Neuroendocrinology最新文献

{"title":"Nociceptin-Opioid-Related Nociceptin Receptor 1 Signaling Partly Mediates Glucoprivic Suppression of Luteinizing Hormone Pulses in Female Rats: Arcuate <italic>Kiss1</italic> Neurons as a Possible Target for Nociceptin.","authors":"Marina Takizawa, Koki Yamada, Mayuko Nagae, Shunsuke Seki, Sena Matsuzaki, Masumi Hirabayashi, Naoko Inoue, Yoshihisa Uenoyama, Hiroko Tsukamura","doi":"10.1159/000546766","DOIUrl":"10.1159/000546766","url":null,"abstract":"<p><strong>Introduction: </strong>During malnutrition, mammalian reproductive functions are suppressed by inhibition of the pulsatile release of gonadotropin-releasing hormone (GnRH)/gonadotropins. This study aimed to investigate whether nociceptin-opioid-related nociceptin receptor 1 (OPRL1) signaling mediates glucoprivic suppression of luteinizing hormone (LH) pulses in female rats.</p><p><strong>Methods and results: </strong>RNA sequencing analysis of tdTomato-positive arcuate (ARC) kisspeptin neurons obtained from Kiss1 (kisspeptin gene)-Cre/Cre-dependent tdTomato reporter female rats showed that Oprl1 messenger RNA expression was evident in ARC kisspeptin neurons. Double in situ hybridization for Kiss1 and Oprl1 or prepronociceptin gene (Pnoc) revealed that approximately 20% of Kiss1-expressing cells co-expressed Oprl1, but not Pnoc in ovariectomized (OVX) wild-type rats treated with diestrus levels of estradiol-17β (low E2). Administration of [N-Phe1]-orphanin FQ (1-13) amide (NC13), a selective OPRL1 antagonist, to the third ventricle (3V) transiently reversed the suppression of LH pulses induced by intravenous (iv) 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, in OVX + low E2 rats. The frequency of LH pulses during the first hour of the 3-h sampling period was significantly higher in 3V NC13-treated rats than in vehicle-treated controls. In contrast, 3V NC13 administration failed to affect LH pulses in OVX + low E2 rats without iv 2DG treatment. Furthermore, iv 2DG treatment significantly increased the percentage of fos-positive ARC Pnoc-expressing cells in OVX + low E2 rats.</p><p><strong>Conclusion: </strong>These results indicate that ARC nociceptin-OPRL1 signaling partly mediates the glucoprivic suppression of LH pulses and that nociceptin may directly suppress ARC kisspeptin neurons, the GnRH/LH pulse generator in female rats.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"689-703"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302574","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":"Upregulation of SSTR2 Expression and Radioligand Binding of [18F]SiTATE in Neuroendocrine Tumour Cells with Combined Inhibition of Class I HDACs and LSD1.","authors":"Christoph J Auernhammer, Kathrin Zitzmann, Simon Lindner, Harun Ilhan, Peter Bartenstein, Umberto Maccio, Michael Orth, Lea Peischer, Julian Maurer, Gerald Spoettl, Katharina Wang, Christine Spitzweg, Alessa Fischer, Constanze Hantel, Ashley B Grossman, Felix Beuschlein, Karel Pacak, Svenja Nölting","doi":"10.1159/000545073","DOIUrl":"10.1159/000545073","url":null,"abstract":"<p><strong>Introduction: </strong>Peptide receptor radionuclide therapy (PRRT) is a highly effective, targeted treatment option in advanced neuroendocrine tumours (NETs). However, NET patients expressing low levels of Somatostatin receptor type (SSTR) 2 do not benefit from this powerful tool. Recently, several preclinical studies have revealed that histone deacetylase (HDAC) inhibitors can upregulate the expression of SSTR2 and enhance somatostatin ligand binding to tumour cells. In this preclinical study, we explored the effects of single and combined treatment of NET cells with the class I HDAC inhibitor entinostat and the lysine-specific demethylase 1 (LSD1) inhibitor CC-90011, on cell viability, SSTR2 expression and radioligand binding.</p><p><strong>Methods: </strong>The human NET cell lines BON1, NCI-H727, and QGP1 were treated with entinostat, CC-90011 or a combination of both. Cell viability was measured with a cell viability assay. SSTR2 expression was assessed by quantitative PCR, Western blot analysis, and immunohistochemistry. [18F]SiTATE uptake was investigated by a radioligand binding assay.</p><p><strong>Results: </strong>Treatment of NET cells with entinostat, CC-90011, and especially the combination of both reduced tumour cell viability and strongly induced SSTR2 expression resulting in potently enhanced radioligand binding of [18F]SiTATE.</p><p><strong>Conclusion: </strong>Combined inhibition of class I HDACs and LSD1 potently increases SSTR2 expression and consequently radioligand binding and might thus be a putative strategy to improve the outcome of PRRT therapy in patients with NETs.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"618-631"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795853","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":"Sensorimotor Development in Rat Neonates Exposed to 17-α-Hydroxyprogesterone Caproate: A Progestin Used in Obstetrics.","authors":"Paige L Graney, Evelyn L Sarno, Jessie E Miller, Christine K Wagner","doi":"10.1159/000546356","DOIUrl":"10.1159/000546356","url":null,"abstract":"<p><strong>Introduction: </strong>17-α-hydroxyprogesterone caproate (17-OHPC) is prescribed to pregnant individuals at risk for preterm birth during critical periods of fetal cortical maturation. Yet the potential long-term effects of 17-OHPC on neural and behavioral development in children are unknown. Nuclear progesterone receptor (PR) is expressed in all functional regions of rat cortex during development. The hypothesis that developmental exposure to 17-OHPC alters sensorimotor development was tested.</p><p><strong>Methods: </strong>Sensorimotor behaviors were observed in neonates administered 17-OHPC from the day of birth through postnatal day 11, and PR was quantified in cortex at P11.</p><p><strong>Results: </strong>17-OHPC administration resulted in a disruption in sensorimotor indicators of typical brain development, without affecting gross motor function. 17-OHPC-exposed rats had significantly fewer PR-immunoreactive nuclei in somatosensory cortex.</p><p><strong>Conclusions: </strong>These findings demonstrate that 17-OHPC exposure during critical periods of cortical development may impact sensorimotor development and cortical sensitivity to progestins, highlighting the need for further investigation on the clinical implications of this progestin.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"678-688"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120307","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":"Gender Differences in Lung Neuroendocrine Tumors: A Single-Center Experience.","authors":"Alessia Liccardi, Annamaria Colao, Roberta Modica","doi":"10.1159/000539412","DOIUrl":"10.1159/000539412","url":null,"abstract":"<p><strong>Introduction: </strong>Gender difference may affect lung neuroendocrine tumor (L-NET) onset, progression, and outcomes as emerged in other cancers. This study aimed to analyze gender difference in L-NET to identify potential prognostic factors, to improve patient follow-up and therapeutic strategies.</p><p><strong>Methods: </strong>Patients with histologically confirmed L-NEN diagnosis referred to the ENETS CoE of the Endocrinology Unit, Federico II University of Naples, from 2013 to 2023, were retrospectively evaluated.</p><p><strong>Results: </strong>Among 48 patients with L-NEN, 38 (79.2%) with sporadic L-NET were enrolled: 22 typical (57.9%) and 16 atypical (42.1%) carcinoids, 22 (57.9%) female and 16 (42.1%) male, mean age at diagnosis 57.3 years (range 16-84). Median follow-up was 70.5 months (range 12-305). No statistical difference resulted regarding smoking habit, BMI, primary site (left/right and central/peripheral), and histological characteristics, between cohorts. Metastasis at diagnosis was found in 20 patients (52.3%), 10 female (10%) and 10 male (10%) (p: 0.20). Progressive disease (PD) was observed in 14 (36.8%) patients, and male sex developed PD more frequently 9/14 (64.3%) than female 5 (35.7%), p: 0.05. Male sex seemed to show more frequently bone metastasis without reaching statistical difference, 7 male/10 (70%), p: 0.06. Among 9 deaths (23.7%), 7 (77.8%) were men and 7 died for PD, p < 0.03. Male had a poorer prognosis than female regarding progression-free survival (PFS) (p: 0.04) and overall survival (p: 0.001), also when sub-groups of patient metastatic at diagnosis were compared (p: 0.02 and p: 0.02).</p><p><strong>Conclusions: </strong>This study showed a worse prognosis in male than female with L-NET, despite similar clinical features, tumor type, stage, and treatment, with regard to PFS, OS, and metastatic spread. These findings may suggest a closer follow-up in men, with potential positive impact on outcomes.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"371-380"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087803","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":"The Effect of Metformin on Prolactin Concentration in Women with Hyperprolactinemia and Subclinical Hyperthyroidism.","authors":"Robert Krysiak, Karolina Kowalcze, Bogusław Okopień","doi":"10.1159/000545525","DOIUrl":"10.1159/000545525","url":null,"abstract":"<p><strong>Introduction: </strong>Because prolactin excess and hyperthyroidism are often complicated by hyperglycemia and impaired insulin sensitivity, many patients with both these disorders are treated with metformin. This drug inhibits secretory function of overactive anterior pituitary cells, including lactotrophs. The purpose of the current study was to investigate whether metformin action on prolactin oversecretion is impacted by coexisting hyperthyroidism.</p><p><strong>Methods: </strong>Our prospective, cohort study included two groups of women in reproductive age requiring metformin therapy with mild or moderate hyperprolactinemia. Patients with concomitant grade 1 subclinical hyperthyroidism (group A) and individuals without thyroid pathology (group B) were matched for age, insulin sensitivity, and total prolactin levels. Glucose homeostasis markers, thyroid-stimulating hormone (TSH), free thyroid hormones, total and monomeric prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, adrenocorticotropic hormone, IGF-1, and peripheral markers of thyroid hormone action (ferritin and osteocalcin) were measured before and after 6-month metformin therapy.</p><p><strong>Results: </strong>At baseline, both groups differed in levels of TSH, free thyroid hormones, ferritin, and osteocalcin. Although metformin reduced glucose, improved insulin sensitivity and reduced total and monomeric prolactin in both groups, these effects were more pronounced in group A than group B. The impact on prolactin in group A correlated with concentrations of free thyroid hormones. Only in group A, did metformin slightly increase FSH and LH concentrations. In women with hyperthyroidism and without thyroid pathology, there were no statistical differences between baseline and follow-up levels of the remaining variables.</p><p><strong>Conclusion: </strong>The study results suggest that hyperthyroidism potentiates the impact of metformin on secretory function of overactive lactotrophs in reproductive-age women.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"553-563"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753696","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":"Special Issue Advancements and Challenges in Neuroendocrine Tumor Research.","authors":"Patricia Borges de Souza, Massimiliano Mazza","doi":"10.1159/000545920","DOIUrl":"10.1159/000545920","url":null,"abstract":"","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"361-363"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036627","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":"Acquiring Social Safety Engages Oxytocin Neurons in the Supraoptic Nucleus: Role of Magel2 Deficiency.","authors":"Prabahan Chakraborty, Hugo Lamat, Emilie M André, Pierre Fontanaud, Freddy Jeanneteau","doi":"10.1159/000538437","DOIUrl":"10.1159/000538437","url":null,"abstract":"<p><strong>Introduction: </strong>Exposure to social trauma may alter engagement with both fear-related and unrelated social stimuli long after. Intriguingly, how simultaneous discrimination of social fear and safety is affected in neurodevelopmental conditions remains underexplored. The role of the neuropeptide oxytocin is established in social behaviors and yet unexplored during such a challenge post-social trauma.</p><p><strong>Methods: </strong>Using Magel2 knockout mice, an animal model of Prader-Willi syndrome (PWS) and Schaaf-Yang syndrome (SYS), we tested memory of social fear and safety after a modified social fear conditioning task. Additionally, we tracked the activity of oxytocin neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus by fiber photometry, as animals were simultaneously presented with a choice between fear and safe social cue during recall.</p><p><strong>Results: </strong>Male Magel2 KO mice trained to fear females with electrical footshocks avoided both unfamiliar females and males during recalls, lasting even a week post-conditioning. On the contrary, trained Magel2 WT avoided only females during recalls, lasting days rather than a week post-conditioning. Inability to overcome social fear and avoidance of social safety in Magel2 KO mice were associated with the reduced engagement of oxytocin neurons in the SON but not the PVN.</p><p><strong>Conclusion: </strong>In a preclinical model of PWS/SYS, we demonstrated region-specific deficit in oxytocin neuron activity associated with behavioral generalization of social fear to social safety. Insights from this study add to our understanding of oxytocin action in the brain at the intersection of social trauma and PWS/SYS.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"138-153"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867781","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":"Comparative Targeted Genome Profiling between Solid and Liquid Biopsies in Gastroenteropancreatic Neuroendocrine Neoplasms: A Proof-of-Concept Pilot Study.","authors":"Irene Gagliardi, Federica Campolo, Patricia Borges de Souza, Lucrezia Rossi, Manuela Albertelli, Federica Grillo, Luigi Caputi, Massimiliano Mazza, Antongiulio Faggiano, Maria Chiara Zatelli","doi":"10.1159/000541346","DOIUrl":"10.1159/000541346","url":null,"abstract":"<p><strong>Introduction: </strong>Clinical presentation and genetic profile of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly variable, hampering their management. Sequencing of circulating tumor DNA from liquid biopsy (LB) has been proposed as a less invasive alternative to solid biopsy (SB). Our aim was to compare the mutational profile (MP) provided by LB with that deriving from SB in GEP-NETs.</p><p><strong>Methods: </strong>SB and LB were derived simultaneously from 6 GEP-NET patients. A comparative targeted next-generation sequencing (NGS) analysis was performed on DNA from SB and LB to evaluate the mutational status of 11 genes (MEN1, DAXX, ATRX, MUTYH, SETD2, DEPDC5, TSC2, ARID1A, CHECK2, MTOR, and PTEN).</p><p><strong>Results: </strong>Patients (M:F = 2:1; median age 64 years) included 3 with pancreatic and 3 with ileal NETs. NGS detected a median number of 55 variants/sample in SB and 66.5 variants/sample in LB specimens (mutational burden: 0.2-1.9 and 0.3-1.8 mut/Mb, respectively). Missense and nonsense mutations were prevalent in both, mainly represented by C>T transitions. ARID1A, MTOR, and ATRX were consistently mutated in SB, and ARID1A, TSC2, MEN1, PTEN, SETD2, and MUTYH were consistently mutated in LB. DAXX mutations were absent in LB. Seventeen recurrent mutations were shared between SB and LB; in particular, MTOR single-nucleotide variants c.G4731A and c.C2997T were shared by 5 out of 6 patients. Hierarchical clustering supported genetic similarity between SB and LB.</p><p><strong>Conclusions: </strong>This pilot study explores the applicability of LB in GEP-NET MP evaluation. Further studies with larger cohorts are needed to validate LB and to define the clinical impact.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"422-433"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504780","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":"Effect of Thyroid Status Modulation on Pituitary and Peripheral Hormone Concentrations in Healthy Older Subjects.","authors":"Evie van der Spoel, Saskia Cornet, Ana Zutinic, Bart Ballieux, P Eline Slagboom, Hanno Pijl, Diana van Heemst","doi":"10.1159/000542832","DOIUrl":"10.1159/000542832","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Depending on age, sex, and familial longevity, alterations in thyroid status occur frequently and often co-occur with differences in other hormonal axes. However, studies that explore the effects of thyroid status modulation on other hormonal axes remain scarce. We aimed to determine the effects of thyroid status modulation on prolactin, IGF-1, cortisol, LH, testosterone, and SHBG levels. We also explored whether effects differed depending on type of challenge, sex, and familial longevity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data were gathered from two single-arm challenge studies comprising an intramuscular injection of 0.1 mg recombinant human TSH (rhTSH, N = 29) or 100 µg T3 orally (N = 27) in healthy older individuals. Changes in hormone concentration profiles relative to baseline were determined for 4 and 5 days, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;IGF-1 increased with a maximum of 6.3% (SEM = 1.6%, p = 0.002) in the rhTSH challenge and 8.8% (SEM = 1.6%, p &lt; 0.001) in the T3 challenge, while LH (19.3% [SEM = 6.6%, p = 0.048]), testosterone (13.8% [SEM = 4.7%, p = 0.048]), and SHBG (11.8% [SEM = 3.5%, p = 0.02]) increased significantly in the T3 challenge only. Moreover, prolactin significantly decreased in both rhTSH and T3 challenges (-8.8% [SEM = 3.4%, p = 0.048] and -12.0% [3.3%, p = 0.004], respectively) as did cortisol (-14.8% [SEM = 3.6%, p &lt; 0.001] and -15.6% [SEM = 3.5%, p &lt; 0.001]). There was no significant interaction with type of challenge, sex, or familial longevity, except for prolactin in the rhTSH challenge (p = 0.004) which decreased significantly in men only.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Upon modulation of thyroid status, changes were observed in IGF-1, prolactin, and cortisol. In the T3 challenge, LH, testosterone, and SHBG increased in men. Observed changes are hypothesized to be driven by (f)T3.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Depending on age, sex, and familial longevity, alterations in thyroid status occur frequently and often co-occur with differences in other hormonal axes. However, studies that explore the effects of thyroid status modulation on other hormonal axes remain scarce. We aimed to determine the effects of thyroid status modulation on prolactin, IGF-1, cortisol, LH, testosterone, and SHBG levels. We also explored whether effects differed depending on type of challenge, sex, and familial longevity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data were gathered from two single-arm challenge studies comprising an intramuscular injection of 0.1 mg recombinant human TSH (rhTSH, N = 29) or 100 µg T3 orally (N = 27) in healthy older individuals. Changes in hormone concentration profiles relative to baseline were determined for 4 and 5 days, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;IGF-1 increased with a maximum of 6.3% (SEM = 1.6%, p = 0.002) in the rhTSH challenge and 8.8% (SEM = 1.6%, p &lt; 0.001) in the T3 challenge, while LH (19.3% [SEM = 6.6%, p = 0.048]), testostero","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-12"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770694","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":"Clinical and Genetic Factors Associated with Neuroendocrine Neoplasms: A UK Biobank Study.","authors":"Harry David Green, Marie Line El-Asmar, Brian Rous, Gareth Hawkes, Maria Trinidad Moreno-Montilla, Christina Thirlwell, John Ramage","doi":"10.1159/000545114","DOIUrl":"10.1159/000545114","url":null,"abstract":"<p><strong>Introduction: </strong>Incidence of neuroendocrine neoplasms (NENs) is rising globally, yet clinical and genetic factors remain poorly understood. Evidence for the role of obesity is conflicted, and studies on prospectively collected data are sparse. We aimed to identify clinical and germline genetic risk factors associated with NEN in the UK Biobank.</p><p><strong>Methods: </strong>Cases of NEN were identified in the UK Biobank's cancer registry data (N∼500,000). Using a combination of ICD-O3 codes for cancer site and histology, NEN cases were stratified into neuroendocrine tumour (NET), neuroendocrine carcinoma (NEC), and small/large cell lung cancer (SLCLC). A Cox proportional hazards model was used to test for an association between clinical phenotypes and increased NEN risk, and a gene burden test in Regenie was used to test for causal variants in the exome sequencing data.</p><p><strong>Results: </strong>We identified 704 NET, 340 NEC, and 550 SLCLC cases. Obesity (BMI or waist-hip ratio) and lower cholesterol (LDL, HDL, or total) had a significantly significant association with NEN risk; however, the effect size was marginal. Smoking and HbA1c were associated only with SLCLC. Air pollution was not significantly associated when adjustment was made for socio-economic status. We replicated a known germline association between loss of function variants in MEN-1 and NEC, but did not detect any novel association in exome variants.</p><p><strong>Conclusion: </strong>This is the first large prospective population-based study to identify potential clinical and genetic risk factors for NEN and define a novel phenotype in the UK Biobank. More research is needed to establish whether these relationships are causal. The exome study was underpowered, and future work in this area should focus on meta-analysing multiple large datasets.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"924-928"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625348","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}