Journal Of Neuroendocrinology[JOURNAL]
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200 papers
Oxytocin supports the barrier integrity of brain endothelial cells via oxytocin receptors.
Paolini C, Piacentini F, Amato S … +2 more , Busnelli M, Chini B
J Neuroendocrinol · 2026 Mar · PMID 41806820 · Full text
Oxytocin plays an emerging role in vascular regulation and neuroprotection, but its effect on brain endothelial cells and blood-brain barrier functionality is not fully defined. To assess oxytocin and vasopressin recepto...
Oxytocin plays an emerging role in vascular regulation and neuroprotection, but its effect on brain endothelial cells and blood-brain barrier functionality is not fully defined. To assess oxytocin and vasopressin receptor expression in brain endothelial cells and to evaluate the impact of oxytocin on endothelial barrier integrity under physiological (normoxic) and low-oxygen (hypoxic) conditions we used bEnd.3 brain endothelial cells. Receptor expression was evaluated by real-time PCR and RNAscope. Oxytocin treatment was applied under normoxic and hypoxic conditions and Transendothelial Electrical Resistance and tight junction proteins expression (claudin-5, zonula occludens-1) were analyzed. Our results indicate that 1) bEnd.3 cells express oxytocin and V1a receptors. 2) Activation of the oxytocin receptor enhanced brain endothelial barrier integrity by increasing claudin-5 expression and its localization at the cell surface, without affecting zonula occludens-1.3) Under hypoxic conditions, oxytocin preserved Transendothelial Electrical Resistance and claudin-5 expression at the cell membrane, thereby preventing endothelial barrier impairment. Our findings demonstrate that oxytocin receptor signaling enhances and preserves brain endothelial barrier function, underscoring the relevance of oxytocin in neurovascular regulation and its therapeutic potential in blood-brain barrier dysfunction.
Proteomic insights into the invasiveness and tumor progression of non-functioning pituitary adenomas: A scoping review.
Skoglund T, Köster L, Thorsell A … +3 more , Ragnarsson O, Johannsson G, Hallén T
J Neuroendocrinol · 2026 Mar · PMID 41795170 · Full text
Nonfunctioning pituitary adenomas (NFPAs) are common intracranial tumors that, despite being histologically benign, can exhibit invasive growth, as well as postoperative tumor progression. Surgical resection is the prima...
Nonfunctioning pituitary adenomas (NFPAs) are common intracranial tumors that, despite being histologically benign, can exhibit invasive growth, as well as postoperative tumor progression. Surgical resection is the primary treatment of choice; however, residual tumor tissue is frequently observed, with between 30% and 50% of these cases subsequently experiencing regrowth. The molecular mechanisms governing NFPA behavior remain poorly understood, and robust prognostic biomarkers are still lacking despite genomic and transcriptomic studies. Mass spectrometry (MS)-based proteomics enables large-scale, global protein quantification and monitoring of changes in protein expression, which could identify markers of tumor behavior as well as potential new therapeutic targets. This review synthesizes existing proteomic research on NFPAs and identifies candidate biomarkers and dysregulated pathways associated with invasiveness and tumor progression. We used PubMed, the Cochrane Library, and Scopus to perform a structured and comprehensive literature search of studies published since the year 2000 that applied MS-based proteomics to evaluate NFPAs. The identified studies were grouped into three main categories: (1) proteomic differences between NFPAs and normal pituitary glands, (2) biomarkers linked with tumor progression, and (3) molecular signatures distinguishing invasive from noninvasive NFPAs. Among the 30 included studies, 15 compared NFPAs with normal pituitary tissue and reported altered protein expression, metabolic reprogramming, and spliceosome dysregulation. Only two studies addressed tumor progression, showing associations with RNA processing, energy metabolism, and β-catenin phosphorylation. Studies evaluating NFPA invasiveness (n = 16) highlighted altered extracellular matrix remodeling and dysregulated PI3K-Akt and MAPK/ERK signaling along with specific proteins, including Ezrin and β-catenin. Across themes, recurrent alterations in MAPK/ERK, PI3K-Akt-mTOR, Wnt/β-catenin, and IL6/JAK/STAT3 signaling suggest that NFPA biology is driven by interconnected pathways rather than isolated molecular events. Sample sizes were generally small, with more than 50% of studies analyzing less than 10 NFPAs, and only one study including up to 100 NFPAs. Methodological heterogeneity and lack of validation remain major limitations. Although modern proteomic studies provide valuable insights into NFPA biology and particularly invasiveness, investigations on mechanisms of progression are limited. Moreover, robust biomarkers have not yet been established, and most findings remain exploratory due to small sample sizes and methodological heterogeneity. Future research should focus on larger, prospective cohorts, integration of clinical and imaging data with multi-omics approaches, and standardized protocols for sample handling and preparation to enhance reproducibility. Such efforts are needed to translate proteomic discoveries into clinically useful biomarkers and novel therapeutic strategies.
Biomarkers of hypothalamic melanocortin activity in human energy balance.
Wardlaw SL, Smiley RM
J Neuroendocrinol · 2026 Mar · PMID 41791764 · Publisher ↗
The hypothalamic melanocortin system, comprised of proopiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, regulates energy balance but studies in humans are limited by lack of biomarkers to assess brain me...
The hypothalamic melanocortin system, comprised of proopiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, regulates energy balance but studies in humans are limited by lack of biomarkers to assess brain melanocortin activity. Previous studies evaluated POMC concentrations in human CSF in relation to BMI and leptin and to weight loss, including pharmacotherapy with lorcaserin which targets POMC neurons, showing that lower baseline POMC predicted a better weight loss response to lorcaserin. We performed a retrospective analysis of baseline CSF POMC levels in 139 healthy weight-stable individuals without diabetes or neurologic disease who participated in previous studies, including a subgroup analysis of 70 subjects spread equally across the BMI spectrum (19.2-57.3) and in 97 subjects with obesity. POMC was measured in CSF and AgRP was measured in CSF and plasma by sensitive 2-site ELISAs. Mean CSF POMC was lower in individuals with elevated versus normal BMI (200 vs. 269 fmol/mL; p = .0003) and strong negative correlations between CSF POMC and both BMI and leptin were found in 70 subjects across the BMI spectrum (p < .0001); this remained significant in all 139 subjects but not in 97 with obesity. The cohort with obesity included some very low CSF POMC levels (bottom 10%) that do not overlap with non-obese subjects. Strong positive correlations were noted between CSF POMC and AgRP in both CSF and plasma in all groups, including the subgroup with obesity, providing evidence that activities of both sets of neurons may be linked independently of leptin and BMI. Importantly CSF POMC levels remained remarkably constant when nine weight-stable subjects were studied twice over several years. In summary, CSF POMC was lower in individuals with elevated BMI and correlated negatively with BMI and leptin across the BMI spectrum but not within a cohort with obesity. However, the cohort with obesity contained subjects with very low CSF POMC levels that may indicate POMC deficiency and predict treatment response to melanocortin agonists. It remains to be determined if alternative biomarkers associated with low CSF POMC can be identified for use in the clinical setting.
Effects of combined prenatal exposure to air pollution and maternal stress on social behavior and oxytocin and vasopressin systems in male and female mice.
Stoehr MC, Martin EM, Babalola JT … +6 more , Xue J, Kern MJ, Li NY, Winters MF, Bhagwagar S, Smith CJ
J Neuroendocrinol · 2026 Mar · PMID 41787616 · Full text
Prenatal exposures to air pollution and maternal psychosocial stress are each associated with increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), and epidemiological work suggests th...
Prenatal exposures to air pollution and maternal psychosocial stress are each associated with increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), and epidemiological work suggests that concurrent exposure to these risk factors may be particularly harmful. This is important given that the same populations often bear the brunt of both toxicant and psychosocial stress burdens. Social impairments are a defining symptom in ASD. Previous work modeling combined prenatal exposure to diesel exhaust particles (DEPs) and maternal stress (MS) in rodents has found male-biased social deficits in offspring, as well as changes to neuroimmune processes and the gut microbiome. However, the precise neural circuits on which these exposures converge to impact social behavior are unclear. Oxytocin (OXT) and vasopressin (AVP) are neuropeptides critical to the regulation of social behavior across species, signaling primarily at the oxytocin receptor (Oxtr) and vasopressin V1a receptor (V1aR) in the brain. Here, we hypothesized that OXT and/or AVP expression would be reduced in the brain following DEP/MS exposure. Following prenatal exposure to DEP/MS or the vehicle/control condition (VEH/CON), we measured maternal and offspring outcomes during the perinatal period, social and anxiety-like behavior during adolescence, OXT and AVP cell/fiber density, and Oxtr and Avpr1a mRNA expression in early adulthood in several brain regions in both males and females. We observed a decrease in interaction time in DEP/MS males as compared to VEH/CON in the sociability assay and a decrease in social novelty preference in DEP/MS females as compared to VEH/CON. No effects of sex or treatment were observed on OXT or AVP cell number or fiber density in the hypothalamic regions assessed. However, numerous sex differences were observed in Oxtr and Avpr1a mRNA. Moreover, Avpr1a mRNA was significantly increased following DEP/MS exposure in the nucleus accumbens in both sexes and trended towards increasing in the dorsal hippocampus. Together, these findings suggest that DEP/MS exposure has a stronger impact on female social behavior than previously observed. Moreover, while DEP/MS exposure does not appear to impact OXT or AVP expression in the brain, V1aR expression is modulated by DEP/MS exposure in the nucleus accumbens.
23rd Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, 4 - 6 March 2026.
J Neuroendocrinol · 2026 Mar · PMID 41776950 · Publisher ↗
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Remembering Leo P. Renaud: Mentor, physiologist, friend.
Bourque CW, Ferguson AV, Jhamandas JH … +1 more , Pittman QJ
J Neuroendocrinol · 2026 Mar · PMID 41771262 · Publisher ↗
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Low-dose testosterone administration and oestrogen synthase availability in the female brain: A pilot study.
Dubol M, Jonasson M, Takahashi K … +7 more , Wikström J, Watanabe Y, Antoni G, Lubberink M, Biegon A, Sundström-Poromaa I, Comasco E
J Neuroendocrinol · 2026 Mar · PMID 41771256 · Full text
Testosterone and oestrogens play significant roles in female physiology, extending beyond reproductive functions to influence brain health, mood regulation, and behaviour. Testosterone low-dose therapy is increasingly co...
Testosterone and oestrogens play significant roles in female physiology, extending beyond reproductive functions to influence brain health, mood regulation, and behaviour. Testosterone low-dose therapy is increasingly considered for alleviating sexual dysfunction symptoms in postmenopausal women, and has been recently investigated as therapy for depressive symptoms, though the mechanisms and safety of this approach are not entirely clear. Specifically, the effects of testosterone use on brain oestrogen synthase (aromatase), which maintains the balance between androgens and oestrogens, remain unexplored. This study investigated the effects of short-term, low-dose testosterone administration on brain oestrogen synthase availability and associated mood and behavioural changes in healthy women. Healthy women were exposed to 1 week of low-dose testosterone (10 mg/day). Binding of oestrogen synthase was examined by [C]cetrozole positron emission tomography before and during testosterone exposure. Psychometric assessment of depression, anxiety, and aggression was performed at the same time. Peripheral testosterone levels were significantly increased (up to 33-fold) upon treatment, which had no significant effect on brain oestrogen synthase binding in the thalamus, as supported by Bayesian analyses, nor in the hypothalamus and amygdala. Psychometric measures of depression, anxiety, and aggression also remained unchanged by testosterone treatment. These findings suggest that short-term, clinically relevant testosterone administration has no major effects on the brain oestrogen synthase availability in healthy women, which may reassure patients with hypoactive sexual desire disorder considering this treatment. Larger, long-term studies are needed to confirm these results and explore effects in patients with clinical need for testosterone treatment.
Finasteride withdrawal induces anxiety-like behavior and novelty avoidance in adult male rats.
Cioffi L, Diviccaro S, Chrostek G … +4 more , Severino FPU, Giatti S, Scheggia D, Melcangi RC
J Neuroendocrinol · 2026 Mar · PMID 41761643 · Full text
Finasteride, an inhibitor of the enzyme 5alpha-reductase, prescribed for benign prostatic hyperplasia and androgenetic alopecia, induces a wide variety of side effects during treatment and upon withdrawal, like sexual dy...
Finasteride, an inhibitor of the enzyme 5alpha-reductase, prescribed for benign prostatic hyperplasia and androgenetic alopecia, induces a wide variety of side effects during treatment and upon withdrawal, like sexual dysfunction and cognitive and psychological disorders, inducing the so-called post-finasteride syndrome (PFS). Here, we explored the behavioral effects of this drug in adult male rats after subchronic finasteride treatment (20 days) and at drug discontinuation (1 month). We employed multiple behavioral paradigms, including the open field test and elevated plus maze to assess locomotor activity and anxiety, and a novelty-seeking test to evaluate exploratory behavior and approach-avoidance tendencies. Our results revealed a dichotomy between immediate and delayed finasteride effects. While effects after subchronic treatment were mild, significant behavioral alterations emerged at the withdrawal. In particular, pronounced hyperactivity, decreased center exploration in the open field, and marked avoidance of novel stimuli, collectively indicating an anxiety-like behavioral phenotype, were revealed. These results, showing a picture of increased vulnerability, are in agreement with clinical reports in PFS, highlighting the relevance of our model for this condition. Moreover, the data here described strengthen the importance of monitoring patients not only during treatment but also following discontinuation of finasteride therapy.
Biomarker-directed aptamer panels for diagnosis and differentiation of neuroendocrine tumors.
Kjær MB, Jørgensen AG, Fjelstrup S … +6 more , Dupont DM, Bus C, Oversoe SK, Kelsen J, Kjems J, Grønbæk H
J Neuroendocrinol · 2026 Mar · PMID 41761637 · Full text
Neuroendocrine tumors (NETs) are rare tumors that may arise in the small intestine (siNET) or pancreas (pNET). The tumors have heterogeneous clinical characteristics, and diagnosis may be challenging. Current non-invasiv...
Neuroendocrine tumors (NETs) are rare tumors that may arise in the small intestine (siNET) or pancreas (pNET). The tumors have heterogeneous clinical characteristics, and diagnosis may be challenging. Current non-invasive biomarkers perform suboptimally, and novel biomarkers are highly needed. We aimed to investigate the use of RNA aptamer panels, selected by the APTASHAPE technology, in distinguishing healthy individuals from individuals with NET as well as discriminating siNET from pNET. Plasma samples from 68 individuals with NET and 24 healthy individuals were collected and randomly divided into a development set and a test set. A panel of aptamers recognizing disease-specific plasma proteins was selected in the development set, and the accuracy for disease prediction was evaluated in the test set. The aptamer panels demonstrated high discriminative power, accurately distinguishing between healthy individuals and NET patients with AUCs of 0.74 and 0.87 in the development set and test set, respectively. Furthermore, the aptamer panels were able to differentiate between siNET and pNET patients with AUCs of 0.72 in both the development set and the test set. In addition, mass spectrometry analysis identified ITIH2 and IGHG3 as potential novel biomarkers for the diagnosis of NET. The APTASHAPE platform is a capable tool for selecting protein biomarker-directed aptamer panels for the diagnosis of NET and discrimination between siNET and pNET. Furthermore, the identification of ITIH2 and IGHG3 highlights the potential of APTASHAPE to identify novel protein biomarkers in NET.
Adrenarche as a regulator of sensitivity to early adversity.
Herbert J
J Neuroendocrinol · 2026 Mar · PMID 41736470 · Full text
The human brain is highly sensitive to early adversity, which can have long-term consequences for later mental health. It is also a time of rapid learning of social, motor and other skills, including language. It is prop...
The human brain is highly sensitive to early adversity, which can have long-term consequences for later mental health. It is also a time of rapid learning of social, motor and other skills, including language. It is proposed that pre-adrenarche, the only epoch in human development in which cortisol is not accompanied by dehydroepiandrosterone (DHEA) and its sulphated derivative (DHEAS), represents the sensitive period but this is subsequently moderated by the advent of adrenarche and the surge of DHEA(S) at 6-8 years. Cortisol enhances plasticity and the formation of new memories as well as personality traits such as emotionality. DHEA(S) is well known to oppose many of the actions of cortisol on the brain, including those on learning, memory and synaptic function, all reflecting altered plasticity; adrenarche is therefore a time of moderated cortisol activity. Several endocrine-dependent neural mechanisms respond to the neuroendocrine transition at adrenarche, including alterations in perineuronal nets, gene expression of growth factors, serotonin activity, cytokine release and synaptic adaptability. Adrenarche will reduce the detrimental impact of adverse events but stabilise memories and psychological traits acquired during the cortisol-dominated pre-adrenarche epoch. The transition from pre- to post-adrenarche is therefore a highly significant neuroendocrine event in early life, with both potentially beneficial and disadvantageous consequences. This suggests a primary role for adrenarche, for which no function has yet been established.
Neuroendocrine plasticity and crosstalk in pubertal development.
Elias CF, Han X, Garcia-Galiano D … +1 more , Sáenz de Miera C
J Neuroendocrinol · 2026 Feb · PMID 41716006 · Full text
Puberty is a critical developmental stage during which individuals acquire the capacity for sexual reproduction. This transition involves a series of complex biological events primarily orchestrated by the activation of...
Puberty is a critical developmental stage during which individuals acquire the capacity for sexual reproduction. This transition involves a series of complex biological events primarily orchestrated by the activation of the hypothalamo-pituitary-gonadal (HPG) axis. Central to this process are gonadotropin-releasing hormone (GnRH) neurons, which play a key role in regulating reproductive maturation and function throughout life. However, the precise mechanisms that trigger the pubertal increase in GnRH activity remain incompletely understood. Evidence from our laboratory indicates that a profound remodeling of the hypothalamus is crucial for sexual maturation. In this review, we discuss findings from our research utilizing a combination of RNA sequencing, conditional genetic manipulation with mouse models and viral vectors, and systems neuroscience approaches. Our results reveal that the pubertal transition involves changes in the chemical phenotype and site-specific innervation of key hypothalamic neurons. Among these neuronal populations, those expressing growth hormone-releasing hormone (GHRH), kisspeptin, or dopamine transporter (DAT) are the focus of this review. Building upon data from other laboratories, our findings offer new insights into the neural and molecular mechanisms by which the hypothalamus orchestrates sexual maturation.
Responses to medical treatment in patients with metastatic unresectable small intestinal neuroendocrine tumors - A single center study of 378 patients.
Slott C, Langer SW, Oturai P … +8 more , Møller S, Hansen CP, Kjaer A, Holmager P, Klose M, Garbyal RS, Knigge U, Andreassen M
J Neuroendocrinol · 2026 Feb · PMID 41709663 · Full text
Small intestinal neuroendocrine tumors (siNET) are rare malignancies, often diagnosed at advanced stages with metastatic spread. While surgery is the only curative treatment, medical therapies, including somatostatin ana...
Small intestinal neuroendocrine tumors (siNET) are rare malignancies, often diagnosed at advanced stages with metastatic spread. While surgery is the only curative treatment, medical therapies, including somatostatin analogues (SSA), peptide receptor radionuclide therapy (PRRT), and other systemic treatments, are essential for disease stabilization. The aim was to assess median progression free survival (mPFS), and prognostic factors for the most frequently used medical treatment modalities in patients with unresectable disease. It was a retrospective single-center cohort study, including 378 patients diagnosed with siNET between 2000 and 2020. The median overall survival (mOS) for the cohort was 97 (95% CI: 83-111) months. Median PFS for octreotide and lanreotide treatment/treated patients (n = 255) was 30 (95% CI: 24-36) months and 5 years PFS was 32%, with no significant difference between the two agents. Risk factors for disease progression included age, Ki-67 index, and gender (female as a protective factor). Median PFS for PRRT (n = 140) was 31 (95% CI: 25-37) months. Thirty-seven patients who had PFS > 18 months after the first 4 cycles received another 2 cycles of PRRT. Median PFS after the first 4 cycles was 37 (95% CI: 30-44) months versus 10 (95% CI: 6-14) months after the 2 additional PRRT cycles. Patients treated with everolimus had a median PFS of 5 (95% CI: 0.3-10) months, and chemotherapy with streptozocin and 5-fluorouracil resulted in a median PFS of 8 (95% CI: 5-11) months. In conclusion, SSA remains the cornerstone of first-line therapy for unresectable siNET, with PRRT offering a valuable alternative for patients with progression on SSA. Re-introduction of PRRT with 2 additional cycles had reduced efficacy compared with the initial treatment. PFS was short in non-somatostatin receptor-based therapies like everolimus and chemotherapy.
GHSR agonism increases blood glucose but delays food intake in GHSR hyperresponsive rats.
Zizzari P, Ramírez-Penas O, Pons V … +11 more , Oujezdska M, Sammarcelli AL, Saint-Yves T, Chevallier-Chantepie I, Baussart L, Nhan V, Phalip A, Gales C, Cota D, Noble F, Pantel J
J Neuroendocrinol · 2026 Feb · PMID 41689292 · Full text
Severe calorie restriction in mouse models has highlighted the crucial role of the ghrelin system in maintaining glycemia and promoting survival. We hypothesized that if ghrelin acts as a survival signal, enhancing the r...
Severe calorie restriction in mouse models has highlighted the crucial role of the ghrelin system in maintaining glycemia and promoting survival. We hypothesized that if ghrelin acts as a survival signal, enhancing the responsivity of the GH secretagogue receptor (GHSR) should favor GHSR protective responses. To test this, we used rats with genetically enhanced GHSR sensitivity (Ghsr) and wild-type littermate controls and examined their acute responses to pharmacological challenges. Consistent with our hypothesis, Ghsr rats, despite normal glucose and insulin tolerance, exhibited a significant increase in blood glucose in response to GHSR agonism, accompanied by elevated counter-regulatory hormones including corticosterone. Concurrently, these rats displayed a notable decrease in locomotor activity and delayed feeding response. Also, GHSR agonism partially altered the cocaine-induced hyperlocomotion of Ghsr rats while they showed unaltered locomotor sensitization to cocaine. At the cellular level, functional studies indicated that the Ghsr mutation prolongs ghrelin-induced GHSR-G protein canonical signaling. Altogether, in a model of increased GHSR sensitivity, GHSR agonist stimulation was sufficient to promote a robust blood glucose increase, while the acute feeding response was delayed in a context of unexpected hypolocomotor response. This mechanism may have implications for severe states of undernutrition such as restrictive anorexia nervosa.
Relative and normalized iodine concentrations derived from photon counting computed tomography and their correlation with tumor grade and Ki67 in pancreatic neuroendocrine neoplasia: A pilot study.
Sähn MJ, Waltermann S, Ottemöller J … +7 more , Diallo-Danebrock R, Niehoff JH, Bähr M, Gerdes B, Borggrefe J, Begum N, Surov A
J Neuroendocrinol · 2026 Feb · PMID 41676873 · Full text
Neuroendocrine neoplasms are a rare and complex tumor entity, among which pancreatic neuroendocrine neoplasms generally display a more aggressive behavior. Despite a notable stage migration towards lower stages at initia...
Neuroendocrine neoplasms are a rare and complex tumor entity, among which pancreatic neuroendocrine neoplasms generally display a more aggressive behavior. Despite a notable stage migration towards lower stages at initial diagnosis, the incidence of pancreatic neuroendocrine neoplasms is rising. In recent publications, iodine concentration derived from dual energy computed tomography was explored as a potential biomarker for pancreatic neuroendocrine neoplasia tumor grade and Ki67. However, methodologies exhibited significant variability, and reported outcomes were ambiguous, ranging from weak correlations to strong predictive performance in complex multivariate analyses. With the advent of photon counting computed tomography and improved technical capabilities, this study revisits the topic and aims to provide evidence for tumor characterization using photon counting computed tomography-derived iodine concentration in pancreatic neuroendocrine neoplasms. Iodine concentration in neuroendocrine pancreatic primaries was analyzed in the portal venous phase regarding correlation with histopathological tumor grade and Ki67. Iodine concentration was normalized to aortic iodine concentration (normalized iodine concentration), as well as calculated relative to unaffected pancreatic tissue (relative iodine concentration). Correlations were analyzed using Spearman's rank correlation, and mean concentrations were analyzed using Mann-Whitney U test. Eighteen cases with pancreatic neuroendocrine neoplasms were included. Relative Iodine concentration exhibited a strong and statistically significant correlation with tumor grade (ρ = 0.54, p = 0.02) and Ki67 (ρ = 0.53, p = 0.02). Mean relative iodine concentration was higher in high-grade tumors (p = 0.02). Normalized iodine concentration showed weak, non-significant correlations with tumor grade (ρ = 0.33, p = 0.18) and Ki67 (ρ = 0.30, p = 0.22). Mean normalized iodine concentration did not differ significantly between low-grade and high-grade pancreatic NEN. Our preliminary results show that photon counting computed tomography derived iodine concentration and especially relative iodine concentration is a potential biomarker for tumor grade and Ki67 prediction with strong, statistically significant correlations in untreated pancreatic neuroendocrine neoplasms. The method is non-invasive, requires little to no additional resources and may support early, evidence-based therapeutic decisions even before primary tumor biopsy.
Response of gonadotropin-releasing hormone neurons from female mice to dynamic-clamp-simulated GABAergic conductances across development and after prenatal androgenization.
Jaime J, DeFazio RA, Moenter SM
J Neuroendocrinol · 2026 Feb · PMID 41652850 · Full text
Disrupted gonadotropin-releasing hormone (GnRH) secretion patterns can impair fertility as in polycystic ovary syndrome (PCOS).We used prenatally androgenized (PNA) female mice, which recapitulate neuroendocrine abnormal...
Disrupted gonadotropin-releasing hormone (GnRH) secretion patterns can impair fertility as in polycystic ovary syndrome (PCOS).We used prenatally androgenized (PNA) female mice, which recapitulate neuroendocrine abnormalities observed in PCOS patients, to study how changes in GnRH neuron intrinsic properties during development (prepubertal 3-week-old versus adult females) and with PNA treatment shape their postsynaptic response to GABAergic input. The properties of isolated GABAergic postsynaptic currents in GnRH neurons were used to generate representative model conductances of 1, 2, 5, and 10 nS, with decay time constants representing prepubertal and adult mice (7 vs. 10 ms). These conductances were applied to GnRH neurons from each experimental group using dynamic clamp, and response was measured. Neither development nor PNA altered the response of GnRH neurons to small conductances (1 or 2 nS), and these conductances did not initiate action potentials. In response to the 5 nS conductance, dynamic-clamp-induced postsynaptic potentials were larger in 3-week-old controls versus 3-week-old PNA mice at the 7 ms decay time constant and larger than vehicle-treated (VEH) adults at the 10 ms decay time constant. In response to larger conductances, only seven of 78 GnRH neurons from adults generated action potentials, whereas 14 of 73 GnRH neurons from 3-week-old females did. Interestingly, an altered action potential waveform was observed only in 3-week-old PNA females. The changes in GnRH neuron intrinsic properties occurring with development and PNA treatment result in differential responses to the same physiologic GABA input and may contribute to the action potential firing changes previously reported in this model.
Reproductive stress response in male black molly Poecilia sphenops: Evidence for receptor specific regulation by GABA.
Hotha A, Ganesh CB
J Neuroendocrinol · 2026 Feb · PMID 41652837 · Publisher ↗
Gamma-aminobutyric acid (GABA) is a primary inhibitory neurotransmitter involved in several physiological functions, including reproduction in vertebrates. However, its role in stress-induced reproductive modulation in v...
Gamma-aminobutyric acid (GABA) is a primary inhibitory neurotransmitter involved in several physiological functions, including reproduction in vertebrates. However, its role in stress-induced reproductive modulation in viviparous teleosts remains unclear. This study examined the receptor-specific GABAergic mechanisms influencing gonadal activity in response to stress in the black molly Poecilia sphenops. Four experiments were conducted. In the first experiment, fish were subjected to chronic intermittent stress, whereas in the second experiment, the effect of gabazine (a GABA receptor antagonist) and CGP-35348 (a GABA receptor antagonist) was assessed in unstressed and stressed fish. In the third and fourth experiments, the effect of GABA or GABA antagonists and agonists in vitro was examined in testicular tissues and interrenal tissues, respectively. Exposure to stress significantly elevated brain GABA levels and enhanced GABA immunoreactivity in the preoptic-hypothalamic-pituitary regions concomitant with a substantial increase in the whole-body and head kidney cortisol levels, but suppressed testicular spermatogenesis and steroidogenesis. In the second experiment, blockade of GABA receptors using gabazine effectively ameliorated stress-induced reductions in the testicular-somatic index, germ cell populations, and testicular 11-ketotestosterone (11-KT) levels, whereas GABA receptor blockade via CGP-35348 failed to restore these parameters. In the third experiment, treatment of GABA and GABA antagonists in vitro significantly increased 11-KT secretion in testicular tissues. Furthermore, selective receptor activation with muscimol (a GABA receptor agonist) and baclofen (a GABA receptor agonist) significantly enhanced cortisol secretion from the head-kidney, while gabazine and CGP-35348 suppressed cortisol production, indicating direct peripheral GABAergic modulation. These findings demonstrate a dual role for GABA in stress regulation, involving central activation of the GABAergic neuronal system and peripheral stimulation of cortisol secretion. The study provides novel insights into the GABA-mediated suppression of testicular spermatogenesis and steroidogenesis under stress, particularly through GABA receptors, and suggests that pharmacological antagonism of GABA receptors may help mitigate stress-induced reproductive dysfunction in viviparous teleosts.
A new, machine learning-based approach to metastatic neuroendocrine tumors of unknown origin.
Lü J, Amin T, Clauditz T … +8 more , Steinkraus K, Buchstab O, Huber S, Izbicki J, Fründt T, Schrader J, Werner R, Schmitz R
J Neuroendocrinol · 2026 · PMID 41652828 · Full text
Neuroendocrine tumors (NETs) frequently present at a metastatic stage, particularly with liver metastases. Identifying the site of the primary tumor is critical for guiding therapy but often proves difficult. Small intes...
Neuroendocrine tumors (NETs) frequently present at a metastatic stage, particularly with liver metastases. Identifying the site of the primary tumor is critical for guiding therapy but often proves difficult. Small intestine NETs are especially distinct in their prognosis and treatment. To address this challenge, we developed a novel, machine learning-based tool to predict the site of origin-specifically small intestine or pancreas-using routine hematoxylin and eosin (H&E)-stained slides from hepatic metastases. To avoid mislabeling in the clinically relevant scenario of any possible tumor origin, the method applies a two-step approach with optional abstention for uncertain classifications or non-small intestine/non-pancreas cases. In a retrospective, clinically realistic cohort with unrestricted tumor origin, the model identified small intestine NETs with a sensitivity of 71.4% at 100% specificity and positive predictive value (PPV), and high negative predictive value. A relevant subset of pancreatic NETs can also be reliably detected (sensitivity 33.3%, specificity 94.1%, PPV 85.7%). Generalizability and robustness were rigorously validated on an external dataset using different scanners, institutions, and resection techniques. The tool is intended as an additional method where other diagnostic modalities remain inconclusive regarding the location of the primary tumor. To facilitate further research and clinical translation, all models and extracted features are publicly released.
Glucocorticoids and cell fate in the developing brain: Neuroendocrine mechanisms shaping developmental trajectories.
Eachus H
J Neuroendocrinol · 2026 Feb · PMID 41649042 · Full text
Early life stress (ELS) is a major risk factor for later psychiatric and neurological disorders. Glucocorticoids (GCs), the hormonal end-products of the neuroendocrine stress response, are central mediators of this risk,...
Early life stress (ELS) is a major risk factor for later psychiatric and neurological disorders. Glucocorticoids (GCs), the hormonal end-products of the neuroendocrine stress response, are central mediators of this risk, influencing how the developing brain grows and adapts. Research has shown that GCs affect processes such as cell proliferation, neuronal survival, and maturation, but much less attention has been given to whether they also shape cell fate-the developmental choices that determine whether stem and progenitor cells give rise to neurons, astrocytes, oligodendrocytes, or other specialised lineages. In this perspective, I argue that cell fate provides a valuable new lens for understanding how stress becomes embedded in brain architecture. Because GCs act directly on neural stem and progenitor populations, it is plausible that their influence extends beyond the quantity of cells produced, to the identities that emerge. I outline an initial framework for interpreting potential effects of GCs on fate, review emerging evidence from different model systems, and consider mechanisms by which stress hormones could alter developmental trajectories. By focusing on fate, this article highlights a novel dimension of neuroendocrine influence on brain development, with implications for how early experiences confer vulnerability, or resilience, to later mental health outcomes.
Dense sampling for mapping pituitary growth dynamics before, during, and after pregnancy.
Picci G, Arora R, Grotzinger H … +5 more , Jordan K, Pritschet L, Chrastil ER, Jacobs EG, Rasmussen JM
J Neuroendocrinol · 2026 Feb · PMID 41644106 · Full text
Pregnancy represents a period of profound endocrine activity and neural reorganization. While recent evidence highlights pituitary volume as a biomarker of endocrine dynamics during pregnancy, its precise trajectory (tim...
Pregnancy represents a period of profound endocrine activity and neural reorganization. While recent evidence highlights pituitary volume as a biomarker of endocrine dynamics during pregnancy, its precise trajectory (timing and relative magnitude of effect) across human pregnancy remains undescribed. Three healthy women (59 total observations) underwent T1-weighted MRI before conception (5 baseline observations), during pregnancy (38 total observations, spanning gestational weeks 1-36), and up to 1 year postpartum (16 total observations). Anterior and posterior pituitary lobes were manually delineated at every visit. A longitudinal pipeline co-registered each scan to all other intra-subject scans, propagated their labels, and generated majority-vote ensembles for objective and regularized volume estimates. Person-centered z-scores were computed, and generalized additive mixed models (GAMMs) with random intercepts estimated nonlinear volume trajectories. The anterior lobe followed a nonlinear trajectory, with gestational age explaining 73% of adjusted variance in anterior-pituitary volume (edf = 7.59, F = 20.2, p < 10). Specifically, volume exhibited a modest first trimester decrease (local fit minima: -0.9 SD at 10.6 weeks), followed by a steep rise into the 3rd trimester (local fit maxima: +1.8 SD at 34.1 weeks, or ~ 17.5% increase from 1st trimester minima, by volume), before returning to baseline near 3 months postpartum. Sensitivity analyses restricted to linear regression during early (-5 to 12 weeks) and late (12 to 40 weeks) windows replicated the observed non-linear decreasing/increasing slopes (β = -0.09 SD/week, p = 0.036; β = 0.14 SD/week, p < 10). In contrast, no significant volumetric changes in the posterior lobe were detected across the observation period (p = 0.79). In one of the first studies of its kind to leverage a dense sampling approach in multiple pregnant women, non-linear analyses revealed rapid, reversible anterior pituitary hypertrophy across human pregnancy consistent with lactotrope expansion and heightened endocrine load.
Determinants of incidence trends in pancreatic neuroendocrine neoplasms.
Lamberti G, Andrini E, Di Odoardo A … +3 more , Zappi A, Ricci C, Campana D
J Neuroendocrinol · 2026 Feb · PMID 41634999 · Full text
The incidence of pancreatic neuroendocrine neoplasms (NENs) is rising; whether this reflects a true increase in disease occurrence or improved detection remains uncertain. We conducted a retrospective, population-based s...
The incidence of pancreatic neuroendocrine neoplasms (NENs) is rising; whether this reflects a true increase in disease occurrence or improved detection remains uncertain. We conducted a retrospective, population-based study using data from the Surveillance, Epidemiology, and End Results (SEER) Program (1975-2021) to examine temporal trends in the incidence of pancreatic NENs and assess whether changes reflect improved detection versus a true increase. Incidence trends were stratified by demographic and socioeconomic proxies of healthcare access, including income, residential setting, and race as recorded in SEER at the county level. We identified 16,253 cases of pancreatic NENs (44.6% women; median age 62 years). Incidence increased 7.75-fold between 1975 and 2021, rising from 0.21 cases per 100,000 population in 1975 to 1.58 per 100,000 in 2021. Median tumour size at diagnosis decreased significantly, with an average annual reduction of 0.73 mm (R = 0.765; p < 0.001). After adjustment, incidence increased more steeply among men, individuals aged 40-65 years and >65 years (vs. <40 years), those recorded as White (vs. Black and other races), individuals with higher income, and those residing in urban (vs. rural) counties. Incidence also rose more steeply for tumours located in the pancreatic tail, for grade 1 tumours (vs. grades 2 and 3), and for smaller tumours (vs. larger ones). The rising incidence of pancreatic NENs is probably explained by improved detection, particularly among populations with greater access to healthcare, rather than by a true increase in disease occurrence.
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