Journal of Neuroendocrinology最新文献

{"title":"The exceptionally rare phenomenon of well-differentiated colon neuroendocrine tumors.","authors":"Taymeyah Al-Toubah, Jonathan Strosberg","doi":"10.1111/jne.13491","DOIUrl":"https://doi.org/10.1111/jne.13491","url":null,"abstract":"<p><p>Colonic neuroendocrine tumors (NETs), excluding rectal NETs, are often described as relatively common and aggressive, with inferior median survival compared with other gastrointestinal (GI) primary sites. However, epidemiological databases may conflate well-differentiated NETs with poorly differentiated neuroendocrine carcinomas (NECs), leading to a lack of precise data on the prevalence, clinical behavior, and prognosis of well-differentiated colonic NETs. We analyzed a large institutional database to identify patients with well-differentiated NETs originating in the colon, excluding rectal NETs. Cecal NETs were included; however, ileocecal NETs (overlapping the ileocecal valve) were not. We assessed their prevalence compared with other primary sites, grade, stage, and prognosis. Among 3639 patients with gastroenteropancreatic (GEP) NETs, only 19 (0.5%) had well-differentiated colonic NETs. This included 11 cecal and eight sigmoid colon primaries (two described as \"rectosigmoid\"). No tumors originated in the ascending, transverse, or descending colon. Sigmoid NETs were typically early-stage polyps discovered incidentally during colonoscopy. In contrast, eight of the 11 cecal NETs metastasized (p = .04). Six of the cecal primary patients (55%) exhibited carcinoid syndrome versus none of the sigmoid primary cases (p = .01). Well-differentiated colon NETs are exceptionally rare, comprising approximately 0.5% of GEP-NETs. These tumors fall into two distinct categories: cecal NETs, which resemble ileal NETs in behavior, and sigmoid NETs, which appear similar to rectal NETs. The broad categorization of colonic \"NETs\" in epidemiologic databases likely includes NECs, obscuring the true clinical picture.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13491"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA hypomethylation-related expression of hsa-miR-184 contributes to invasive growth of gonadotroph neuroendocrine pituitary tumors.","authors":"Biniyam Tsegaye, Paulina Kober, Beata Joanna Mossakowska, Szymon Baluszek, Maria Maksymowicz, Barbara Buchalska, Jacek Kunicki, Mateusz Bujko","doi":"10.1111/jne.13492","DOIUrl":"https://doi.org/10.1111/jne.13492","url":null,"abstract":"<p><p>Gonadotroph neuroendocrine pituitary tumors are among the most common intracranial neoplasms. A notable proportion of these tumors is characterized by invasive growth which hampers the treatment results and worsens prognoses of patients. Increased hsa-miR-184 expression was observed in invasive as compared to non-invasive gonadotroph tumors. This study aimed to determine the role of hsa-miR-184 expression in invasive growth of gonadotroph tumors. QRT-PCR and bisulfite pyrosequencing were used for evaluating hsa-miR-184 expression and MIR184 DNA methylation levels, respectively, in tumors and normal pituitary samples. LβT2 and αT3-1 gonadotroph cells were used to test the effect of miR-184 on cell viability (MTT test), proliferation (BrdU incorporation), and migration (scratch assay). RNA sequencing was applied for transcriptome profiling in miR-184-treated and untreated LβT2 cells. Differential genes expression analysis combined with target prediction served for identification of miR-184 targets. MiRNA-mRNA interaction was subsequently validated with Luciferase reporter assay. Analysis of tissue samples showed that hsa-miR-184 is upregulated in gonadotroph tumors and its expression is higher in invasive than in noninvasive ones. Promoter of MIR184 is demethylated in tumors, and the methylation level is negatively correlated with hsa-miR-184 expression. Transfecting LβT2 and αT3-1 with miR-184 mimic resulted in increased cellular proliferation and viability. Differentially expressed genes were identified when comparing miR-184-treated and untreated cells, including Nus1 as the only predicted miR-184 target. The interaction between miR-184 and 3'UTR of Nus1 was confirmed in vitro in both LβT2 and αT3-1. Overexpression of Nus1 resulted in lowering cell viability in both cell lines and proliferation in LβT2. The expression level of NUS1 was lower in invasive than in noninvasive tumors. Our results indicate that DNA hypomethylation-related increase of hsa-mir-184 expression contributes to invasive growth of gonadotroph pituitary tumors through targeting NUS1, being one of the various molecular mechanisms involved in conferring aggressive growth potential.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13492"},"PeriodicalIF":3.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma adiponectin and biomarker-confirmed Alzheimer's disease in a tertiary memory clinic.","authors":"Louise Sindzingre, Elodie Bouaziz-Amar, François Mouton-Liger, Emmanuel Cognat, Julien Dumurgier, Karl Götze, Matthieu Martinet, Agathe Vrillon, Claire Paquet, Matthieu Lilamand","doi":"10.1111/jne.13493","DOIUrl":"https://doi.org/10.1111/jne.13493","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is associated with early metabolic dysfunction and adiponectin, which may play a pathophysiological role. Adiponectin is implicated in the regulation of energy homeostasis, carbohydrate, and lipid metabolism, as well as in inflammation modulation. The aim of this study was to study whether plasma adiponectin levels were different between patients with AD confirmed by biomarkers and neurological control subjects. We performed a monocentric, retrospective, cross-sectional, observational study in AD patients and neurological controls recruited from daily clinical practice in a tertiary memory clinic. Plasma adiponectin levels were measured using a chemiluminescent enzyme immunoassay. We analyzed the relationship between adiponectin and AD using linear regression models including age, gender, and BMI. We also described the distribution of adiponectin concentrations, across age, and gender categories. Two hundred and six patients (142 AD patients and 64 neurological controls) were included, with mean age = 68.8 ± 10.0 years, and 56% were women. Higher adiponectin concentrations were observed in females and in older adults. Plasma adiponectin levels were significantly higher in AD patients (mean = 6.45 ± 3.42 μg/mL) than neurological controls (4.85 ± 3.54 μg/mL) (p < .001). This association was mediated by age, gender, and BMI, which were significantly and independently associated with plasma adiponectin levels (p < .01 for each), while adiponectin was no longer associated with AD in multivariate models. Patients with AD showed higher adiponectin levels, but this association was driven by older age, female gender, and lower BMI in the AD group. Further studies are needed to better characterize the hormonal signature of AD.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13493"},"PeriodicalIF":3.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroactive steroid exposure impacts neurodevelopment: Comparison of human and rodent placental contribution.","authors":"Claire-Marie Vacher, Alex Tsompanidis, Morgan R Firestein, Anna A Penn","doi":"10.1111/jne.13489","DOIUrl":"https://doi.org/10.1111/jne.13489","url":null,"abstract":"<p><p>The placenta is a fetal endocrine organ that secretes many neuroactive factors, including steroids, that play critical roles in brain development. The study of the placenta-brain axis and the links between placental function and brain development represents an emerging research area dubbed \"neuroplacentology.\" The placenta drives many circulating fetal steroids to very high levels during gestation. Recent studies have highlighted the critical role of placental steroids in shaping specific brain structures and behaviors. This review uses a cross-species framework to discuss the genomic factors, in-utero environmental changes, and placental conditions that alter placental steroidogenesis, leading to changes in early developmental trajectories relevant for psychiatric conditions such as autism, in a sex-linked manner.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13489"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and characterisation of DOTA-kisspeptin-10 as a potential gallium-68/lutetium-177 pan-tumour radiopharmaceutical","authors":"Janke Kleynhans,&nbsp;Robert Reeve,&nbsp;Cathryn H. S. Driver,&nbsp;Biljana Marjanovic-Painter,&nbsp;Mike Sathekge,&nbsp;Jan Rijn Zeevaart,&nbsp;Thomas Ebenhan,&nbsp;Robert P. Millar","doi":"10.1111/jne.13487","DOIUrl":"10.1111/jne.13487","url":null,"abstract":"<p>Kisspeptin (KISS1) and its cognate receptor (KISS1R) are implicated in the progression of various cancers. A gallium-68 labelled kisspeptin-10 (KP10), the minimal biologically active structure, has potential as a pan-tumour radiopharmaceutical for the detection of cancers. Furthermore, a lutetium-177 labelled KP10 could find therapeutic application in treating oncological diseases. DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) was attached to the NH2-terminus of KP10 as we posited from our previous publications that this modification would not impair biological activity. Here, we showed that the biological activity, as monitored by stimulation of inositol phosphate accumulation in HEK293 transfected with the KISS1R gene, was indeed similar for KP10 and DOTA-KP10. The optimisation of radiolabelling with gallium-68 and lutetium-177 is described. Stability in serum, plasma and whole blood was also investigated. Pharmacokinetics and biodistribution were established with micro-PET/CT (positron emission tomography/computerised tomography) and ex vivo measurements. Dynamic studies with micro-PET/CT demonstrated that background clearance for the radiopharmaceutical was rapid with a blood half-life of 18 ± 3 min. DOTA-KP10 demonstrated preserved functionality at KISS1R and good blood clearance. These results lay the foundation for the further development of DOTA-KP10 analogues that have high binding affinity along with proteolytic resistance.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"37 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13487","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Capillary connections between sensory circumventricular organs and adjacent parenchyma enable local volume transmission.","authors":"Yifan Yao, Yannan Chen, Raju Tomer, Rae Silver","doi":"10.1111/jne.13490","DOIUrl":"https://doi.org/10.1111/jne.13490","url":null,"abstract":"<p><p>Among contributors to diffusible signaling are portal systems which join two capillary beds through connecting veins. Portal systems allow diffusible signals to be transported in high concentrations directly from one capillary bed to the other without dilution in the systemic circulation. Two portal systems have been identified in the brain. The first was discovered almost a century ago and connects the median eminence to the anterior pituitary gland. The second was discovered a few years ago and links the suprachiasmatic nucleus to the organum vasculosum of the lamina terminalis, a sensory circumventricular organ (CVO). Sensory CVOs bear neuronal receptors for sensing signals in the fluid milieu. They line the surface of brain ventricles and bear fenestrated capillaries thereby lacking blood-brain barriers. It is not known whether the other sensory CVOs, namely the subfornical organ (SFO), and area postrema (AP) form portal neurovascular connections with nearby parenchymal tissue. To preserve the integrity of the vasculature of CVOs and their adjacent neuropil, we combined iDISCO clearing and light-sheet microscopy to acquire volumetric images of blood vessels and traced the vasculature in two experiments. In the first, the whole brain vasculature was registered to the Allen Brain Atlas in order to identify the nuclei to which the SFO and AP are attached. In the second study, regionally specified immunolabeling was used to identify the attachment sites and vascular connections between the AP, and the SFO to their respective parenchymal attachment sites. There are venous portal pathways linking the capillary vessels of the SFO and the posterior septal nuclei, namely the septofimbrial nucleus and the triangular nucleus of the septum. Unlike the arrangement of portal vessels, the AP and the nucleus of the solitary tract share a common capillary bed. Taken together, the results reveal that all three sensory CVOs bear direct capillary connections to adjacent neuropil, providing a direct route for diffusible signals to travel from their source to their targets.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13490"},"PeriodicalIF":3.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Earlier diagnosis of small intestine neuroendocrine tumours (SI-NETs) through transformation of the South Wales NET service.","authors":"Harriet L Gould, Kapish Amin, Thanos Karategos, Sarah Abbas, Susannah Olive, Mathoorika Sivananthan, Ayeesha Rela, Harriet Reed, Catherine Powell, Janu Navaratnam, Rwth Ellis-Owen, Patrick Fielding, Dipanjali Mondal, Steve Kihara, Gethin Williams, Carys Morgan, Justyna Witczak, Julie Cornish, Sarah Gwynne, James Horwood, Jared Torkington, Rachel Hargest, Adam Christian, Michael Davies, James Ansell, Mohid S Khan","doi":"10.1111/jne.13486","DOIUrl":"https://doi.org/10.1111/jne.13486","url":null,"abstract":"<p><p>Small intestine neuroendocrine tumours (SI-NETs) are often diagnosed late with a UK median of 3 years and high misdiagnosis rates. Previous studies, largely based on patient surveys, offer little data on improving diagnosis. In 2017, the South Wales NET service underwent a nationally commissioned, systematic transformation, aiming to improve diagnosis through the development of a gastroenterology and surgical referral network, and education of these specialities. This study aims to assess the impact of the transformation on SI-NET diagnosis times and misdiagnosis rates using accurate hospital data, along with the diagnostic routes and investigations used for SI-NETs. We retrospectively analysed the hospital records of 224 patients diagnosed with SI-NETs referred to the South Wales NET service (110 pre-transformation and 114 post-transformation). Following the service transformation, there was a significant reduction in diagnosis times from a median of 12.5-5.2 months (p < .05), at an earlier stage (cases with metastases reduced from 77% to 62%), and reduced misdiagnosis rates from 40% to 25%. Colonoscopy, used to investigate the presenting gastrointestinal symptoms in 42% of patients prior to diagnosis, identified an abnormality in only 28%, compared with 97% with computed tomography (CT) scans. A gastroenterology and surgical referral network across hospitals may improve diagnosis in SI-NETs, leading to earlier detection and reducing misdiagnosis rates. Further exploration of GP interactions is needed. Caution is needed following negative colonoscopy in patients with persistent lower gastrointestinal symptoms as this could lead to missed SI-NET diagnosis if further abdominal imaging is not undertaken.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13486"},"PeriodicalIF":3.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of dyslipidemia and lipid-lowering therapy with statins in patients with neuroendocrine tumors","authors":"Antongiulio Faggiano,&nbsp;Flaminia Russo,&nbsp;Virginia Zamponi,&nbsp;Franz Sesti,&nbsp;Giulia Puliani,&nbsp;Roberta Modica,&nbsp;Pasqualino Malandrino,&nbsp;Francesco Ferraù,&nbsp;Maria Rinzivillo,&nbsp;Marco Di Muzio,&nbsp;Emanuele Di Simone,&nbsp;Nicolò Panattoni,&nbsp;Pasquale Dolce,&nbsp;Rosa Lauretta,&nbsp;Gianfranco Di Iasi,&nbsp;Antonio Prinzi,&nbsp;Ylenia Alessi,&nbsp;Tiziana Feola,&nbsp;Rossella Mazzilli,&nbsp;Marialuisa Appetecchia,&nbsp;Elisa Giannetta,&nbsp;Francesco Panzuto,&nbsp;Annamaria Colao","doi":"10.1111/jne.13485","DOIUrl":"10.1111/jne.13485","url":null,"abstract":"<p>Dyslipidemia is a potential unfavorable prognostic factor in neuroendocrine tumors (NETs); conversely, statins proved to have antiproliferative effects in NET cell lines and could be a helpful therapeutic strategy for these patients. The main objective of this observational cohort retrospective study is to explore the associations between dyslipidemia and NET progression and evaluate the potential influence of statins in this context. 393 patients with histologically confirmed gastroenteropancreatic or bronchopulmonary NETs from six Italian centres didicated to NET diagnosis and therapy were included. The cohort included 123 patients with dyslipidemia, 81 of which were taking statins. Clinicopathological data, including patient demographics, tumor characteristics, and treatment details as well as the prevalence, timing of dyslipidemia and hypolipemic therapy were collected. The main outcome measure used is progression-free survival (PFS). Among the 393 patients, 123 (31.3%) had dyslipidemia. Statins were used by 81 (65.8%) dyslipidemic patients, mostly atorvastatin. Median PFS was 87 months overall, 124 months in non-dyslipidemic patients, and 72 months in dyslipidemic patients (<i>p</i> = .268). Dyslipidemic patients on statins had a significantly better median PFS (108 months) than those not on statins (26 months; <i>p</i> = .024). Recurrence-free survival (RFS) was also evaluated, but no significant differences were found. In conclusion, while PFS was lower in dyslipidemic patients compared to non-dyslipidemic patients, the difference was not statistically significant. Statin therapy was associated with improved PFS among dyslipidemic patients, suggesting a potential antiproliferative effect of statins in NETs. These findings warrant further investigation to substantiate the role of statins in the management of NETs.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"37 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13485","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central regulation of drinking water in divergently selected high-water-efficient young broiler chickens: A minireview.","authors":"Brooklee Roach, Elizabeth S Greene, Sami Dridi","doi":"10.1111/jne.13488","DOIUrl":"https://doi.org/10.1111/jne.13488","url":null,"abstract":"<p><p>Poultry production is confronting real challenges, including a lofty projected high demand for animal proteins to feed the future, and the need to adapt to planetary boundaries (global warming) with limited natural resources (land, energy, water). Among the most challenging stressors to poultry production sustainability are heat stress (HS) and water uncertainty, that need extensive fundamental and applied research to identify effective strategies. In that regard, our group has recently developed a high-water-efficient broiler (meat-type) chicken line using water conversion ratio (WCR) as a phenotypic trait and defined the hypothalamic molecular mechanisms controlling drinking water under heat stress conditions. In response to the invitation from the Organizing Committee of the 13th International Symposium on Avian Endocrinology (ISAE 2024), the present review summarizes these data and closes the chapter by asking questions for future investigations. Data showed that HS exposure increased core body temperature (CBT) of both lines, with higher degree in HWE than in LWE counterparts. Despite this increase in CBT, HWE line drank less water but had superior performance with better feed conversion ratio (FCR) and WCR than LWE line. Molecular analyses showed that hypothalamic drinking-related neuropeptides (arginine vasopressin system, aquaporin system, renin, and angiotensin system) are affected in line- and/or environmental-dependent manner. Together, our research outcome indicates that the divergent selection for water efficiency could be an effective strategy to preserve water while maintaining optimal growth performance and could be applied to other poultry species and livestock.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13488"},"PeriodicalIF":3.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipopolysaccharide differentially alters systemic and brain glucocorticoid levels in neonatal and adult mice","authors":"Jordan E. Hamden,&nbsp;Melody Salehzadeh,&nbsp;Hitasha Bajaj,&nbsp;Michael X. Li,&nbsp;Kiran K. Soma","doi":"10.1111/jne.13481","DOIUrl":"10.1111/jne.13481","url":null,"abstract":"<p>Glucocorticoids (GCs) are secreted by the adrenal glands and increase in response to stressors (e.g., infection). The brain regulates local GC levels via GC synthesis, regeneration and/or metabolism. Little is known about local GC regulation within discrete brain regions at baseline or in response to stress. We treated male and female C57BL/6J mice at postnatal day 5 (PND5) or PND90 with lipopolysaccharide (LPS; 50 μg/kg bw i.p.) or vehicle and collected blood and brain after 4 h. We microdissected the prefrontal cortex, hippocampus, hypothalamus and amygdala. We measured seven steroids, including corticosterone, via liquid chromatography–tandem mass spectrometry and measured transcripts for key steroidogenic enzymes (<i>Cyp11b1</i>, <i>Hsd11b1</i>, <i>Hsd11b2</i>) via qPCR. At both ages, LPS increased GC levels in blood and all brain regions; however, the increases were much greater at PND90 than at PND5. Interestingly, PND5 corticosterone levels were lower in prefrontal cortex than in blood, but higher in amygdala than in blood. These changes in corticosterone levels align with local changes in steroidogenic enzyme expression, demonstrating robust regional heterogeneity and a possible mechanism for the region-specific effects of early-life stress. In contrast, PND90 corticosterone levels were lower in all brain regions than in blood and similar among regions, and steroidogenic enzyme mRNA levels were generally not affected by LPS. Together, these data indicate that local GC levels within discrete brain regions are more heterogeneous at baseline and in response to LPS at PND5 than at PND90, as a result of increased local GC production and metabolism in the neonatal brain.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"37 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}