Neuroendocrinology最新文献

{"title":"Unveiling the Prognostic Role of Synaptophysin in Conventional Colorectal Carcinomas.","authors":"Giovanna Sabella, Giovanni Centonze, Vincenzo Lagano, Andrea Scardino, Filiberto Belli, Giovanna Garzone, Carlotta Pardo, Daniela Galbiati, Sara Pusceddu, Alessandro Mangogna, Valentina Angerilli, Matteo Fassan, Andrea Vingiani, Luca Agnelli, Giancarlo Pruneri, Stefania Gobba, Silvia Uccella, Stefano La Rosa, Fausto Sessa, Carlo Capella, Massimo Milione, Massimo Milione","doi":"10.1159/000545979","DOIUrl":"10.1159/000545979","url":null,"abstract":"<p><strong>Introduction: </strong>Although neuroendocrine differentiation in colorectal carcinomas (CRCs) has been extensively reported, the biological behavior of adenocarcinomas expressing synaptophysin (Syn) but lacking typical neuroendocrine morphology remains unclear.</p><p><strong>Methods: </strong>We tested 663 conventional CRCs with non-neuroendocrine morphology for Syn expression and correlated the results with clinicopathological and molecular characteristics as well as patient survival (overall survival [OS] and disease-free survival [DFS]). The survival characteristics of Syn expression group were compared to those of conventional CRCs and subsequently to those of 14 minENs.</p><p><strong>Results: </strong>Syn immunohistochemical expression ≥30% was confirmed in 27 (4.1%) patients and correlated with right colon site, grade 2, marked intratumoral lymphocyte infiltrate, and BRAF p.V600E mutation. At univariate analysis, variables associated with poor OS were 10-year increase in age (p = 0.001), stage III-IV (p = 0.001), Syn ≥30% (p = 0.001), infiltrative growth (p = 0.04), and residual tumor R1-2 (p = 0.03). At multivariable analysis, Syn expression in ≥30% of gland-forming tumor cells emerged as an independent negative prognostic factor for both OS and DFS. Moreover, 10-year increase in age, stage III-IV, and Syn ≥30% (p < 0.001) were associated with poor OS and marked peritumoral lymphocyte infiltrate with longer OS (p = 0.02). Comparable results were obtained according to DFS; in addition, right colon site (p = 0.04) was associated with longer DFS while KRAS mutation (p = 0.04) was associated with poor DFS at univariate analysis. MiNEN patients showed a shorter DFS than all conventional adenocarcinomas with or without Syn expression in univariate analyses (p < 0.001).</p><p><strong>Conclusions: </strong>Among conventional CRCs, we provided evidence that Syn expression is associated with worse OS and DFS and contributes to predicting clinical outcome. Future studies should explore the molecular mechanisms underlying the acquisition of the neuroendocrine phenotype to identify new targeted treatment strategies.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"632-647"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12233971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Drug Treatments for Male Patients with Prolactinomas.","authors":"Da Peng Wang, Han Yang Zhou, Yan Zhang, Li Xue, Zhe Bao Wu","doi":"10.1159/000546443","DOIUrl":"10.1159/000546443","url":null,"abstract":"<p><strong>Background: </strong>Pituitary adenomas (PAs), the most common intracranial neuroendocrine tumors, are typically benign. Among them, prolactinomas - tumors that secrete prolactin - account for approximately 60% of all PAs and are characterized by hyperprolactinemia and potential mass effects. Significant epidemiological and clinical differences exist between male and female prolactinoma patients.</p><p><strong>Summary: </strong>Prolactinomas in male patients tend to be larger and more aggressive, presenting unique challenges in treatment and management. Although dopamine agonists (DAs) remain the first-line therapy, men exhibit higher rates of DA resistance compared to women. For refractory prolactinomas in males, alternative treatments include temozolomide (TMZ), immune checkpoint inhibitors (anti-PD-1/PD-L1 and anti-CTLA4), somatostatin receptor analogs, mTOR inhibitors, tyrosine kinase inhibitors, bevacizumab, and aromatase inhibitors. These therapies may provide greater benefits to men with refractory prolactinomas than to women.</p><p><strong>Key messages: </strong>Despite advancements, significant challenges and opportunities persist in managing male prolactinoma patients. Key areas requiring attention include early diagnosis, predicting drug responsiveness, understanding sex-specific molecular mechanisms, and developing novel therapeutic strategies. Large-scale clinical trials are crucial to further assess the efficacy and safety of these treatments in men. This review consolidates recent progress in medical therapies and management approaches for male prolactinoma patients.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"657-677"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of DAXX/ATRX Protein Expression Results in Ischemia Resistance and Radiation Sensitivity in Pancreatic Neuroendocrine Tumor Cells and Is Associated with Improved Response to Trans-Arterial Radioembolization.","authors":"Caleb Solivio, Gavin Yuan, Anthony J Rizzo, Mindy K Graham, Larissa Shenker, Will Vista, Adam Gil, Himanshu Singh, Erica Alexander, Adrian Gonzalez-Aguirre, Jonathan Latzman, E Nadia Petre, Hooman Yarmohammadi, Joseph P Erinjeri, Anne Covey, Eric Chan, James Russell, Lisa Bodei, Nitya Raj, Diane Reidy-Lagunes, Christopher M Heaphy, Etay Ziv","doi":"10.1159/000547041","DOIUrl":"10.1159/000547041","url":null,"abstract":"<p><strong>Introduction: </strong>Metastatic liver pancreatic neuroendocrine tumors (PNETs) can be treated with ischemia-based trans-arterial embolization/trans-arterial chemo-embolization or radiation-based trans-arterial radioembolization (TARE). Guidelines for treatment selection are limited. The purpose of this study was to measure the effect of loss of DAXX/ATRX protein expression on ischemia and radiation sensitivity in Bon-1 and QGP-1 cells, and to compare TARE response in PNETs with and without a DAXX/ATRX mutation.</p><p><strong>Methods: </strong>This was a laboratory investigation and retrospective review of an institutional database of TARE-treated PNET patients. Ischemia and radiation sensitivity were tested on Bon-1 and QGP-1 cells and CRISPR-generated DAXX (C16/C45) and ATRX (QAX12/QAX24) knockouts. Post-ischemia and postradiation cell viability, survival fraction, and caspase-3 expression were measured. Local progression-free survival (LPFS) was measured from time of TARE to local progression or death and estimated using Cox proportional hazards.</p><p><strong>Results: </strong>Post-ischemia DAXX (C16/C45) and ATRX (QAX12/QAX24) knockouts had increased cell viability compared with Bon-1 wild-type cells (p < 0.0001, days 3, 5) and QGP-1 wild-type cells (p < 0.0001, days 3, 5, 7). Postradiation C16/C45 and QAX12/QAX24 had decreased survival fraction compared with respective wild type (p < 0.0001, all cell lines). C16/C45 had decreased apoptotic activity post-ischemia and increased apoptotic activity postradiation compared with wild type (p < 0.0001, all cell lines). Presence of DAXX/ATRX mutation was associated with longer LPFS after TARE (p < 0.001). Median LPFS after TARE was 6 months in wild type compared with 22 months in patients with DAXX/ATRX mutation.</p><p><strong>Conclusion: </strong>Loss of DAXX/ATRX protein expression is associated with ischemia resistance and radiation sensitivity in Bon-1 and QGP-1 cells and longer LPFS after TARE in PNET patients.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"730-740"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic Cancer Hallmarks as Novel Markers Associated with Progression-free Survival in Gastroenteropancreatic Neuroendocrine Tumor Patients Undergoing PRRT.","authors":"Mahesh Kumar Padwal, Rahul Vithalrao Parghane, Avik Chakraborty, Aman Kumar Ujaoney, Narasimha Anaganti, Sandip Basu, Bhakti Basu","doi":"10.1159/000542918","DOIUrl":"https://doi.org/10.1159/000542918","url":null,"abstract":"<p><strong>Introduction: </strong>Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors often detected at the metastatic stage. The aim of this study was to profile the peripheral blood transcriptome through RNA-Seq and investigate the association of the systemic cancer hallmarks with progression-free survival in PRRT-treated GEP-NET patients.</p><p><strong>Methods: </strong>The cohorts were: discovery cohort [PRRT-naïve well-differentiated GEP-NETs, n=59; age- and sex-matched healthy individuals, n=38], and independent evaluation cohort [GEP-NETs, n=66]. Peripheral blood transcriptomes were profiled through RNA sequencing and cancer hallmarks were identified via Gene Set Enrichment Analysis (GSEA). Activities of cancer hallmarks in each sample were calculated using Gene Set Variation Analysis (GSVA). Differentially expressed genes were identified with DESeq2. Progression-free survival was used as a primary endpoint and prognostic association was evaluated using univariate and multivariate COXPH analyses.</p><p><strong>Results: </strong>RNA-Seq captured global changes in the peripheral blood transcriptome of GEP-NET patients. Peripheral blood transcriptome of NET patients showed differential enrichment of 30 systemic cancer hallmarks viz., TNF-α signaling via NF-κB, IL2/STAT5 signaling, TNF-α response, TNF-γ response, IL6/JAK/STAT signaling, TGF-β signaling, heme metabolism. etc. In the univariate analyses, two cancer hallmarks were prognostically significant (p<0.05) in GEP-NETs. Heme metabolism and IL2/STAT5 signaling were statistically significant in the Discovery cohort (n=58) and independent evaluation cohort (n=66). In multivariate COXPH analyses, heme metabolism and IL2/STAT5 signaling were independently associated with PFS in GEP-NET patients undergoing PRRT.</p><p><strong>Conclusions: </strong>This study provides comprehensive coverage of the peripheral blood transcriptome of GEP-NET patients via RNA-Seq and identifies systemic cancer hallmarks as independent prognostic factors in NETs.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-18"},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid hormone clearance in the paraventricular nucleus of male mice regulates lean mass and physical activity.","authors":"Zhaofei Wu,Arturo Hernandez","doi":"10.1159/000541525","DOIUrl":"https://doi.org/10.1159/000541525","url":null,"abstract":"INTRODUCTIONThe actions of thyroid hormones (THs) in the central nervous system (CNS) are relevant to food intake and energy expenditure. TH receptors (TRs) exhibit high expression in brain areas modulating energy balance, including the arcuate, paraventricular (PVN), supraoptic, and ventromedial (VMH) hypothalamic nuclei.METHODSTo examine the role of THs in the regulation of energy balance via action in specific hypothalamic nuclei of the adult mouse, we performed experiments of conditional inactivation of DIO3, the enzyme responsible for the clearance of THs, in the lateral hypothalamus (LH), and VMH and PVN hypothalamic nuclei. We accomplished DIO3 genetic inactivation via stereotaxic injection of the AAV-cre vector into adult mice homozygous for a \"floxed\" Dio3 allele.RESULTSDio3 inactivation in the LH and VMH of males or females did not result in significant changes in body weight 8-weeks after injection. However, inactivation of Dio3 in the PVN resulted in increased body weight (both fat mass and lean mass) and locomotor activity, and decreased hypothalamic Mc4r expression in male, but not female mice. However, PNV-specific Dio3 KO did not cause hyperphagia.CONCLUSIONThese results suggest local TH action influences MC4R signaling and possibly other PVN-associated circuitries, with consequences for body composition and energy balance endpoints, but not for orexigenic pathways. They also support a regulatory role for PVN Dio3 in the central regulation of energy homeostasis in adult life.","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":"53 1","pages":"1-18"},"PeriodicalIF":4.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Relationships between Gut Microbiotas, Blood Metabolites, and Neuroendocrine Tumors: A Mediated Mendelian Randomization Study.","authors":"ZheXu Cao,JiangSheng Huang,Xia Long","doi":"10.1159/000541298","DOIUrl":"https://doi.org/10.1159/000541298","url":null,"abstract":"Introduction Neuroendocrine tumors (NETs) are a heterogeneous group of epithelial tumors originating from different anatomical sites, identifying the gut microbiota and metabolic mechanisms involved in the onset of NETs may help to develop appropriate disease prevention and monitoring strategies. Methods We employed a mediated two-sample Mendelian Randomization (MR) approach, analyzing gut microbiota from German studies and NET datasets from the 10th round of the FinnGen project. Mediation analyses were conducted using the metabolites dataset from the Canadian Longitudinal Study of Aging (CLSA) and the TwinsUK study. Instrumental variables (IVs) chosen according to established MR criteria and analyzed using the Wald ratio, inverse-variance weighted (IVW), MR-Egger, and weighted median methods. To ensure robustness, sensitivity analyses were performed using Cochrane's Q, Egger's intercept, MR-PRESSO, and leave-one-out (LOO) methods. Results Causal relationships were identified between the genetic determinants of 6, 5, 2, 1, 2, 3 gut microbiotas and the risk of colorectal, lung, pancreatic, rectum, small intestine and stomach NETs. Similarly, the genetic determinants of 4, 6, 1, 5, 10 and 7 metabolites were found to be causally related to the risk of colorectal, lung, pancreatic, rectum, small intestine and stomach NETs, respectively. Through Wald ratio and IVW methods, we preliminarily identified 957 microbiota-metabolite pairs with significant causal associations, and formed 13 mediated relationships between the impact of gut microbiotas on NETs. Conclusion Our study suggests that gut microbiotas and its derived metabolites may contribute to the onset of NET, offering a novel insight into the disease's pathogenesis.","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":"1 1","pages":"1-17"},"PeriodicalIF":4.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prelims.","authors":"","doi":"10.1159/000541089","DOIUrl":"https://doi.org/10.1159/000541089","url":null,"abstract":"","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":"114 9","pages":"799-802"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Insulin Levels Engage the Salience Network during Multisensory Perception.","authors":"Katja Schumann, Rea Rodriguez-Raecke, Rik Sijben, Jessica Freiherr","doi":"10.1159/000533663","DOIUrl":"10.1159/000533663","url":null,"abstract":"<p><strong>Introduction: </strong>Brain insulin reactivity has been reported in connection with systematic energy metabolism, enhancement in cognition, olfactory sensitivity, and neuroendocrine circuits. High receptor densities exist in regions important for sensory processing. The main aim of the study was to examine whether intranasal insulin would modulate the activity of areas in charge of olfactory-visual integration.</p><p><strong>Methods: </strong>As approach, a placebo-controlled double-blind within crossover design was chosen. The experiments were conducted in a research unit of a university hospital. On separate mornings, twenty-six healthy normal-weight males aged between 19 and 31 years received either 40 IU intranasal insulin or placebo vehicle. Subsequently, they underwent 65 min of functional magnetic resonance imaging whilst performing an odor identification task. Functional brain activations of olfactory, visual, and multisensory integration as well as insulin versus placebo were assessed. Regarding the odor identification task, reaction time, accuracy, pleasantness, and intensity measurements were taken to examine the role of integration and treatment. Blood samples were drawn to control for peripheral hormone concentrations.</p><p><strong>Results: </strong>Intranasal insulin administration during olfactory-visual stimulation revealed strong bilateral engagement of frontoinsular cortices, anterior cingulate, prefrontal cortex, mediodorsal thalamus, striatal, and hippocampal regions (p ≤ 0.001 familywise error [FWE] corrected). In addition, the integration contrast showed increased activity in left intraparietal sulcus, left inferior frontal gyrus, left superior frontal gyrus, and left middle frontal gyrus (p ≤ 0.013 FWE corrected).</p><p><strong>Conclusions: </strong>Intranasal insulin application in lean men led to enhanced activation in multisensory olfactory-visual integration sites and salience hubs which indicates stimuli valuation modulation. This effect can serve as a basis for understanding the connection of intracerebral insulin and olfactory-visual processing.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"90-106"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10439133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapagliflozin Ameliorates Ovulation Disorders via Attenuating Activated Microglia-Mediated Hypothalamic Inflammation in HFD-Fed Mice.","authors":"Xiaolin Chen, Zhuoni Xiao, Qing Liu, Deng Luo, Yuli Cai, Mingxia Fan","doi":"10.1159/000535420","DOIUrl":"10.1159/000535420","url":null,"abstract":"<p><strong>Introduction: </strong>Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown neuroprotective effects in obese mice. However, whether SGLT2i can ameliorate high-fat diet (HFD)-related ovulation disorders remains unknown. The aim of this research was to investigate whether dapagliflozin improves HFD-induced ovulatory dysfunction by attenuating microglia-mediated hypothalamic inflammation.</p><p><strong>Methods: </strong>C57BL/6J female mice fed HFD were treated with dapagliflozin (1 mg/kg) for 22 weeks. Plasma insulin, leptin, luteinizing hormone (LH), estradiol (E2), and IL-1β levels were also tested. Microglial morphology, cell numbers, and SGLT2 expression were evaluated using immunofluorescence. The expression of IL-1β, NLRP3, kisspeptin, gonadotropin-releasing hormone (GnRH), SGLT2, insulin, and leptin receptors in the hypothalamus was determined using immunohistochemical staining. We also examined the effects of dapagliflozin on glucose metabolism and the release of inflammatory factor in palmitic acid (PA)-treated HMC3 cells.</p><p><strong>Results: </strong>As expected, dapagliflozin improved HFD-induced metabolic disturbances, peripheral versus central insulin and leptin resistance and also restored the regular estrous cycle. Furthermore, dapagliflozin blunted microglia activation, NLRP3 inflammasome priming, hypothalamic inflammation, and increased the expression of GnRH and kisspeptin at proestrus in the hypothalamus. Additionally, dapagliflozin markedly reduced IL-6 and NO release and fat accumulation, decreased lactic acid production and glucose consumption, and inhibited mammalian target of rapamycin (mTOR) and hexokinase 2 (HK2) expression in PA-treated HMC3 cells. These effects suggest that dapagliflozin reduced the mTOR/HK2-mediated aerobic glycolysis.</p><p><strong>Conclusions: </strong>Dapagliflozin improved HFD-related ovulation disorders by regulating glucose metabolism through mTOR/HK2 signaling and attenuating microglia-mediated hypothalamic inflammation. These results validate the novel role for the neuroprotection of SGLT2i in HFD-induced obesity and ovulation disorders.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"331-347"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in Serum miR-126-3p Levels over Time: A Marker of Pituitary Insufficiency following Head Trauma.","authors":"Esra Tufan, Serpil Taheri, Züleyha Karaca, Ecmel Mehmetbeyoglu, Zeynep Yilmaz Sukranli, Kezban Korkmaz Bayram, Halil Ulutabanca, Fatih Tanrıverdi, Kursad Unluhizarci, Minoo Rassoulzadegan, Fahrettin Kelestimur","doi":"10.1159/000535748","DOIUrl":"10.1159/000535748","url":null,"abstract":"<p><strong>Introduction: </strong>Traumatic brain injuries (TBIs) pose a high risk of pituitary insufficiency development in patients. We have previously reported alterations in miR-126-3p levels in sera from patients with TBI-induced pituitary deficiency.</p><p><strong>Methods: </strong>To investigate why TBI-induced pituitary deficiency develops only in some patients and to reveal the relationship between miR-126-3p with hormone axes, we used mice that were epigenetically modified with miR-126-3p at the embryonic stage. These modified mice were subjected to mild TBI (mTBI) according to the Marmarou's weight-drop model at 2 months of age. The levels of miR-126-3p were assessed at 1 and 30 days in serum after mTBI. Changes in miR-126-3p levels after mTBI of wild-type and miR-126-3p* modified mouse lines validated our human results. Additionally, hypothalamus, pituitary, and adrenal tissues were analyzed for transcripts and associated serum hormone levels.</p><p><strong>Results: </strong>We report that miR-126-3p directly affects hypothalamus-pituitary-adrenal (HPA) axis upregulation and ACTH secretion in the acute phase after mTBI. We also demonstrated that miR-126-3p suppresses Gnrh transcripts in the hypothalamus and pituitary, but this is not reflected in serum FSH/LH levels. The increase in ACTH levels in the acute phase may indicate that upregulation of miR-126-3p at the embryonic stage has a protective effect on the HPA axis after TBI. Notably, the most prominent transcriptional response is found in the adrenals, highlighting their role in the pathophysiology of TBI.</p><p><strong>Conclusion: </strong>Our study revealed the role of miR-126-3p in TBI and pituitary deficiency developing after TBI, and the obtained data will significantly contribute to elucidating the mechanism of pituitary deficiency development after TBI and development of new diagnostic and treatment strategies.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"315-330"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138808235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}