Neuroendocrinology最新文献

{"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":"Are There Connections between the Neuroendocrine and Dopamine Systems in Bipolar Disorder?","authors":"Jacqueline Trouillas, Bruno Claustrat, Emmanuel Henry, Jacques Lemius, Irina Alafuzoff, Serge Nataf","doi":"10.1159/000547042","DOIUrl":"10.1159/000547042","url":null,"abstract":"<p><strong>Background: </strong>Bipolar disorder (BPD) represents a frequent and disabling disease, characterized by the occurrence of extreme mood swings leading to episodes of depression or mania. Although dysfunctions in dopamine (DA) neurotransmission are increasingly recognized as key determinants of BPD, little attention has been given to the biological factors which may shape such a cyclicity of mania and depression.</p><p><strong>Summary: </strong>We propose that BPD may result, at least in part, from skewed connections between the neuroendocrine system, the DA system, and the hypothalamic clock center. First, we provide a brief description of the hypothalamic-pituitary complex, i.e., the core anatomical structure of the neuroendocrine system. We then review clinical data demonstrating the frequent onset of BPD at menopause, during postpartum or in peri-pubertal periods, suggesting that hormonal changes, under neuroendocrine regulation, may favor the clinical expression of BPD. Finally, we revisit the DA hypothesis of BPD and propose that both the hypothalamic clock center and the hypothalamic-pituitary axis exert rheostat effects on the regulation of mood by DA. Thus, in individuals with a genetically determined predisposition to BPD, an alteration of such rheostat functions may translate into a hyper- or hypo-activity of the DA system. Potential therapeutic implications and future research directions are discussed.</p><p><strong>Key messages: </strong>BPD may be related to altered connections between the DA system, the neuroendocrine system and the hypothalamic clock center. We hope this article will provide a basis for future interactions between endocrinologists, neurobiologists, and psychiatrists.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"770-785"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775872","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":"The French Neuroendocrinology Is Enriched by Its Diversity.","authors":"David Vaudry","doi":"10.1159/000543954","DOIUrl":"10.1159/000543954","url":null,"abstract":"","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"101-102"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189004","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":"A Comprehensive Target Panel Allows to Extend the Genetic Spectrum of Neuroendocrine Tumors.","authors":"Uliana A Tsoy, Polina S Sokolnikova, Ekaterina N Kravchuk, Pavel A Ryazanov, Alexandra A Kozyreva, Yulia V Fomicheva, Liana S Aramisova, Tatiana L Karonova, Anna A Kostareva, Elena Grineva","doi":"10.1159/000542223","DOIUrl":"10.1159/000542223","url":null,"abstract":"<p><strong>Introduction: </strong>Neuroendocrine tumors (NETs) frequently have a genetic basis, and the range of genes implicated in NET development continues to expand. Application of targeted gene panels (TGPs) in next-generation sequencing is a central strategy for elucidating novel variants associated with NET development.</p><p><strong>Methods: </strong>In this study, we conducted comprehensive molecular genetic analyses using TGP on a cohort of 93 patients diagnosed with various NETs subtypes, mainly accompanied by various endocrine syndromes: insulinoma (n = 26), pheochromocytoma and paraganglioma (PPGL) (n = 38), parathyroid adenoma (n = 18, including three with insulinoma), and NETs of other locations (n = 14). The TGP encompassed genes linked to diverse NETs and other hereditary endocrine disorders, with subsequent variant classification according to the American College of Medical Genetics and Genomics guidelines.</p><p><strong>Results: </strong>Among the identified variants, 20 were found in genes previously linked to specific tumor types, and 10 were found in genes with a limited likelihood and unclear molecular mecanisms of association with observed NETs. Remarkably, 13 variants were discovered in genes not previously associated with the NETs observed in our patients. These genes, such as ABCC8, KCNJ11, KLF11, HABP2, and APC, were implicated in insulinoma; ZNRF3, GNAS, and KCNJ5 were linked with PPGL; parathyroid adenomas were related to variants in SDHB and TP53; while NETs of other locations displayed variants in APC and ABCC8.</p><p><strong>Conclusion: </strong>Our study demonstrates that utilizing broad TGP in examining patients with various functioning NETs facilitates the identification of new germinal variants in genes that may contribute to the diseases. The verification of revealed findings requires research in vaster sample.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"381-401"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624707","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":"Lu-PRRT Used More Intensively on Advanced Gastro-Entero-Pancreatic and Lung Neuroendocrine Neoplasms: Preliminary Results on Toxicity from a Randomized Study.","authors":"Ilaria Grassi, Silvia Nicolini, Irene Marini, Federica Matteucci, Nicoletta Ranallo, Valentina Di Iorio, Anna Sarnelli, Flavia Foca, Manuela Monti, Lucia Fabbri, Lorenzo Fantini, Alice Rossi, Giovanni Paganelli, Stefano Severi, Maddalena Sansovini","doi":"10.1159/000542328","DOIUrl":"10.1159/000542328","url":null,"abstract":"<p><strong>Introduction: </strong>Lu-PRRT in neuroendocrine tumors is usually delivered with a total cumulative activity (TCA) of 29.6 GBq, divided into 4 cycles and with fixed interval between cycles (IBCs) of 8 weeks. Based on previous radiobiological studies, reducing IBC could improve efficacy without increasing toxicity. The purpose of this study was to evaluate safety of Lu-PRRT with two different IBC: intensive (every 5 weeks) or standard (every 8-10 weeks).</p><p><strong>Methods: </strong>From May 2016 to July 2018, patients with advanced and progressive GEP and bronchial NENs were enrolled in a prospective randomized phase II study. Patients with risk factors for toxicity (RF) were planned for a TCA of 18.5 GBq, patients without RF of 27.8 GBq, divided into 5 cycles. Patients were then randomly assigned to be treated according to the intensive or to the standard IBC. Toxicity was monitored according to CTCAE.</p><p><strong>Results: </strong>One hundred and twenty patients (61 in the intensive group and 59 in the standard one) were evaluable for overall toxicity. Five patients (4.1%) had major (G3) hematological toxicity, 2 in the intensive group and 3 in the standard one. Other G3 toxicities related to creatinine, alanine aminotransferase, nausea, and asthenia were observed in the intensive group. 112 patients (54 in the intensive group and 58 in the standard one) performed at least 2 cycles and were also evaluable for cycle-by-cycle toxicity, resulting similar between the two groups.</p><p><strong>Conclusion: </strong>According to our preliminary results, Lu-PRRT administered intensively could be considered as safe as the standard schedule, when TCA is chosen according to the RF. Further data are needed to confirm these results.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"434-445"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687716","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":"The Novel SSTR3 Full Agonist ITF2984 Shows Antitumor Properties against Pancreatic Neuroendocrine Tumors.","authors":"Margarita Bistika, Alessandro Marangelo, Francesco Ascione, Nicole Valentini, Francesco Fedeli, Jörg Schrader, Daniela Modena, Christian Steinkühler, Natalia S Pellegata","doi":"10.1159/000543136","DOIUrl":"10.1159/000543136","url":null,"abstract":"<p><strong>Background: </strong>Somatostatin analogs (SSAs) binding to and activating somatostatin receptors (SSTRs) have been extensively used for the treatment of neuroendocrine tumors (NETs). The currently approved synthetic SSAs have high affinity for SSTR2 (octreotide/lanreotide) or for SSTR2 and SSTR5 (pasireotide). These agents have shown symptom control and antiproliferative effects in subsets of NET patients and this was associated with the expression of the targeted SSTRs. Pancreatic NETs (Pan-NETs) are uncommon tumors with a propensity to metastasize. For unresectable advanced Pan-NETs expressing SSTRs, SSAs are the first-line medical therapy. Pan-NETs express mainly SSTR1, SSTR2, and SSTR3 and thus should respond to agonists targeting SSTR3.</p><p><strong>Summary: </strong>We evaluated the efficacy of ITF2984, a novel multireceptor agonist with specificity for SSTR3, against Pan-NET cells representative of well-differentiated, functioning tumors, and expressing high levels of SSTR3. The effect of ITF2984 on cell proliferation/viability and on its ability to promote apoptosis and suppress hormone secretion was evaluated in 2D and 3D organotypic culture systems. Pasireotide was tested in parallel for comparative purposes.</p><p><strong>Key message: </strong>We found that ITF2984 is as effective as pasireotide at inhibiting both proliferation/viability and hormone secretion, as well as at inducing apoptosis of Pan-NET cells grown as both 2D monolayers and 3D spheroids. High-dose ITF2984 elicits structural alterations in Pan-NET 3D spheroids compatible with cell death more effectively than pasireotide. Altogether, ITF2984 may represent a useful alternative to pasireotide for the medical treatment of Pan-NETs and other tumors with elevated SSTR3 expression.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"446-459"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903507","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}