mice had a mild phenotype, <em>Pax8</em>-cre/<em>Cyp27b1</em>^fl/fl mice had a marked elevation of parathyroid hormone and a reduction in bone mineral density. The vitamin D metabolic profile in the <em>Pax8</em>-cre/<em>Cyp27b1</em>^fl/fl clearly indicated a dysfunction in the CYP24A1 enzyme with reductions in 24,25(OH)₂D₃ and 25(OH)D₃-26,23-lactone with an accompanying elevation of 25(OH)D₃. However, despite these compensatory reductions in CYP24A1 derived metabolites and apparent deletion of <em>Cyp27b1</em> in the kidney, the 1,25(OH)₂D₃ levels were not changed from wildtype in either mouse. Like 24,25(OH)₂D₃, the 1,24,25(OH)₃D₃ levels were also reduced. These data highlight the robust homeostatic mechanisms to salvage 1,25(OH)₂D₃, point towards potential compensatory mechanisms of 1,25(OH)₂D₃ production from non-kidney tissues, and reinforce the utility of the M1/M21-DIKO model as a non-global deletion of <em>Cyp27b1</em> with reductions in serum 1,25(OH)₂D₃ to be used to understand the complexity of vitamin D metabolism in health and inflammatory disease.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106734"},"PeriodicalIF":2.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651990","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":"The impact of inducible-whole body or intestine-specific Cyp24a1 gene knockout on vitamin D metabolism in mice","authors":"James C. Fleet ,&nbsp;Natalie M. Watkins ,&nbsp;Paul H. Anderson ,&nbsp;Glenville Jones ,&nbsp;Martin Kaufmann","doi":"10.1016/j.jsbmb.2025.106735","DOIUrl":"10.1016/j.jsbmb.2025.106735","url":null,"abstract":"<div><div>Expression of 25 hydroxyvitamin D 24 hydroxylase from the <em>Cyp24a1</em> gene mediates 1,25 dihydroxyvitamin D (1,25(OH)₂D) catabolism but gaps exist in our understanding of this enzyme’s physiologic importance. Here, we used tamoxifen to induce <em>Cyp24a1</em> gene knockout (KO) in adult mice (50 mg Tamoxifen /g BW, ip, 5 d, at 11 wks of age) or intestinal-epithelial-cell-specific knock-out mice (IEC KO) to evaluate the role of CYP24A1 in adult mice and the contribution of the intestine to vitamin D (Vit D) metabolism. At 12-wks mice were euthanized and serum was analyzed for Vit D metabolites by LC MS/MS while duodenal (Dd) and kidney (Kd) mRNA levels were quantified using qPCR. Adult <em>Cyp24a1</em> KO mice had higher 25 hydroxyvitamin D (25(OH)D, + 185 %) and 1,25(OH)₂D (+41.4 %) levels and reduced levels of 1,24,25(OH)₃D (-53.7 %). No changes in serum Vit D metabolites were seen in adult mice lacking one <em>Cyp24a1</em> allele (HT). In kidney, compensatory changes in <em>Cyp27b1</em> mRNA (-85.3 % in KO, −36.5 % in HT) and <em>Cyp24a1</em> mRNA (+147 % in KO, +43 % in HT) were observed. No changes in Dd <em>Trpv6</em> or <em>S100g</em> mRNA were observed and Dd <em>Cyp3a13</em> mRNA did not compensate for <em>Cyp24a1</em> gene loss. Neither serum Vit D metabolites nor Dd <em>Trpv6</em> and <em>S100g</em> mRNA were changed in IEC KO mice but there was a trend towards elevated renal <em>Cyp24a1</em> mRNA (+61 %, p = 0.06). Our data in adult KO mice indicate that CYP24A1 has an important physiologic impact on Vit D metabolism while IEC KO data suggests that local degradation of the hormone by CYP24A1 is not a strong regulator of intestinal Vit D action or systemic vitamin D metabolism.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106735"},"PeriodicalIF":2.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651996","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":"The effect of vitamin D supplementation on cancer incidence in the randomised controlled D-Health Trial: Implications for policy and practice","authors":"Rachel E. Neale ,&nbsp;Dallas R. English ,&nbsp;Donald SA McLeod ,&nbsp;Bruce K. Armstrong ,&nbsp;Catherine Baxter ,&nbsp;Briony Duarte Romero ,&nbsp;Peter R. Ebeling ,&nbsp;Gunter Hartel ,&nbsp;Jolieke C. van der Pols ,&nbsp;Alison J. Venn ,&nbsp;Penelope M. Webb ,&nbsp;David C. Whiteman ,&nbsp;Mary Waterhouse","doi":"10.1016/j.jsbmb.2025.106738","DOIUrl":"10.1016/j.jsbmb.2025.106738","url":null,"abstract":"<div><div>Meta-analyses suggest that vitamin D supplementation reduces cancer mortality. As mortality is a function of incidence and survival, if use of vitamin D supplements does reduce cancer mortality, it must affect one or both of these parameters. Trials have found little evidence that vitamin D supplementation affects cancer incidence, but results were generally imprecise. We analysed data from the D-Health Trial, a randomised controlled trial of 60,000 IU of vitamin D₃ per month or matching placebo. 21,315 adults aged 60–85 years were recruited and supplemented for up to 5 years. We captured cancer diagnoses through linkage to state cancer registries. This analysis included 21,308 participants (vitamin D, n = 10,660; placebo, n = 10,648). The number of participants diagnosed with at least one cancer (excluding keratinocyte cancers) in the vitamin D and placebo groups was 1336 and 1304, respectively. We found no difference in cancer incidence between the two groups (HR 1.02; 95 % CI 0.95–1.10). Similarly, there was minimal difference when cutaneous melanomas were excluded (HR 1.04; 95 % CI 0.95–1.14). Analyses of individual cancers (prostate, breast, colorectal, lung, melanoma) did not demonstrate any effect of vitamin D, although the confidence intervals were relatively wide. These results provide convincing evidence to confirm the lack of effect of vitamin D on cancer incidence overall. The disconnect between effects on incidence and mortality would imply an effect on cancer survival. Determining whether any survival benefit is driven by vitamin D status prior to or after cancer diagnosis will be extremely challenging – indeed it may not be possible. Thus, it would be reasonable to consider whether population-wide supplementation or supplementation of cancer patients should be recommended now.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106738"},"PeriodicalIF":2.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651993","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":"Combined inhibition of importin-β and PBR enhances osteogenic differentiation of BMSCs by reducing nuclear accumulation of glucocorticoid receptor and promoting its mitochondrial translocation","authors":"Ying Deng ,&nbsp;Anhua Lin ,&nbsp;Chunhong Lai ,&nbsp;Wenjing He ,&nbsp;Jinfeng Li ,&nbsp;Na Zhang ,&nbsp;Shuijin Huang ,&nbsp;Lulu Tong ,&nbsp;Yufeng Lai ,&nbsp;Yanan Huo ,&nbsp;Jixiong Xu","doi":"10.1016/j.jsbmb.2025.106731","DOIUrl":"10.1016/j.jsbmb.2025.106731","url":null,"abstract":"<div><div>Excessive buildup of endogenous glucocorticoids has been closely linked to postmenopausal osteoporosis (PMOP), though the underlying mechanisms remain unclear. This study examines the role of glucocorticoid receptor (GR) signaling in PMOP, particularly its translocation to mitochondria, interaction with the peripheral benzodiazepine receptor (PBR), and impact on bone formation. <em>In vitro</em>, primary bone marrow mesenchymal stem cells (BMSCs) from mice were cultured to induce osteogenesis under varying concentrations of dexamethasone. Nuclear GR, mitochondrial GR, and PBR levels were measured, along with the effects of Importazole, an importin-β inhibitor, and Emapunil, a PBR inhibitor, on osteogenic differentiation. <em>In vivo</em>, ovariectomized mice were treated with Importazole and Emapunil to assess their anti-osteoporotic potential. Our results indicate that ovariectomized mice displayed increased nuclear GR, decreased mitochondrial GR, and elevated PBR expression in BMSCs. High dexamethasone impaired osteogenic differentiation, characterized by nuclear GR accumulation, reduced mitochondrial translocation, and increased PBR expression. Co-immunoprecipitation confirmed a direct interaction between mitochondrial GR and PBR. Importazole reduced nuclear GR levels, promoting bone formation and alleviating osteoporosis, while Emapunil enhanced GR mitochondrial translocation, improved mitochondrial function, and strengthened bone health. Combined, Importazole and Emapunil showed superior anti-osteoporotic effects compared to either treatment alone. These findings suggest that estrogen deficiency promotes nuclear GR accumulation and PBR expression in BMSCs, limiting GR mitochondrial translocation and reducing osteogenic differentiation. Combining Importazole and Emapunil could mitigate these effects, offering a promising therapeutic strategy for PMOP.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106731"},"PeriodicalIF":2.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626831","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":"Treatment response variations to a single large bolus of enteral cholecalciferol in vitamin D deficient critically Ill children: Metabolomic insights for precision nutrition","authors":"Erick Helmeczi ,&nbsp;Haley Pandya ,&nbsp;Katie O’Hearn ,&nbsp;Dayre McNally ,&nbsp;Philip Britz-McKibbin","doi":"10.1016/j.jsbmb.2025.106720","DOIUrl":"10.1016/j.jsbmb.2025.106720","url":null,"abstract":"<div><div>Vitamin D deficiency (VDD) is prevalent globally and in pediatric intensive care units, where it represents a modifiable risk factor that may impact patient recovery during hospitalization. Herein, we performed a retrospective analysis of serum samples from a phase-II randomized placebo-controlled trial involving a single large bolus of 10,000 IU/kg vitamin D3 ingested by critically ill children with VDD (25-OH-D &lt; 50 nmol/L). Targeted and untargeted methods were used to comprehensively measure 6 vitamin D metabolites, 239 lipids, 68 polar metabolites, and 4 electrolytes using a multi-step data workflow for compound authentication. Complementary statistical methods classified circulating metabolites/lipids associated with vitamin D repletion following high-dose vitamin D3 intake (n = 20) versus placebo (n = 11) comprising an optional standard of care maintenance dose (&lt; 1000 IU/day). There was a striking increase in median serum concentrations of 25-OH-D3 (4.7-fold), 3-<em>epi</em>-25-OH-D3 (24-fold) and their C3-epimer ratio (6.7-fold) in treated patients on day 3, whereas serum vitamin D3 peaked on day 1 (128-fold) unlike placebo. Treatment response differences were attributed to D3 bioavailability and C3-epimerase activity without evidence of hypercalcemia. For the first time, we report the detection of circulating 3-<em>epi</em>-D3 that was strongly correlated with vitamin D3 uptake (<em>r</em> = 0.898). Metabolomic studies revealed that vitamin D sufficiency (serum 25-OH-D &gt;75 nmol/L) coincided with lower circulating levels of 3-methylhistidine, cystine, <em>S</em>-methylcysteine, uric acid, and two lysophosphatidylcholines 7 days after treatment. Rapid correction of VDD was associated with indicators of lower oxidative stress, inflammation, and muscle protein turn-over that may contribute clinical benefits in high-risk critically ill children.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106720"},"PeriodicalIF":2.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598338","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":"Allopregnanolone in the pathogenesis of the psychiatric comorbidities of polycystic ovarian syndrome","authors":"Karis I. Sarkisian ,&nbsp;Jane L. Yang ,&nbsp;Christine Marshall ,&nbsp;Frank Z. Stanczyk","doi":"10.1016/j.jsbmb.2025.106719","DOIUrl":"10.1016/j.jsbmb.2025.106719","url":null,"abstract":"<div><div>Polycystic ovarian syndrome (PCOS) is an endocrine disorder affecting 10–15 % of women of reproductive age, with significant implications for both physical and mental health. Several recent research studies have examined the connection between PCOS and psychiatric disorders; however, the mechanism linking the two is not fully understood. Allopregnanolone is a neurosteroid that modulates GABA_A receptors and is naturally affected by the pathophysiology of PCOS. It is thought to play a role in mood disorders, including premenstrual dysphoric disorder and postpartum depression. Recent research has begun to focus on the relationship between PCOS and allopregnanolone. A literature review was conducted using databases, including PubMed, MEDLINE, and Cochrane Library. Keywords included “PCOS,” “psychiatric disorders,” “allopregnanolone,” and “neurosteroids.” Articles were selected based on relevance to psychiatric implications of PCOS, with a focus on high-quality, original research studies. Quality assessment of the sources was informed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) Handbook criteria. The literature review revealed a growing body of evidence suggesting a strong association between PCOS and an increased risk of psychiatric disorders, particularly depression, anxiety, and mood disorders. The role of allopregnanolone, a neurosteroid, was identified as an important factor in this relationship, with some studies indicating its potential impact on mood regulation in PCOS patients. There is a dire need for clinicians to consider the mental health implications of PCOS during diagnosis and management. The integration of psychiatric screening in PCOS management could lead to earlier detection and improved outcomes. Future research should focus on the therapeutic potential of allopregnanolone and other neurosteroids in treating psychiatric disorders associated with PCOS.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106719"},"PeriodicalIF":2.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598337","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":"Artifactual elevations of 11β-hydroxyandrostenedione and 11-ketoandrostenedione in mass spectrometry assays","authors":"Chaelin Lee ,&nbsp;Patrick O’Day ,&nbsp;David G. Stouffer ,&nbsp;Richard J. Auchus ,&nbsp;Adina F. Turcu","doi":"10.1016/j.jsbmb.2025.106717","DOIUrl":"10.1016/j.jsbmb.2025.106717","url":null,"abstract":"<div><div>Comprehensive steroid profiling by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) can be achieved using small biospecimen samples. LC-MS/MS assays offer superior accuracy to immunoassays, but they also introduce layers of complexity and opportunities for errors. Validation and harmonization studies are essential to ensure reliable results, as these assays are being increasingly incorporated in clinical laboratories. We developed an LC-MS/MS assay that simultaneously quantifies 18 Δ⁴ steroids, including mineralocorticoids, glucocorticoids, and androgens (both classic and 11-oxygenated androgens). Non-enzymatic conversion of cortisol and cortisone to 11β-hydroxyandrostenedione (11OHA4), and 11-ketoandrostenedione (11KA4), respectively, was assessed in dry and extracted human serum, and pure cortisol and cortisone solutions, at various temperatures and timepoints. We observed non-enzymatic conversion of cortisol and cortisone to 11OHA4 and 11KA4, respectively, in both human serum samples and pure cortisol and cortisone solutions at ambient temperature, and when incubated at 37 °C, but not at −20 °C. This phenomenon was amplified in dried steroids extracts, reaching 50-fold and 34-fold increase in 11OHA4 and 11KA4 peak areas, respectively. Non-enzymatic conversion of cortisol and cortisone to 11OHA4 and 11KA4 is a source of spurious LC-MS/MS results. Prompt steroid reconstitution on ice following solvent evaporation is required for accurate measurements of 11-oxyandrogens. Inter-laboratory harmonization of LC-MS/MS assays is needed to generate reliable results prior to clinical implementation.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106717"},"PeriodicalIF":2.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592015","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}