Journal Of Neuroendocrinology[JOURNAL]
Sun
200 papers
Three-dimensional quantification of oxytocin neurons in the hypothalamic paraventricular nucleus reveals sex- and subregion-specific differences in two genetic mouse models of autism.
Patwardhan A, Li S, Chen J … +1 more , Choe KY
J Neuroendocrinol · 2025 Dec · PMID 40984661 · Full text
Oxytocin (OXT), a neuropeptide hormone essential to a wide range of social functions, has drawn increasing attention as a crucial contributor to the neurobiology of autism spectrum disorder (ASD). Central OXT system disr...
Oxytocin (OXT), a neuropeptide hormone essential to a wide range of social functions, has drawn increasing attention as a crucial contributor to the neurobiology of autism spectrum disorder (ASD). Central OXT system disruptions have been reported in several genetic mouse models of ASD; however, a detailed and systematic characterization of these phenotypes, and cross-model identification of shared and distinct features, are presently lacking. We integrated whole-brain OXT immunolabeling, SHIELD tissue clearing, light-sheet microscopy, and three-dimensional (3D) machine learning-based cell detection to establish a high-throughput, intact-tissue pipeline and quantified OXT immunopositive (OXT+) neurons across subregions of the paraventricular nucleus of the hypothalamus (PVN) in two genetic mouse models of ASD: Cntnap2 and Fmr1 knockout (KO) mice. We validated this pipeline alongside conventional immunohistochemistry using tissue sections. We show subregion- and sex-specific differences in PVN OXT+ cell counts in the two KO models. Notably, whole-PVN analysis revealed additional subregion- and sex-specific differences that were not evident in section-based quantification. These results identify subregion- and sex-specific differences in PVN OXT+ neuronal distribution as a shared phenotype in two genetic mouse models of ASD. This work highlights the importance of region-specific, high-resolution 3D approaches in intact tissue for quantifying cell populations within anatomically complex brain regions.
Annual rhythms of thyroid hormone signaling: Environmental influences on thyroid function and disease implications.
Liu J, Wang Z, Wang H … +3 more , Yu L, Yu Y, Sun H
J Neuroendocrinol · 2025 Nov · PMID 40954013 · Publisher ↗
Hormones within the hypothalamic-pituitary-thyroid (HPT) axis play a central role in acclimatization, dynamically responding to nutritional, thermal, and photoperiodic cues to coordinate metabolic, thermoregulatory, and...
Hormones within the hypothalamic-pituitary-thyroid (HPT) axis play a central role in acclimatization, dynamically responding to nutritional, thermal, and photoperiodic cues to coordinate metabolic, thermoregulatory, and reproductive functions. Abundant food elevates thyroid hormone (TH), driving energy storage and foraging behaviors, while scarcity reduces TH levels, inducing energy-saving states like hypometabolism or hibernation, in which TH-leptin crosstalk is important. Cold exposure upregulates TH to enhance mitochondrial thermogenesis, with TH acting as a pivotal mediator in the coordination between the hypothalamic thermoregulatory center and peripheral organs. The photoperiodic response converges evolutionarily on the TSH-DIO2-T3 axis, modulating seasonal GnRH release for seasonal reproductive activity. Humans display an annual rhythm of HPT-axis hormones, characterized by winter TSH elevation with TH variability, which affects thyroid dysfunction diagnosis and necessitates seasonally adjusted therapies. Extreme natural environmental stressors and modern environmental changes can profoundly disrupt this acclimatization to decompensate into a pathophysiological state. Meanwhile, thyroid diseases like hypo- and hyperthyroidism show seasonal patterns of disease onset and exacerbation, indicating that the environment impacts disease progression. Thus, cross-species analysis of seasonal dynamics of TH signaling can enhance our understanding of environmental impacts on thyroid function and inform therapeutic strategies aligned with endogenous annual rhythms to optimize the management of thyroid disorders.
Controversies in NEN: An ENETS position statement on the management of locally advanced neuroendocrine neoplasia of the small intestine and pancreas without distant metastases.
Tesselaar MET, Partelli S, Braat AJAT … +7 more , Croitoru A, Soares Santos AP, Schrader J, Welin S, Christ E, Falconi M, Bartsch DK
J Neuroendocrinol · 2025 Dec · PMID 40948187 · Publisher ↗
Locally advanced neuroendocrine neoplasms (NENs) are defined by extensive local invasion in the absence of distant metastases, although specific definitions may vary among study groups. While most patients with NENs pres...
Locally advanced neuroendocrine neoplasms (NENs) are defined by extensive local invasion in the absence of distant metastases, although specific definitions may vary among study groups. While most patients with NENs present with localized or metastatic disease, a smaller subset is diagnosed with locally advanced tumors. Management of this subgroup remains particularly challenging, owing to the limited evidence base and lack of consensus regarding optimal therapeutic strategies. This guidance document synthesizes the current evidence and expert knowledge on the management of locally advanced NENs of the small intestine and pancreas, addressing four clinically relevant key questions that aim to inform best practice in these patients.
Cellular mechanisms of long-term osmoregulation in magnocellular neurons.
Haan KD, Fisher TE
J Neuroendocrinol · 2025 Dec · PMID 40936216 · Full text
Osmoregulation is an essential homeostatic process that maintains the osmolality of the extracellular fluid (ECF) close to a physiological setpoint. Vasopressin (VP) plays a key role in osmoregulation and is secreted by...
Osmoregulation is an essential homeostatic process that maintains the osmolality of the extracellular fluid (ECF) close to a physiological setpoint. Vasopressin (VP) plays a key role in osmoregulation and is secreted by the magnocellular neurosecretory cells (MNCs) of the hypothalamus. MNC electrical activity and VP release increase with elevations of ECF osmolality. MNC osmosensitivity depends on a mechanosensitive N-terminal variant of the transient receptor potential vanilloid type 1 (ΔN-TRPV1) channel that activates in response to osmotically induced cell shrinkage. ΔN-TRPV1 mechanosensitivity depends on their association with microtubules in the MNC cytoskeleton and is modulated by a dense layer of submembranous actin in MNC somata. MNCs exposed to sustained increases in osmolality, however, undergo marked somatic hypertrophy, which suggests that other mechanisms may be important to maintain VP release. Recent evidence suggests that the translocation of ΔN-TRPV1 (and possibly other channels) to the MNC cell surface could contribute to osmotically induced long-term increases in MNC excitability. Osmotically induced ion channel translocation is dependent on MNC firing, Ca influx through L-type Ca channels, the activation of phospholipase C δ1 and protein kinase C, and soluble N-ethylmaleimide-sensitive factor attachment protein receptor-dependent exocytotic fusion. Other recent work has explored osmotically induced changes in the MNC cytoskeleton that may be related to hypertrophy and ion channel translocation. MNCs may also be activated by elevations in extracellular Na through the activation of the Na-sensitive Na channel, Na. This review highlights recent advancements in our understanding of long-term MNC regulation at the cellular level.
Benzophenones: How ultraviolet filters can interfere with reproduction.
Gomez JMR
J Neuroendocrinol · 2025 Dec · PMID 40930767 · Publisher ↗
Benzophenones (BPs) are widely used as ultraviolet (UV) filters in personal care products, plastics, and food packaging. Although they serve as effective photoprotective agents, growing evidence suggests that BPs can act...
Benzophenones (BPs) are widely used as ultraviolet (UV) filters in personal care products, plastics, and food packaging. Although they serve as effective photoprotective agents, growing evidence suggests that BPs can act as endocrine-disrupting chemicals (EDCs), interfering with hormone regulation and reproductive functions. This review summarizes the current knowledge on BP exposure, metabolism, and their potential effects on reproductive health. We discuss the mechanisms by which BPs interact with hormonal receptors, alter steroid metabolism, and influence the hypothalamic-pituitary-gonadal axis. Special attention is given to BP-2 and BP-3, which have been detected in human biological samples, including urine, blood, and fetal tissues. Additionally, we highlight recent findings from in vitro and in vivo studies demonstrating their estrogenic activity and potential impact on reproduction. The review also addresses regulatory concerns, emphasizing the need for stricter policies to limit human and environmental exposure to BPs. Understanding the effects of these chemicals is essential for assessing their safety and developing alternatives to mitigate potential health risks.
Mechanisms of intrinsic osmolality and sodium detection by magnocellular neurosecretory neurons.
Salgado-Mozo S, Murtaz A, Wyrosdic JC … +4 more , O'Reilly-Fong J, Zaelzer C, LaPierre MP, Bourque CW
J Neuroendocrinol · 2025 Dec · PMID 40925856 · Full text
The maintenance of extracellular fluid (ECF) osmolality and sodium concentration ([Na]) near optimal "set point" values sustains physiological functions and prevents pathological states such as hypo- and hypernatremia. T...
The maintenance of extracellular fluid (ECF) osmolality and sodium concentration ([Na]) near optimal "set point" values sustains physiological functions and prevents pathological states such as hypo- and hypernatremia. The peptide hormones vasopressin (antidiuretic hormone) and oxytocin (a natriuretic hormone in rats) play key roles in this process. These hormones are synthesized by hypothalamic magnocellular neurosecretory cells (MNCs) that project to the neurohypophysis and are released into the systemic circulation in response to rises in ECF osmolality or [Na]. These homeostatic responses are highly sensitive. For example, vasopressin release is elicited by an increase in ECF osmolality as small as ≥1%. The osmotic and sodium-dependent control of vasopressin and oxytocin release at the neurohypophysis is directly regulated by the electrical activity of MNCs. This regulation involves an array of mechanisms that include synaptic inputs from the brain and periphery, the effects of chemicals released by glial cells, and intrinsic sensory properties of MNCs. These overlapping mechanisms may offer an important degree of redundancy for the homeostatic control of vasopressin and oxytocin release and contribute to the high sensitivity of these responses. Recent work has shown that the intrinsic sodium sensitivity and osmosensitivity of MNCs play an important role in the control of these neurons in vivo. This review provides an update of our current understanding of the molecular and cellular mechanisms that contribute to the cell-autonomous sensory properties of MNCs.
Oxytocin neural responses distinguish social novelty from familiarity but not kin from non-kin in male spiny mice.
Esquilin-Rodriguez CJ, Fricker BA, Kelly AM
J Neuroendocrinol · 2025 Dec · PMID 40921445 · Publisher ↗
In most species, individuals must be able to identify threats, peers, and potential mates to survive. The distinction of kin from non-kin and novel conspecifics from familiars is essential to the successful categorizatio...
In most species, individuals must be able to identify threats, peers, and potential mates to survive. The distinction of kin from non-kin and novel conspecifics from familiars is essential to the successful categorization of these identities. Although oxytocin (OXT) signaling has been implicated in social recognition, little is known about the contributions of distinct OXT-producing cell groups to distinguishing conspecific type. To determine whether OXT-producing neuronal populations differentially respond to novelty or kinship status, we conducted immediate early gene tests in male spiny mice (Acomys dimidiatus), a communally breeding species that we previously showed distinguishes between novelty and kinship status. Immunohistochemical analysis of brain tissue revealed that the OXT cell populations in the paraventricular nucleus of the hypothalamus and the anterior hypothalamus did not differentially respond to the kinship or novelty status of same-sex conspecifics. However, while OXT-producing neurons in the bed nucleus of the stria terminalis did not distinguish between kin and non-kin spiny mice, this cell group was more responsive to familiar than novel conspecifics. These results suggest that extrahypothalamic OXT neurons may be involved in aspects of processing the novelty status of a conspecific.
Sleep in neurodegenerative diseases: A focus on melatonin, melanin-concentrating hormone and orexin.
Guillot SJ, Luppi PH, Dupuis L … +1 more , Bolborea M
J Neuroendocrinol · 2025 Nov · PMID 40887101 · Full text
Sleep and circadian rest-activity rhythm alterations are recognised as inherent clinical features of various neurodegenerative diseases. Traditionally viewed as secondary manifestations of neurodegeneration, recent studi...
Sleep and circadian rest-activity rhythm alterations are recognised as inherent clinical features of various neurodegenerative diseases. Traditionally viewed as secondary manifestations of neurodegeneration, recent studies have revealed that disruptions in circadian rhythm and sleep-wake cycles can precede clinical symptoms and significantly contribute to the underlying pathophysiological progression. In this review, we summarise recent research on the impact of sleep and circadian rhythm alterations in ageing and major neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and frontotemporal dementia, highlighting the roles of melatonin, orexin, and melanin-concentrating hormone (MCH) systems as key regulators at the intersection of sleep and neurodegeneration. We argue that sleep and circadian alterations may serve as early biomarkers and therapeutic targets for these diseases.
Artificial intelligence in the diagnosis of gastro-entero-pancreatic neuroendocrine neoplasms: Potential benefits and current limitations.
Merola E, Fanciulli G, Pes GM … +1 more , Dore MP
J Neuroendocrinol · 2025 Nov · PMID 40876862 · Publisher ↗
Neuroendocrine neoplasms (NENs), once considered rare, are now increasingly diagnosed worldwide, with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) accounting for the majority of cases (55%-70%). NENs are cha...
Neuroendocrine neoplasms (NENs), once considered rare, are now increasingly diagnosed worldwide, with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) accounting for the majority of cases (55%-70%). NENs are characterized by considerable heterogeneity, driven by factors such as tumor differentiation, Ki-67 index, primary tumor location, somatostatin receptor status, and disease stage. International guidelines advocate for a multidisciplinary approach to ensure individualized treatment strategies. Given the disease's complexity, artificial intelligence (AI) may offer substantial support in the management of NENs. AI is playing an increasingly prominent role in medicine by enabling advanced diagnostic capabilities through machine learning and deep learning algorithms, particularly in imaging. However, current literature on AI applications in NENs is limited, and their routine use in clinical practice has yet to be established. This narrative review aims to provide a comprehensive overview of the potential roles of AI in the diagnosis of GEP-NENs, while also addressing the associated biases and ethical considerations of medical AI implementation.
Comparative analysis of androgen and estrogen receptor mRNA expression in adult mouse hippocampus.
Schöbe M, Brunne B, Bender RA
J Neuroendocrinol · 2025 Nov · PMID 40874290 · Full text
In hippocampus, androgens and estrogens influence neuronal plasticity via a range of nuclear or membrane-bound receptors. While much work has focused on determining their functions, a certain vagueness about the cellular...
In hippocampus, androgens and estrogens influence neuronal plasticity via a range of nuclear or membrane-bound receptors. While much work has focused on determining their functions, a certain vagueness about the cellular expression of established receptors has remained. Moreover, novel candidates, such as the androgen-responsive zinc-transporter ZIP9, need to be inserted into the emerging picture. We used highly-sensitive RNAscope in situ hybridization and quantitative real-time PCR to examine the cellular and total hippocampal mRNA expression of androgen (AR, ZIP9) and estrogen receptors (ERα, ERβ, GPER1) in adult mouse hippocampus, considering sex and estrous cycle as variables. (1) Androgen receptors are more abundantly expressed than estrogen receptors. (2) AR and ZIP9 mRNA regularly co-localize in hippocampal neurons, but ZIP9 mRNA is more homogenously distributed and also expressed in astrocytes and microglia. (3) ERα and GPER1 are the predominant estrogen receptors (ERβ mRNA was very low), but exhibit differential expression patterns: GPER1 mRNA is preferentially expressed in glutamatergic neurons, while ERα is specifically expressed in a subpopulation of GABAergic interneurons. Both receptors were barely detectable in astrocytes and microglia. (4) ZIP9 mRNA expression varies during the estrous cycle, being significantly down-regulated if serum E2 is high, whereas ERα mRNA expression was generally higher in females. We provide a comprehensive cellular and quantitative expression analysis of androgen and estrogen receptors in adult mouse hippocampus, including for the first time mRNA expression data on ZIP9. Our data underline the necessity to consider sex and estrous cycle when studying sex hormone functions.
Corticotropin-releasing factor type 1 receptors in the rat nodose ganglion are involved in the transduction of stress-induced visceral sensory signals to the brain.
Mano-Otagiri A, Shibasaki T, Sakai A … +1 more , Kakinuma Y
J Neuroendocrinol · 2025 Nov · PMID 40840873 · Full text
Corticotropin-releasing factor (CRF) plays roles in stress-related responses through its type 1 (CRF) and type 2 receptors. Both CRF and CRF are expressed in the rat colon. Peripheral CRF administration and various stres...
Corticotropin-releasing factor (CRF) plays roles in stress-related responses through its type 1 (CRF) and type 2 receptors. Both CRF and CRF are expressed in the rat colon. Peripheral CRF administration and various stressors increase colonic motility and defecation. Stress induces CRF release in the colon, suggesting CRF may mediate stress-related responses of the colon. The vagal nodose ganglion (NG) transduces visceral information, including colonic sensation, to the brain. However, it remains unclear whether the CRF/CRF system is involved in vagal afferent functions. This study, therefore, aimed to clarify the involvement of the CRF/CRF system in relaying visceral sensory information to the brain and the effect of stress exposure on vagal nerve function. The experiments were conducted in male rats. First, CRF-like immunoreactivity (CRF-LI) was characterized in the NG. Second, the effects of vagotomy on CRF-LI in the NG, intraperitoneally administered CRF-induced fecal output, and c-Fos expression in the nucleus tractus solitarius (NTS) were evaluated. Subsequently, a fast blue retrograde tracer was microinjected into the proximal colon. Finally, we analyzed CRF- or stress-induced phosphorylation of cyclic AMP-response element-binding protein (pCREB) in the NG. CRF mRNA and CRF-LI were detected, and CRF-LI accumulated on the proximal side of the ligated region of the nerve trunk, and CRF-LI was detected in most cholinergic neurons. CRF siRNA suppressed the expression of CRF-LI in the NG. Subdiaphragmatic vagotomy decreased the number of CRF-positive cells in the NG while it did not affect CRF-induced fecal output. CRF-induced c-Fos expression in the NTS was suppressed by vagotomy. A neuronal tracing study showed that approximately half of CRF-positive cells expressed fast blue in the NG. Intraperitoneal CRF, a selective CRF agonist, or immobilization stress induced pCREB expression and increases in CRF-positive cells in the NG. In contrast, a CRF antagonist reduced the immobilization-induced increase in the expression of pCREB in the NG. These results suggest that the CRF/CRF system is involved in the signal transduction of colonic sensory information to the central nervous system via the NG.
Intraoperative hepatic ultrasonography in patients with gastrointestinal and pancreatic neuroendocrine neoplasms without preoperative evidence of liver metastases.
Viganò L, Maruccio M, Faustini F … +18 more , Frigerio I, Gavazzi F, De Robertis Lombardi R, Scopelliti F, Capretti G, Ammirabile A, D'Onofrio M, Giardino A, Ferrillo G, Rodari M, Regi P, Procopio F, Salvia R, Lania A, Butturini G, Landoni L, Torzilli G, Zerbi A
J Neuroendocrinol · 2025 Nov · PMID 40825538 · Full text
In patients with gastroenteric and pancreatic neuroendocrine neoplasms (GEP-NENs), the risk of liver metastases is high, but the accuracy of standard imaging for detecting small hepatic nodules is limited. This raises co...
In patients with gastroenteric and pancreatic neuroendocrine neoplasms (GEP-NENs), the risk of liver metastases is high, but the accuracy of standard imaging for detecting small hepatic nodules is limited. This raises concerns about the adequacy of staging in cM0 patients. This study aims to determine the percentage of cM0 GEP-NEN patients with occult liver metastases that can be identified using intraoperative ultrasound (IOUS) during surgery for the primary tumor. A prospective study was conducted at three high-volume centers between October 2020 and December 2023. Patients who underwent surgery for GEP-NENs staged as cM0 based on CT and PET/CT (MRI in selected cases) were included. IOUS was systematically performed, in combination with contrast-enhanced IOUS (CE-IOUS) and biopsy when necessary. The ground truth was the result of a contrast-enhanced CT or MRI performed 6 months after surgery. A total of 51 cM0 GEP-NEN patients were enrolled. IOUS detected suspicious liver nodules in seven patients (14%). Three were classified as metastatic based on the IOUS pattern, CE-IOUS pattern, and biopsy, respectively, while four were classified as non-metastatic based on biopsy (n = 2) or CE-IOUS pattern (n = 2). At six-month follow-up imaging, two patients (4%) were confirmed as metastatic (the suspicious metastasis at CE-IOUS was not confirmed). GEP-NENs G3 and those with necrosis had a higher risk of metastases (one-third of patients, p < 0.05 compared to G1-2 and non-necrotic neoplasms). IOUS, combined with CE-IOUS and biopsy, achieved 100% sensitivity, 98% accuracy, and 100% negative predictive value. IOUS, along with CE-IOUS and biopsy, provides accurate staging in GEP-NENs, identifying occult metastases in approximately 4% of cM0 cases. Due to the low incidence of occult metastases, routine use of IOUS cannot be recommended. It should be considered selectively in aggressive tumors, which have shown a significantly higher risk of liver involvement.
Single-cell transcriptomic analysis reveals a metastasis-associated PCSK1 neuroendocrine subpopulation in pancreatic neuroendocrine tumors.
Yin X, Li X, Mi L … +2 more , Hou J, Yin F
J Neuroendocrinol · 2025 Nov · PMID 40817830 · Publisher ↗
Pancreatic neuroendocrine tumors (PNETs) are uncommon malignancies characterized by significant clinical heterogeneity and a pronounced tendency for liver metastasis. Despite this, the cellular mechanisms driving PNET pr...
Pancreatic neuroendocrine tumors (PNETs) are uncommon malignancies characterized by significant clinical heterogeneity and a pronounced tendency for liver metastasis. Despite this, the cellular mechanisms driving PNET progression remain inadequately elucidated, especially concerning neuroendocrine subpopulations. We analyzed publicly available single-cell RNA sequencing (scRNA-seq) data from 27 samples, including adjacent normal tissues (NT), primary tumors (PT), and hepatic metastases (HM), to explore the heterogeneity of neuroendocrine cells. Our downstream analyses encompassed copy number variation (CNV) inference, pseudotime trajectory modeling using CytoTRACE2 and Monocle3, Single-Cell Regulatory Network Inference and Clustering (SCENIC), cell-cell communication analysis via CellChat, and external validation with bulk RNA-seq datasets. We identified a distinct PCSK1 neuroendocrine cell subpopulation, predominantly found in HM, which exhibited a high CNV burden, low differentiation potential, and significant transcriptional divergence from the NEUROD1 neuroendocrine cells prevalent in primary tumors. The trajectory analysis delineated a developmental continuum commencing from the NEUROD1 subpopulation and culminating in the PCSK1 subpopulation. SCENIC analysis identified ATF6 as a pivotal transcriptional regulator within the PCSK1 subpopulation, while KEGG enrichment of its target genes indicated involvement in stress-related signaling pathways. Furthermore, cell-cell communication analysis demonstrated that fibroblasts were the predominant signaling source to the PCSK1 subpopulation in both primary tumors (PT) and hepatic metastases (HM), with conserved ligand-receptor interactions, including the CD99-CD99 and collagen-integrin axes. Our study identifies a metastasis-enriched, terminally differentiated PCSK1 subpopulation and elucidates its potential regulatory and microenvironmental characteristics. These findings enhance our understanding of the cellular states linked to the progression of PNETs and lay the groundwork for subsequent mechanistic investigations.
Association rule mining of clinical and biomarker data in neuroendocrine tumors: A prospective study on disease progression.
Knigge UP, Kjellman M, Grønbæk H … +7 more , Thiis-Evensen E, Schalin-Jäntti C, Welin S, Sørbye H, Schneider MDP, Belusa R, Nordic NET Biomarker Group
J Neuroendocrinol · 2025 Oct · PMID 40812788 · Full text
There is an unmet need for new methods to predict disease course in patients with neuroendocrine tumors (NET). We investigated 92 putative cancer-related plasma proteins including chromogranin A (CgA) and clinical parame...
There is an unmet need for new methods to predict disease course in patients with neuroendocrine tumors (NET). We investigated 92 putative cancer-related plasma proteins including chromogranin A (CgA) and clinical parameters at the time of diagnosis to identify early factors associated with progressive (PD) or stable disease (SD). Patients with NET grade 1 and 2 of the small intestine (siNET) and pancreas (pNET) were included in this prospective study. Blood samples were obtained at the time of diagnosis before tumor-related therapy was initiated. During 3 years of follow-up, SD or PD was determined according to current clinical practice by each investigator. Association rule mining (ARM) was used to identify combinations of biomarkers and clinical parameters associated with SD or PD. Altogether, 115 patients with siNET and 30 with pNET with complete clinical and biomarker data were included in the analysis representing 3 years of follow-up. Several novel plasma proteins and clinical factors were associated with either PD or SD. In siNET, CgA (>4 upper limits of normal [ULN]) was the most frequent biomarker associated with PD. Females, in contrast to males, with CgA >4 ULN showed a high risk of progression (PPV 100%, NPV 63%). In the siNET cohort, Carboxypeptidase E (CPE) was a discriminating factor between SD and PD. CPE <3.03 was associated with SD, whereas CPE >3.14 was associated with PD (p = 0.003). In the pNET cohort, among clinical variables, only the presence of liver metastasis was associated with PD. CgA was not among the top biomarkers associated with PD. Several parameters, both clinical and biomarker data, as well as combinations of these, were associated with PD or SD 3 years after diagnosis. We identified novel biomarkers improving the association with PD or SD. [Correction added on 28 August 2025, after first online publication: Abstract has been updated.].
Quality of life as a predictor for survival in patients with small intestinal neuroendocrine tumours.
Ohlsson H, Nilsson M, Sundlöv A … +2 more , Malmström M, Almquist M
J Neuroendocrinol · 2025 Nov · PMID 40796203 · Full text
Health-related quality of life (HRQoL) has been shown to predict overall survival (OS) in several different malignancies, but not in patients with small intestinal neuroendocrine tumours (siNET). We evaluated the influen...
Health-related quality of life (HRQoL) has been shown to predict overall survival (OS) in several different malignancies, but not in patients with small intestinal neuroendocrine tumours (siNET). We evaluated the influence of HRQoL on survival in patients with siNET. We included 85 patients with advanced siNET who completed the validated HRQoL instruments, EORTC QLQ-C30 and GI.NET21. We used Cox proportional hazards to calculate the hazard ratio (HR) of survival according to the QLQ-C30 summary score, adjusting for clinical variables selected with causal inference. Flexible parametric modelling using cubic splines was used to illustrate the time-dependent relationship between HRQoL and OS. The QLQ-C30 summary score was correlated with overall survival (OS) with an adjusted HR of 0.62 (95% CI 0.46-0.83, p < .001) for each 10-point increase in summary score. Compared to a model using only clinical variables, the summary score increased predictive accuracy by eight percentage units and improved model fit. The inclusion of GI.NET21 with the summary score yielded similar results. HRQoL predicts overall survival in patients with siNET, providing additional information to clinical variables. Measuring HRQoL might be useful when following patients with siNET.
Tumor-infiltrating immune cells predict the response to somatostatin receptor ligands only in somatotropinomas naïve to medical therapy.
Chiloiro S, Vicari A, Giampietro A … +14 more , Mattogno PP, Cappoli N, Konini G, Calandrelli R, Lauretti L, Gaudino S, Rigante M, Rindi G, Olivi A, De Marinis L, Bianchi A, Doglietto F, Gessi M, Pontecorvi A
J Neuroendocrinol · 2025 Nov · PMID 40789673 · Full text
Tumor-infiltrating immune cells (TICs) are important components of the tumor microenvironment (TME). They regulate somatotroph adenoma treatment responses to therapy with somatostatin receptor ligands (SRLs), mediated by...
Tumor-infiltrating immune cells (TICs) are important components of the tumor microenvironment (TME). They regulate somatotroph adenoma treatment responses to therapy with somatostatin receptor ligands (SRLs), mediated by soluble factors and cytokines. In this study, we assessed the effect of SRLs treatment on TICs. A retrospective and observational study was performed on acromegaly patients to compare the number of TICs in 75 patients naïve to SRL before surgery and in 33 patients treated with SRL for at least 6 months before surgery. In SRLs-naive patients at surgery, the CD68+/CD8+ ratio was higher in invasive tumors (4.9, IQR: 14, p = .028) than in non-invasive tumors (4.3, IQR: 4.2) as well as in patients not responsive to post-surgical/adjuvant treatment with SRLs (7.5, IQR: 13, p = .006) than those responsive to treatment (3.4, IQR: 3.2). In patients treated with SRLs before surgery, the number of CD68+ macrophages and the ratio CD68+/CD8+ were lower in patients non-responsive to post-surgery/adjuvant SRL treatment (CD68+: 48/HPFs, IQR: 22.9, p = .005; CD68+/CD8+: 2.0, IQR: 3.6, p = .05) than in responsive patients (CD68+: 80/HFPs, IQR: 51, CD68+/CD8+: 5, IQR: 5.6). Higher CD68+/CD8+ ratio was an independent risk factor for post-surgery SRL treatment resistance, only in patients naïve to SRLs at surgery (OR: 4.3, 95% IC: 1.4-12.9, p = .006). Our results indicate a presurgical SRL therapy interplay with TICs in somatotroph adenomas and show that the CD68+/CD8+ ratio is a biomarker for treatment resistance in SRL-naïve patients. CLINICAL TRIAL REGISTRATION: The Clinical Trial Registration number is 5116.
Melatonin receptors and thyroid stimulating hormone in the equine pars tuberalis: Potential modulators of seasonal reproduction in the mare.
Bailey VN, Gilbert BM, Vetter M … +1 more , Oberhaus EL
J Neuroendocrinol · 2025 Oct · PMID 40785101 · Publisher ↗
The mechanism by which photoperiod influences the hypothalamic-pituitary-gonadal (HPG) axis and regulates seasonal reproduction in horses has yet to be fully elucidated. The hypophyseal pars tuberalis (PT) has been indic...
The mechanism by which photoperiod influences the hypothalamic-pituitary-gonadal (HPG) axis and regulates seasonal reproduction in horses has yet to be fully elucidated. The hypophyseal pars tuberalis (PT) has been indicated as a critical site for the transduction of melatonin signals through melatonin-responsive, PT-specific cells that produce thyroid-stimulating hormone (TSH) in many mammalian species. However, this has yet to be investigated in horses. The objective of this study was to explore the interaction of melatonin and thyroid-stimulating hormone in the equine HPG axis. Pituitaries from mares of light-horse breeds (Quarter Horse, Thoroughbred, etc.) categorized as either breeding season or non-breeding season based on season, gross examination of ovarian structures, and plasma progesterone concentrations were collected post-mortem. In situ hybridization revealed melatonin receptor (MT1r) mRNA abundantly expressed in glandular cells of the PT in both breeding and non-breeding season mares. Immunofluorescent analysis revealed a higher abundance of TSH-ir cells (p = .0043) in PT obtained during the breeding season compared to the non-breeding season. In cycling mares, MT1r mRNA co-localized with TSH-producing cells in the PT, suggesting a role for TSH as a modulator of seasonal reproduction in the mare. These findings support a role for melatonin and TSH in modulating seasonal reproduction in the mare, further evidenced by the increased TSH immunosignal observed during the breeding season. Altogether, this study endorses the PT as the key site for integrating multiple cues to regulate seasonal reproduction in the horse, as this study marks the first investigation of the relationship between melatonin and PT-specific TSH cells and release in an equine model.
Controversies in NEN: An ENETS position statement on the treatment of patients with Grade 3 well-differentiated neuroendocrine tumours of the gastro-enteropancreatic tract.
McNamara MG, Sorbye H, Begum N … +9 more , Christ E, Fazio N, Fernandez-Cuesta L, Garcia-Carbonero R, Kaltsas G, Kasajima A, Salazar R, Speel EJM, Kjaer A
J Neuroendocrinol · 2025 Dec · PMID 40781987 · Full text
Grade 3 neuroendocrine tumours (NET G3) represent approximately 20% of high-grade neuroendocrine neoplasms, and the recent identification of this entity has given rise to many unanswered questions relating to clinical ma...
Grade 3 neuroendocrine tumours (NET G3) represent approximately 20% of high-grade neuroendocrine neoplasms, and the recent identification of this entity has given rise to many unanswered questions relating to clinical management. The prognosis for these patients is worse than for those with Grade 1-2 well-differentiated NET, but better than for those with Grade 3 poorly differentiated neuroendocrine carcinoma. This consensus statement aims to address some uncertainties and explore unmet needs in the management of patients with NET G3. Firstly, the role of surgery in localised disease will be discussed as well as the dilemma in relation to the use of neo-adjuvant and/or adjuvant treatment in this setting. Treatment of oligometastatic digestive NET G3 will also be examined, including the positioning of surgery and ablative therapy. In the advanced setting, traditionally, chemotherapy in the form of temozolomide/capecitabine or 5-fluorouracil-based therapies, rather than platinum/etoposide, is considered a first-line treatment option, with second-line therapy dependent on what was used first-line. More recently, following the results of the NETTER-2 trial, Peptide Receptor Radionuclide Therapy with Lu-DOTATATE may be an option for selected patients with somatostatin receptor positive NET G3. There is limited data on the use of immunotherapy and targeted therapy in this disease group to date, and some available evidence will be presented. The role for re-biopsy to guide treatment decision-making in patients with digestive NET G3 and whether NET G3 outside of the digestive tract should be treated similarly will also be scrutinised. Prospective studies with translational end-points are required to enable a better understanding of this diagnosis and to facilitate more optimal treatment discoveries.
Impact on symptoms and survival of bone metastases in patients with small-intestinal neuroendocrine tumours.
Wedin M, Janson ET, Wallin G … +2 more , Sundin A, Daskalakis K
J Neuroendocrinol · 2025 Oct · PMID 40778558 · Full text
We aimed to assess the symptoms and impact on overall survival (OS) from bone metastases (BM) diagnosed on Gallium-68-labelled DOTA tyrosine octreotide positron emission tomography with computed tomography (Ga-DOTATOC-PE...
We aimed to assess the symptoms and impact on overall survival (OS) from bone metastases (BM) diagnosed on Gallium-68-labelled DOTA tyrosine octreotide positron emission tomography with computed tomography (Ga-DOTATOC-PET/CT) in patients with well-differentiated small intestinal neuroendocrine tumours (Si-NETs). Patients with well-differentiated Si-NETs, who underwent Ga-DOTATOC-PET/CT between 2010 and 2023 at two tertiary referral centres in Sweden, were included. Their number of BM, ≤5 BM versus >5 BM, symptoms and need for analgesics were recorded. To further assess the impact of BM on OS, we used a control group of age- and sex-matched Si-NET patients with liver metastases (Stage IV disease) but without BM. The prevalence of BM in Si-NET patients was 23% (175/753); among these, complete clinical data were available in 138 patients. Synchronous BM were found in 33% (46/138). Sixty-one patients (44%) showed >5 BM at the time of BM detection. Fractures were diagnosed in 4% (n = 6) and 14% (n = 20) needed analgesics for BM-associated pain. In univariable analysis, patients with >5 BM experienced shorter OS from the time of BM detection compared to those with ≤5 BM (18 months vs. 75 months, p < .001). Among patients with Stage IV disease with and without BM, OS was shorter in patients with BM compared to patients with no BM (72 months vs. 288 months, p = .002). In multivariable analysis of patients with BM, higher Ki-67% (hazard ratio [HR] = 1.06, p = .007), older age (HR = 1.07, p < .01), presence of >5 BM (HR = 1.93, p = .021) and synchronous BM (HR = 2.14, p = .016) were identified as independent prognostic factors for shorter OS. In the matched cohort of patients with Stage IV disease with and without BM, presence of BM (HR = 1.94, p = .009), age at diagnosis of Stage IV (HR = 1.08, p < .001) and locoregional surgical resection (HR = 0.47, p = .015) were independent prognostic factors for survival. BM are detected in approximately 25% of Si-NET patients subjected to Ga-DOTATOC-PET/CT. Pain occurs in approximately 14% and fractures in 4%. The presence of BM among Stage IV patients, the extent of bone disease (>5 BM) and synchronous BM are independent prognostic factors for shorter OS.
Mapping O-linked glycosylation in the rat hypothalamus in pregnancy and lactation.
Murrell CL, Barad Z, Wallace RS … +3 more , Erickson JR, Brown CH, Augustine RA
J Neuroendocrinol · 2025 Dec · PMID 40767381 · Full text
Many maternal adaptations occur during pregnancy to support the metabolic demands of the developing fetus and to prepare for the continued metabolic demands of lactation. Among these maternal adaptations are changes in t...
Many maternal adaptations occur during pregnancy to support the metabolic demands of the developing fetus and to prepare for the continued metabolic demands of lactation. Among these maternal adaptations are changes in the hypothalamic areas that regulate energy homeostasis: the paraventricular nucleus (PVN), ventromedial hypothalamic nucleus (VMH) and arcuate nucleus (ARC). The adaptive changes in the PVN, VMH, and ARC are believed to be driven by reduced responsiveness to the satiety hormone, leptin, during pregnancy. However, increased maternal metabolism is supported by elevated circulating glucose levels in pregnancy, and glucose itself can alter cell function by O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of proteins (O-GlcNAcylation). Therefore, we hypothesized that O-GlcNAcylation would be increased within the hypothalamic brain areas that are involved in the maternal adaptations to the increased metabolic demands of pregnancy: the ARC, VMH, and PVN. We completed immunohistochemistry and western blotting for O-GlcNAc in the ARC, VMH, and PVN from non-pregnant, late-pregnant, and lactating rats. Unexpectedly, we found that the number of O-GlcNAc-expressing cells and the levels of O-GlcNAc protein expression were similar within each area in non-pregnant, late-pregnant, and lactating rats. However, western blot analysis showed that the specific proteins that were O-GlcNAcylated appeared to be different between the reproductive states within each area. Further work will be required to identify the specific proteins that are differentially O-GlcNAcylated in each of the areas during pregnancy and lactation to determine whether this might contribute to the maternal adaptations required to cope with the metabolic demands of pregnancy and lactation.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe