Journal of Neuroendocrinology最新文献

{"title":"Ovarian hormones and high-fat diet duration distinctively modulate hypothalamic chemokine profile","authors":"Alexia Guimaraes Batista Augusto,&nbsp;Giovanna Ariozi dos Santos,&nbsp;Igor Vinicius Sousa Cavalheiro,&nbsp;Vinicius Stefanini Mantovan,&nbsp;Larissa Silva Bergantini,&nbsp;Nicolly Porto Marin,&nbsp;Ester dos Santos Alves,&nbsp;Licio Augusto Velloso,&nbsp;Natalia Ferreira Mendes","doi":"10.1111/jne.70215","DOIUrl":"10.1111/jne.70215","url":null,"abstract":"<p>Excessive intake of saturated fats triggers inflammation in the hypothalamus, a key regulator of energy balance. In the chronic phase of this inflammatory response, bone marrow-derived and lymphoid cells are chemoattracted to this region, partially mitigating high-fat diet (HFD)-induced metabolic impairments. In rodents, the onset and magnitude of this inflammation differ between males and females, reflecting sex-specific patterns of metabolic regulation. However, how the hypothalamic chemokine profile evolves during HFD-induced inflammation, and whether it is influenced by biological sex, remains unclear. Here, male and female C57BL/6J mice were fed a HFD for 1, 3, 14, or 28 days. To isolate the role of ovarian hormones in modulating hypothalamic chemokine profile, we also analyzed ovariectomized (OVX) females with or without estrogen replacement. Quantitative polymerase chain reaction-based expression analysis revealed that most chemokines and their receptors were transiently modulated in the hypothalamus during the course of the HFD exposure, showing reduced levels in the acute phase and normalization during the chronic phase. Despite the modest sex-dependent effects observed, messenger RNA expression of the chemokine receptor C–X–C motif chemokine receptor 3 (CXCR3) was significantly higher in females than in males after 14 and 28 days of HFD, suggesting faster recruitment of CXCR3⁺ immune cells that may contribute to female protection against metabolic dysfunction. Females lacking ovarian hormone production displayed increased hypothalamic expression of <i>Cxcr3</i> and <i>Ccl2</i>. Only <i>Cxcr3</i> expression was partially normalized by estradiol treatment, suggesting that non-estrogenic ovarian factors may play a role in modulating specific chemokine signaling pathways. Together, our findings show that hypothalamic chemokine signaling is dynamically and transiently regulated throughout the phases of HFD-induced inflammation, with <i>Cxcr3</i> modulation by HFD and ovarian hormones contributing to sex-specific resilience against metabolic inflammation.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 7","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317668","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":"Methodological and inferential limits before abandoning follow-up in node-negative typical lung carcinoids","authors":"Luca Bertolaccini,&nbsp;Francesca Spada,&nbsp;Lorenzo Spaggiari,&nbsp;Nicola Fazio","doi":"10.1111/jne.70222","DOIUrl":"https://doi.org/10.1111/jne.70222","url":null,"abstract":"","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 7","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306019","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":"Characteristics, management, and outcomes of patients with VIPoma–A retrospective analysis of the ENETS database","authors":"Detlef K. Bartsch,&nbsp;L. Mais,&nbsp;L. de Mestier,&nbsp;E. Baudin,&nbsp;G. Kaltsas,&nbsp;J. Hofland,&nbsp;R. Garcia-Carbonero,&nbsp;E. Tiensuu Janson,&nbsp;M. G. McNamara,&nbsp;M. Andreassen,&nbsp;S. Grozinsky-Glasberg,&nbsp;F. Spada,&nbsp;H. Leupe,&nbsp;F. Panzuto,&nbsp;M. Fleschen,&nbsp;H. Klinkhammer","doi":"10.1111/jne.70219","DOIUrl":"https://doi.org/10.1111/jne.70219","url":null,"abstract":"<p>Introduction: VIPoma is an extremely rare functioning pancreatic neuroendocrine tumor. Therefore, data regarding treatment and outcome are very limited. Aim (s): This multicenter study aimed to analyze clinical characteristics, real-world management, and outcomes of patients with VIPoma. Methods: Patients with VIPoma treated in a 20-year period at 14 referral centers for neuroendocrine tumors (NET) were collected in the ENETS Database. Clinical characteristics, therapeutic interventions, and outcomes were analyzed retrospectively. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results: Of 70 patients, 59 (54% male) with a median age of 55 years were included. Forty-six (78%) patients were diagnosed due to the classical watery diarrhea–hypokalemia–achlorhydria (WDHA) syndrome, and 40 (68%) presented with distant metastases at diagnosis. Fifty-two (88%) had serum VIP levels &gt;2 times the upper normal limit and the median Ki-67 index was 5% (range 1%–40%). Surgery of the primary VIPoma was performed in 32 (54%), with curative intent in 22 (37%). In patients with stage I–III disease (<i>n</i> = 19), long-term cure was achieved in only 26% (5/19), with a median DFS of 81 (95%-CI: 1–215) months and 10-year OS of 78% (95%-CI: 61%–100%). In stage IV patients (<i>n</i> = 53, 40 at diagnosis, 13 disease progression), the sequence and type of 354 treatment lines varied, while SSA (<i>n</i> = 77, 22%), loco-regional liver-directed therapy (<i>n</i> = 72, 20%), and chemotherapy (<i>n</i> = 69, 19%) were most often applied. Median OS for patients with stage IV at diagnosis was 142 (95%-CI: 87–not available (NA)) months with 10-year survival of 50% (95%-CI: 35%–73%). Conclusion: Patients with VIPoma treated at NET centers have relatively favorable survival, even with distant metastases at diagnosis, although long-term cure rates remain low.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 7","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306018","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":"Author reply on: Prolactin-adjusted inferior petrosal sinus sampling: Pituitary and ectopic adrenocorticotropic hormone-dependent Cushing syndrome","authors":"Vera E. Sprenkeler,&nbsp;Antonius E. van Herwaarden,&nbsp;Annenienke C. van de Ven,&nbsp;Benno Kusters,&nbsp;Sjoerd F. M. Jenniskens,&nbsp;Romana T. Netea-Maier,&nbsp;Joanne M. de Laat","doi":"10.1111/jne.70218","DOIUrl":"10.1111/jne.70218","url":null,"abstract":"","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258497","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":"Sex-differential associations of MC3R p.F45S with human metabolic profile","authors":"Tanya C. Kaur,&nbsp;Andrew R. Wood,&nbsp;Gareth Hawkes,&nbsp;Robin N. Beaumont,&nbsp;Kartik Chundru,&nbsp;Michael N. Weedon,&nbsp;Hugh D. Piggins,&nbsp;Kate L. J. Ellacott","doi":"10.1111/jne.70214","DOIUrl":"10.1111/jne.70214","url":null,"abstract":"<p>Obesity and related metabolic disorders represent major global health challenges, highlighting the importance of understanding the central regulation of energy homeostasis. The melanocortin system is a conserved circuitry governing food intake and other neuroendocrine processes. Within this system, the melanocortin-3 receptor (MC3R) regulates energy and glucose balance, body composition, and linear growth in rodent models, with evidence of sexually dimorphic expression and function. Whether MC3R exerts similar sex-specific effects in humans remains unclear, largely due to the rarity of loss-of-function (LoF) variants. We analysed data from the UK Biobank (UKB), a population-based study comprising 500,000 individuals, to investigate the phenotypic consequences of the rare MC3R LoF variant rs143321797 (p.F45S). Using the largest UKB whole-genome sequencing dataset to date, we performed comprehensive phenotypic analyses, including the first sex-stratified assessment of this variant. Carriage of the MC3R p.F45S variant was associated with differences in adult stature and the timing of sexual maturation. Though the variant was not associated with increased risk of obesity or metabolic disease, carriers exhibited an altered adipose tissue distribution profile characterised by relatively greater subcutaneous fat deposition. Our findings independently validate the role of MC3R in human stature and sexual maturation and identify a previously unreported association with adipose tissue distribution. The absence of increased obesity or metabolic disease risk in MC3R p.F45S carriers of this study, together with a subcutaneous-biased adipose distribution, suggests that MC3R may influence metabolic health through regulation of adipose tissue distribution rather than overall adiposity.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264798","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":"Promising but not yet definitive: Interpreting prolactin-adjusted inferior petrosal sinus sampling in adrenocorticotropic hormone-dependent Cushing syndrome","authors":"Omer Denizhan Tatar","doi":"10.1111/jne.70217","DOIUrl":"10.1111/jne.70217","url":null,"abstract":"","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258529","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":"The aging paradox of Cushing's syndrome: Stress without clear senescence?","authors":"Israel Nunes Silveira,&nbsp;Alexandro Guterres","doi":"10.1111/jne.70213","DOIUrl":"10.1111/jne.70213","url":null,"abstract":"<p>Cushing's syndrome (CS), characterized by chronic endogenous hypercortisolism and disruption of the normal circadian cortisol rhythm, represents a unique human model for investigating the interplay between stress endocrinology and biological aging. Glucocorticoid excess drives multiple convergent aging pathways: it suppresses telomerase activity and may accelerate telomere attrition, induces durable epigenetic remodeling, including hypomethylation of stress-responsive genes such as <i>FKBP5</i>, TET-mediated DNA hydroxymethylation changes, and broad dysregulation of circadian clock <i>loci</i>, and promotes telomere-independent senescence through mitochondrial dysfunction, oxidative stress, and cytokine-driven inflammation. These observations underpin a proposed dual-pathway model of glucocorticoid-accelerated aging, in which direct telomerase suppression and indirect epigenomic remodeling converge on common hallmarks of cellular senescence. However, clinical evidence remains heterogeneous and inconclusive: studies of leukocyte telomere length in CS report discrepant results attributable to assay platform differences, failure to correct for glucocorticoid-induced lymphopenia, small sample sizes, and predominant reliance on cross-sectional designs. Epigenetic clocks capable of quantifying biological age acceleration, particularly second-generation tools such as GrimAge and DunedinPACE, have not yet been applied to CS cohorts, representing a critical evidence gap. Furthermore, virtually all molecular aging measurements in CS have been performed in peripheral blood, leaving the causal chain from glucocorticoid excess to organ-level aging and excess mortality empirically unproven. Rather than a definitive null result, this paradox reveals that CS is an underexplored natural experiment: the syndrome's defined onset, quantifiable cortisol exposure, and surgically curable course offer a unique before-after design for testing whether stress-induced endocrine disruption genuinely accelerates biological aging through telomere and epigenetic mechanisms.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 6","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218169","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":"Limited nesting stress in mice as a model to study neuroimmune relationships in postpartum depression","authors":"Marie Armbruster,&nbsp;Ritu Mann-Nüttel,&nbsp;Shivani Mandal,&nbsp;Karen-Anne McVey Neufeld,&nbsp;Paul Forsythe","doi":"10.1111/jne.70216","DOIUrl":"10.1111/jne.70216","url":null,"abstract":"<p>Postpartum depression (PPD) is a mood disorder that affects the ability of mothers to engage with and care for their infants. Stress exposure is known to be a major predisposing factor for PPD, while immune factors such as T regulatory cells (Tregs) are also hypothesized to influence the development of the disorder. Here we assessed limited nesting (LN) in mice, with or without depletion of Tregs through anti-CD25 antibody treatment, as a potential model to investigate the relationship between stress and the immune system in PPD. Dams and their pups were exposed to LN from post-natal day 3–10 and maternal behaviour was evaluated over this period followed by assessment of maternal self-care using the splash test. Gene expression in selected brain regions and the peripheral lymphocyte profile were also assessed. LN exposure led to a significant increase in aggressive behaviour towards the pups and altered grooming in the splash test. These effects on behaviour were associated with brain region specific changes in expression of several genes related to depression and maternal behaviour and with increased levels of Tregs in the periphery. When LN was combined with anti-CD25 antibody treatment, there were further deficits in nursing behaviour and changes in the brain circuitry related to lactation and stress. Our study indicates that LN in mice may be a useful model for studying neuroimmune relationships in certain aspects of PPD. Our data also suggest that post-partum regulatory immune changes may mitigate effects of stress on brain circuitry associated with maternal behaviour, lactation and stress.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 6","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70216","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148226038","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":"Altered responses to ghrelin and food cues in AgRP neurons during pregnancy and lactation","authors":"C. L. Murrell,&nbsp;M. R. Perkinson,&nbsp;Z. B. Andrews,&nbsp;D. R. Grattan,&nbsp;S. R. Ladyman","doi":"10.1111/jne.70202","DOIUrl":"10.1111/jne.70202","url":null,"abstract":"<p>Pregnancy and lactation trigger many metabolic adaptations, including increased food intake to support the energy demands of the growing foetus and then to provide nutrition through milk production after birth. Ghrelin, an orexigenic hormone, activates agouti related peptide (AgRP) neurons in the arcuate nucleus to promote food intake. Here, we investigated the hypothesis that increased sensitivity to ghrelin during pregnancy and lactation may contribute to elevated maternal food intake. Acute food intake was measured after a single dose of ghrelin or vehicle across reproductive states including virgin, pregnant (Day 8 and Day 15), lactating (Day 10) mice and dams 2 weeks after weaning. In vivo GCaMP fibre photometry of the AgRP neuron population was used to measure AgRP neuronal response to ghrelin. Unlike virgin mice, pregnant mice did not show an acute increase in food intake after ghrelin injection, while ghrelin-treated lactating mice showed a greater feeding response than virgin mice. After weaning, dams showed a similar increase in food intake to that seen in virgin mice. In contrast to the loss of feeding response to ghrelin, the expected increase in growth hormone (GH) in response to ghrelin was observed in both pregnancy and lactation. Across all of the reproductive states, a significant increase in AgRP neuron activity was observed in response to exogenous ghrelin administration, although the magnitude was slightly reduced in late pregnancy. Furthermore, the ghrelin-induced increase in c-Fos expression in AgRP neurons was similar in all reproductive states, indicating that AgRP neurons remained responsive to ghrelin despite the absence of a food-intake response to ghrelin during pregnancy. Interestingly, the expected drop in AgRP neuron activity in response to the presentation of food was absent during late pregnancy and lactation. The absence of a food consumption-mediated inhibition of AgRP neuron activity suggests that an attenuated response of the AgRP neurons to feedback signals associated with eating may contribute to increases in meal duration during pregnancy and lactation. Overall, these results indicate that ghrelin resistance develops during pregnancy, suggesting that ghrelin does not contribute to elevated food intake during pregnancy. In lactation, however, enhanced ghrelin sensitivity may contribute to elevated maternal food intake. These results also indicate that adaptations to ghrelin sensitivity in pregnancy and lactation are transient as 2 weeks after weaning our results are similar to the virgin state.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 6","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210699","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":"Nonapeptide molecular evolution during the adaptive radiation of Tanganyika cichlids","authors":"Pol Sorigue,&nbsp;Walter Salzburger,&nbsp;Rui F. Oliveira","doi":"10.1111/jne.70203","DOIUrl":"10.1111/jne.70203","url":null,"abstract":"<p>Oxytocin (OT) and vasotocin (VT) are evolutionarily conserved nonapeptides that regulate a wide range of physiological and behavioral processes in vertebrates. Their receptor families have undergone gene duplications that facilitated functional diversification throughout vertebrate evolution. Using the diverse cichlid species in Lake Tanganyika, which have undergone repeated evolutionary transitions between social phenotypes, we investigated the molecular evolution of the nonapeptide system and its potential involvement in social behavior. We performed a positive selection analysis based on the <i>dN/dS</i> ratio and examined the correlation between amino acid variants and two social phenotypes. We also analysed gene expression data to explore associations between brain receptor expression and social phenotype variation. Our findings reveal that, while most sites in nonapeptide receptors are under strong purifying selection, a few sites– primarily in the extended intracellular loop 3 (IL3) of VTR2A receptors– show signatures of positive selection. Additionally, a specific amino acid in VTR2Aa correlates with pair-bonding, suggesting its potential role in social attachment. Gene expression analyses further revealed that components of the nonapeptide system, including VTR2Bb and OT, are differentially expressed across social phenotypes, supporting a role for regulatory variation alongside coding changes. Together, these findings provide new insights into how conserved neuroendocrine systems contribute to social diversity in cichlids.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 6","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205078","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}