Alcohol (Hanover, York County, Pa.)最新文献

{"title":"Intimacy-driven conformity: A between- and within-person perspective on friendship quality and adolescent susceptibility to peer norms about alcohol.","authors":"Nathaniel J Caluda-Perdue, Rebecca A Schwartz-Mette, Craig R Colder","doi":"10.1111/acer.70179","DOIUrl":"https://doi.org/10.1111/acer.70179","url":null,"abstract":"<p><strong>Background: </strong>Friendships become increasingly influential in early adolescence, leading to a greater impact of friends' norms on behavior. However, not all youth conform to norms, suggesting other factors may shape this influence. One such factor is friendship quality, which may shape adolescents' motivation to adopt peer norms, especially when those norms come from close, supportive friendships. This study examined how perceptions of friends' alcohol use and approval predict adolescents' intentions to drink, and whether friendship quality moderates these effects while disaggregating between- and within-person effects using a multilevel, longitudinal design.</p><p><strong>Methods: </strong>Hierarchical linear modeling with a community sample of adolescents (n = 387) across 3 years tested hypotheses by distinguishing within- and between-person associations, capturing both the dynamic nature of friendships and how shifts in perceived norms influence alcohol intentions over time, as well as adolescents' broader tendency to affiliate with peers who approve of or engage in alcohol use. Interactions were tested using cross-product terms.</p><p><strong>Results: </strong>Results partially supported hypotheses suggesting that friendship quality impacted susceptibility to peer norms regarding perceptions of friends' approval (β = 0.28, p = 0.026) but not use (β = 0.22, p = 0.214). The models supported the decomposition of between- and within-person effects, as both friends' approval (between-person: β = 0.58, p < 0.001; within-person: β = 0.37, p < 0.001) and use (between-person: β = 0.61, p < 0.001; within-person: β = 0.29, p < 0.001) were positively associated with future intentions to drink.</p><p><strong>Conclusions: </strong>Taken together, results suggest that high-quality friendships amplified the influence of perceived friends' approval on alcohol intentions at the between-person level, but not for perceptions of use. Adolescents may prioritize maintaining their friendships; in turn, they adjust their beliefs and perceptions to preserve these relationships. Furthermore, perceptions of friends' alcohol norms operated similarly at the between- and within-level.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interactions between the bone morphogenetic protein and the planar cell polarity pathways lead to distinctive ethanol-induced facial defects.","authors":"Raèden Gray, Anna Lloyd, C Ben Lovely","doi":"10.1111/acer.70175","DOIUrl":"https://doi.org/10.1111/acer.70175","url":null,"abstract":"<p><strong>Background: </strong>Fetal alcohol spectrum disorders (FASD) describe a spectrum of ethanol-induced developmental defects. Ethanol susceptibility is modulated by genetics, but the underlying mechanisms remain poorly understood. In all vertebrates, complex cellular events give rise to the body plan, including gastrulation and morphogenesis of the endoderm and cranial neural crest (CNC-gives rise to the facial skeleton). These events are crucial for establishing complex signaling interactions that drive embryo development, including the formation of the facial skeleton. In zebrafish, gastrulation occurs between 6 and 10 h postfertilization (hpf), while endoderm/CNC morphogenesis occurs between 10 and 24 hpf. In previous work, planar cell polarity (PCP) mutants are ethanol-sensitive from 6 to 24 hpf (covering both gastrulation and endoderm/CNC morphogenesis), exhibiting multiple defects in the forming head. This raises the question of whether ethanol during both these time windows drives PCP-ethanol defects. We hypothesize that PCP mutants are ethanol-sensitive from 10 to 24 hpf, after gastrulation. We also hypothesize that bone morphogenetic protein (BMP) signaling (ethanol-sensitive 10-18 hpf) interacts with and sensitizes the PCP pathway to ethanol.</p><p><strong>Methods: </strong>We treated PCP/BMP mutants with ethanol over various time windows between 6 and 30 hpf and combined morphometric and linear measurements to examine facial development.</p><p><strong>Results: </strong>We show that PCP mutants are largely ethanol-sensitive from 10 to 24 hpf. We also show that BMP mutants sensitize PCP mutants to ethanol and lead to novel ethanol-independent midline craniofacial defects. Our results suggest that the ethanol-sensitive role of the PCP pathway occurs after gastrulation, during endoderm/CNC morphogenesis, and that the PCP and BMP pathways genetically interact during the morphogenetic events.</p><p><strong>Conclusions: </strong>Ultimately, our work builds on a mechanistic paradigm of ethanol-induced birth defects we have been developing, connecting the conceptual framework with concrete cellular events that could be ethanol-sensitive beyond facial development.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variations in alcohol craving and negative mood during a clinical trial of ibudilast for alcohol use disorder.","authors":"Lindsay R Meredith, Erica N Grodin, Craig K Enders, Lara A Ray","doi":"10.1111/acer.70178","DOIUrl":"https://doi.org/10.1111/acer.70178","url":null,"abstract":"<p><strong>Background: </strong>Immune medications, including ibudilast, have shown early potential in mitigating alcohol intake in preclinical models and small-scale trials for alcohol use disorder (AUD). To elucidate clinical utility and clinical mechanisms of these novel treatments, research should carefully assess medication-related changes in AUD symptomatology, including craving and negative mood, over time.</p><p><strong>Methods: </strong>This is a secondary analysis of a 12-week randomized clinical trial of ibudilast for AUD. Participants were 102 individuals (40% female, average age 44 years) seeking treatment for AUD and randomized to ibudilast (50 mg twice-daily) or matched placebo. Clinical symptom measures of alcohol craving, depression, and anxiety were collected monthly. Growth models compared rates of change in clinical symptomatology between treatment groups and tested whether changes were moderated by sex. A subsample (n = 25) completed a functional magnetic resonance imaging scan with an alcohol cue-reactivity task at week four to assess a brain-based craving marker.</p><p><strong>Results: </strong>At pretreatment, participants reported moderate craving symptoms and nonclinically elevated negative mood symptoms, on average. Participants taking ibudilast showed significantly steeper reductions in craving during the trial, as compared with placebo (1.32 vs. 0.52 points lower per month; p = 0.035). At treatment endpoint, female participants taking ibudilast reported lower craving than female participants taking placebo (p < 0.001). Greater cue-elicited brain activation in bilateral insula, bilateral orbitofrontal cortex, and right precuneus (p's < 0.02) was detected among the placebo subsample, compared to ibudilast. Rates of change for depression and anxiety did not differ between medication conditions, nor were they moderated by sex. Depression symptoms decreased during the trial, while anxiety symptoms remained relatively stable.</p><p><strong>Conclusions: </strong>Consistent with prior research, ibudilast reduced neurobiological and self-report markers of craving, with female participants showing a stronger treatment response by trial endpoint. Despite shared neuroimmune correlates between negative mood and addiction, ibudilast did not alleviate negative mood symptoms beyond placebo effects.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol-induced susceptibility to pulmonary bacterial infections: A narrative review.","authors":"Tharanja Gobalakrishnan, Prantho M Dipta, Bernard Aidoo, John Le, Samithamby Jeyaseelan","doi":"10.1111/acer.70176","DOIUrl":"https://doi.org/10.1111/acer.70176","url":null,"abstract":"<p><p>Alcohol intake is widely accepted in diverse cultures around the world, although heavy and prolonged consumption can be harmful. Alcohol influences multiple organs through interorgan and intercellular signaling cascades. The common health conditions associated with alcohol use disorder (AUD) are pancreatitis, liver cirrhosis, neuropathies, cardiomyopathies, and dementia. By virtue of its anatomical orientation and function, the lung continually encounters microbes, and this can be exacerbated by excessive alcohol consumption. Alcohol abuse is a well-known risk factor for bacterial infection in the lung. Increased susceptibility to bacterial pneumonia is caused by impaired immune responses in individuals with AUD. The key cells to defend against pulmonary infections are innate immune cells, including alveolar macrophages, neutrophils, and adaptive immune cells, such as T and B cells. This review highlights recent advances illuminating the roles of innate immune responses in bacterial pneumonia and the effects of alcohol in bacterial pneumonia. Understanding the molecular mechanisms associated with innate immunity in the lung is essential for developing effective strategies to control pneumonia and alcohol-mediated immunosuppression.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural alcohol cue reactivity as a risk factor for future drinking in youth with limited alcohol exposure.","authors":"Kathryn C Jenkins, Shiane Toleson, Alexa House, Kayla Kreutzer, K Luan Phan, Stephanie M Gorka","doi":"10.1111/acer.70152","DOIUrl":"https://doi.org/10.1111/acer.70152","url":null,"abstract":"<p><strong>Background: </strong>Heightened alcohol cue reactivity is associated with alcohol problems and poor alcohol use disorder outcomes. Theory suggests that this reflects a conditioned response, whereby cues repeatedly paired with chronic alcohol use become more salient. However, few studies have investigated the relative emergence of heightened alcohol cue reactivity. It is possible that this response occurs very early in individual drinking trajectories and may play a role in shaping future alcohol use behavior.</p><p><strong>Methods: </strong>We tested this hypothesis in a sample of youth (n = 159; ages 16-19) with limited lifetime alcohol exposure (<100 lifetime drinks). Participants completed a baseline cue reactivity task in which they viewed images of alcoholic beverages, high-calorie foods (reward control), and neutral objects. The late positive potential (LPP), measured using electroencephalography, is a positive-going event-related potential measured 400 ms after a visual cue. The LPP was used to index cue reactivity and scored as the average amplitude from parietal site Pz. At baseline and 12 months, participants completed a retrospective calendar of alcohol use. Participants were classified into groups based on lifetime alcohol exposure: (1) ≤ 10 drinks (n = 50), (2) ≤50 drinks (n = 74), (3) >50 drinks (n = 35).</p><p><strong>Results: </strong>We ran a repeated measures analysis of variance to compare the effects of task condition (alcohol cues/food cues > neutral) and drink groups on LPP amplitude. Our results revealed a significant condition × drink group interaction. Follow-up analyses revealed that, for alcohol cues only, there was a significant group effect. The highest drink exposure group exhibited greater LPP relative only to the low drink exposure group. Next, we examined whether baseline LPP to alcohol cues predicted total drinks consumed 12 months later, while controlling for baseline drinking behavior. Greater LPP to alcohol cues was associated with an increase in drinks consumed at one year.</p><p><strong>Conclusions: </strong>Heightened alcohol cue reactivity emerges with limited alcohol use and can be predictive of future drinking behaviors.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutual age-varying influences of binge drinking and cannabis use during emerging adulthood in the NCANDA cohort.","authors":"Jack T Waddell, Ty Brumback, Fiona C Baker, Shayna Cheek, Duncan B Clark, David B Goldston, Jeremy L Grove, Bonnie J Nagel, Kate B Nooner, Adolf Pfefferbaum, Kilian M Pohl, Edith V Sullivan, Susan F Tapert, Wesley K Thompson, Sandra A Brown","doi":"10.1111/acer.70139","DOIUrl":"https://doi.org/10.1111/acer.70139","url":null,"abstract":"<p><strong>Background: </strong>Binge drinking peaks during emerging adulthood and is associated with negative developmental outcomes. Within-person changes in cannabis use have been shown to coincide with binge drinking; however, whether within-person changes in binge drinking and cannabis use prospectively predict one another and whether these relations vary by age remain unknown. The current study sought to fill these gaps.</p><p><strong>Methods: </strong>Data come from National Consortium on Alcohol and Neurodevelopment (NCANDA) participants aged 18-25 years reporting alcohol and cannabis use (N = 526). Parallel-process state-trait mixed effect growth models tested whether: (1) binge drinking across emerging adulthood was correlated with cannabis use (random intercepts); (2) steeper growth in binge drinking across emerging adulthood correlated with growth in cannabis use (random slopes); and (3) age-specific, within-person changes in binge drinking/cannabis use reciprocally predicted one another.</p><p><strong>Results: </strong>Across individuals, more frequent binge drinking was correlated with more frequent concurrent cannabis use, and steeper increases in binge drinking were correlated with steeper increases in cannabis use during emerging adulthood. Within-person changes in binge drinking and cannabis use covaried. Within-person increases in cannabis use predicted subsequent increases in binge drinking between ages 18 and 21 years but decreases in binge drinking between ages 24 and 25 years. Within-person changes in binge drinking did not predict subsequent changes in cannabis use during emerging adulthood.</p><p><strong>Conclusions: </strong>Changes in cannabis use coincided with changes in binge drinking, concurrently and subsequently, particularly between ages 18 and 21 years when changes in cannabis use predicted subsequent increases in binge drinking and ages 24 and 25 years when changes in cannabis use predicted decreases in subsequent binge drinking. Incorporating motivational approaches to reduce cannabis use in alcohol interventions may be efficacious in early emerging adulthood.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The alcohol cue-exposure paradigm as a screening tool for alcohol use disorder medication development: A critical review.","authors":"Dylan E Kirsch, Erica N Grodin, Lorenzo Leggio, Sherry A McKee, Lindsay R Meredith, Ethan H Mereish, Robert Miranda, Steven J Nieto, Stephanie S O'Malley, Joseph P Schacht, Lara A Ray","doi":"10.1111/acer.70170","DOIUrl":"https://doi.org/10.1111/acer.70170","url":null,"abstract":"<p><p>The alcohol cue-exposure paradigm has a long and rich history in alcohol use disorder (AUD) research, contributing to the identification of risk factors, the recognition of craving as a core symptom, the understanding of AUD neurobiology, and the development of both pharmacological and behavioral treatments. The goal of this review was to evaluate the utility of the alcohol cue-exposure paradigm as a screening tool for AUD medication development and to provide recommendations for refinement of the paradigm. First, we review evidence supporting the predictive validity and clinical applicability of the alcohol cue-exposure paradigm. Second, we examine current practices in implementing the paradigm in AUD pharmacotherapy studies. Third, we highlight several areas for refinement and offer recommendations for the implementation of this paradigm. Finally, we outline key conclusions and actionable future directions. In summary, while the alcohol cue-exposure paradigm has an established foundation in the study of AUD pharmacotherapies, its future success hinges on a concerted effort to refine and standardize protocols and validate outcome measures in large-scale studies. Addressing these priorities could accelerate the development and regulatory approval of novel treatments for AUD.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of naltrexone prescribing for alcohol use disorder from the emergency department.","authors":"Jacob A Lebin, Colin Hensen, Zhixin Lun, Bethany K Kwan, Elizabeth M Goldberg, Ellen L Burnham, Jason A Hoppe","doi":"10.1111/acer.70145","DOIUrl":"https://doi.org/10.1111/acer.70145","url":null,"abstract":"<p><strong>Background: </strong>Excessive alcohol use is a leading cause of preventable death in the United States, with the emergency department (ED) serving as a critical touchpoint for individuals with alcohol use disorder (AUD). Despite clinical guidelines recommending initiation of medication for AUD (MAUD), such as naltrexone, ED prescribing remains rare. The objective of this study is to characterize clinician naltrexone prescribing practices for ED patients with hazardous drinking or AUD and identify patient- and encounter-level predictors of naltrexone prescribing within a large, integrated health system.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of adult ED encounters across 12 hospitals from 2022 to 2024. Eligible encounters included patients with a positive Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screen, indicating hazardous alcohol use or an active AUD, who had no exclusion criteria contraindicating naltrexone and were discharged from the ED. The primary outcome was provision of a naltrexone prescription at ED discharge, and the secondary outcome was prescription fill. We used a multivariable logistic regression model with generalized estimating equation (GEE) to identify predictors of prescribing.</p><p><strong>Results: </strong>Of 52,701 treatment-eligible ED encounters, only 0.5% resulted in a naltrexone prescription. Prescriptions were more likely in encounters involving younger, male patients with higher AUDIT-C scores, alcohol-related complaints, and those occurring at an academic ED. In the logistic GEE model, academic setting, alcohol withdrawal diagnosis, and greater alcohol misuse severity were independently associated with increased prescribing. Nearly half (45%) of ED naltrexone prescriptions were filled.</p><p><strong>Conclusions: </strong>Naltrexone prescribing among treatment-eligible patients is rare. Encouragingly, nearly half of patients receiving a prescription proceeded to fill it, highlighting a promising opportunity for ED-based prescribing of naltrexone to initiate AUD treatment. To improve AUD care, systematic ED-based strategies are urgently needed that go beyond universal screening to address barriers to MAUD initiation.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype-by-sex interaction analyses for alcohol use disorder across biobanks.","authors":"Hang Zhou, Lu Wang, Zhongzheng Mao, P J Michael Deans, Rachel L Kember, Qingyu Chen, Yasmin Zakiniaeiz, Robert Kohler, MacKenzie R Peltier, Terril L Verplaetse, Marc N Potenza, Kristen J Brennand, Amy C Justice, Henry R Kranzler, Joel Gelernter, Sherry A McKee","doi":"10.1111/acer.70173","DOIUrl":"https://doi.org/10.1111/acer.70173","url":null,"abstract":"<p><strong>Background: </strong>Alcohol use and alcohol use disorder (AUD) are significant contributors to morbidity and mortality, with different prevalences between males and females. Despite the established genetic contribution to AUD, sex as a biological variable and the interplay with genetic factors in the disorder remain largely unexplored. This study aimed to address the key question as to how genetic variations interact with biological sex to influence the AUD risk.</p><p><strong>Methods: </strong>We conducted genome-wide genotype-by-sex (G × S) interaction analyses using multiancestry datasets from the Million Veteran Program (MVP) and UK Biobank (UKB). In total, 1,039,476 participants were analyzed, comprising 150,429 AUD cases and 889,046 controls. AUD cases were defined using ICD-9/10 codes in the MVP and using ICD-10 codes (field ID 41270) along with self-reported history of alcohol addiction (field ID 20406) in the UKB.</p><p><strong>Results: </strong>In single-ancestry analyses, we identified two loci in African ancestry samples with lead single-nucleotide polymorphisms (SNPs) rs2183020 (p = 1.82 × 10^-8) and rs9304803 (p = 4.66 × 10^-8), and one locus in Admixed American ancestry samples with lead SNP rs9527196 (p = 2.83 × 10^-8). The cross-ancestry meta-analysis identified one additional locus with lead SNP rs62446539 (p = 3.95 × 10^-8). The deep learning method predicted that rs9304803 has B-cell type-specific enhancer activity. Rs2183020 and rs9304803 exhibited expression quantitative trait locus (eQTL) effects on multiple genes across various tissues, including the brain. Further experiments in ethanol-exposed human neurons confirmed expression changes in several of these genes. Phenome-wide association analyses revealed significant associations between rs2183020 and weight/body mass index, and between rs9304803 and prothrombin time (measured as international normalized ratio).</p><p><strong>Conclusions: </strong>We believe this is the first genome-wide G × S study of AUD, providing novel insights into the genetic basis of sex differences in AUD and advancing our understanding of its biological underpinnings.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal alcohol exposure increases the aggressiveness of estrogen-induced pituitary tumors in male rats.","authors":"Shaista Chaudhary, Dipak K Sarkar","doi":"10.1111/acer.70169","DOIUrl":"https://doi.org/10.1111/acer.70169","url":null,"abstract":"<p><strong>Background: </strong>We have recently shown that estrogen-induced prolactin-secreting pituitary tumors are aggressive in prenatal alcohol-exposed female rats. In this study, we investigated whether similar tumor aggressiveness occurs in estrogen-treated prenatal alcohol-exposed male rats.</p><p><strong>Methods: </strong>Pregnant Fischer 344 rats were fed from gestational days 7 and 21 with a liquid diet containing ethanol 6.7% v/v (AF), pair-fed with an isocaloric liquid diet (PF), or fed chow ad libitum (AD). Alcohol-fed dams exhibited a blood alcohol concentration of 120-150 mg/dL 2 h after the last feeding. Male offspring were orchiectomized at 60 days of age and implanted subcutaneously with estradiol implants. Four months after the estradiol implants, rats were sacrificed, and pituitary tumor tissues were collected. Tumor cells were isolated and cultured for analysis.</p><p><strong>Results: </strong>Pituitary tumor cells from AF males exhibited stem-like cell properties and showed elevated expression of stem cell regulatory genes and proteins (SOX-2, OCT-4, KLF4, SNAIL-1, and Nestin), tumor aggressiveness markers (MMP-9, CD44, CD34, PTTG, FGFR4, Ki-67, N-Cadherin), and prolactin compared to those from AD and PF controls. AF cells also had a higher cell proliferation rate, increased invasiveness, and colony formation compared to those in AD and PF cells, indicating more aggressive cancer cells than control cells. Notably, AF cells had a higher expression of developmental pluripotency-associated 4 (Dppa4), a gene we recently identified as upregulated in aggressive tumors and in fetal alcohol-exposed animals.</p><p><strong>Conclusions: </strong>These findings are consistent with our previous observations in estrogen-treated AF female rats. These results support the hypothesis that prenatal alcohol exposure programs the pituitary epithelium toward a mesenchymal stem cell-like phenotype, contributing to the development of aggressive pituitary prolactinomas in both sexes.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}