Journal of Neuroendocrinology最新文献

{"title":"PTPRJ is a negative regulator of insulin signaling in neuronal cells, impacting protein biosynthesis, and neurite outgrowth","authors":"Jannis Ulke,&nbsp;Simran Chopra,&nbsp;Otsuware Linda-Josephine Kadiri,&nbsp;Peter Geserick,&nbsp;Vanessa Stein,&nbsp;Sahar Cheshmeh,&nbsp;André Kleinridders,&nbsp;Kai Kappert","doi":"10.1111/jne.13446","DOIUrl":"10.1111/jne.13446","url":null,"abstract":"<p>Central insulin resistance has been linked to the development of neurodegenerative diseases and mood disorders. Various proteins belonging to the enzyme family of protein tyrosine phosphatases (PTPs) act as inhibitors of insulin signaling. Protein tyrosine phosphatase receptor type J (PTPRJ) has been identified as a negative regulator in insulin signaling in the periphery. However, the impact of PTPRJ on insulin signaling and its functional role in neuronal cells is largely unknown. Therefore, we generated a <i>Ptprj</i> knockout (KO) cell model in the murine neuroblast cell line Neuro2a by CRISPR-Cas9 gene editing. <i>Ptprj</i> KO cells displayed enhanced insulin signaling, as shown by increased phosphorylation of the insulin receptor (INSR), IRS-1, AKT, and ERK1/2. Further, proximity ligation assays (PLA) revealed both direct interaction of PTPRJ with the INSR and recruitment of this phosphatase to the receptor upon insulin stimulation. By RNA sequencing gene expression analysis, we identified multiple gene clusters responsible for glucose uptake and metabolism, and genes involved in the synthesis of various lipids being mainly upregulated under PTPRJ deficiency. Furthermore, multiple Ca²⁺ transporters were differentially expressed along with decreased protein biosynthesis. This was accompanied by an increase in endoplasmic reticulum (ER) stress markers. On a functional level, PTPRJ deficiency compromised cell differentiation and neurite outgrowth, suggesting a role in nervous system development. Taken together, PTPRJ emerges as a negative regulator of central insulin signaling, impacting neuronal metabolism and neurite outgrowth.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 12","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208508","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":"Functional diversity along the anteroposterior axis of the ventromedial hypothalamus","authors":"Nicolas Gutierrez‐Castellanos, Inês C. Dias, Basma F. A. Husain, Susana Lima","doi":"10.1111/jne.13447","DOIUrl":"https://doi.org/10.1111/jne.13447","url":null,"abstract":"Innate behaviors ensure animal survival and reproductive success. Defending their territory, escaping from predators or mating with a sexual partner, are fundamental behaviors determining the ecological fitness of individuals. Remarkably, all these behaviors share a common neural substrate, as they are under the control of the ventromedial hypothalamus (VMH). Decades of research have contributed to understanding the exquisite diversity of functional ensembles underlying the wide array of functions that the VMH carries out. These functional ensembles are usually distributed throughout the dorsoventral and mediolateral axes of this nucleus. However, increasing evidence is bringing to attention the functional diversity of the VMH across its anteroposterior axis. In this review, we will overview our current understanding of how different ensembles within the VMH control a wide array of animal behaviors, emphasizing the newly discovered roles for its anterior subdivision in the context of conspecific self‐defense.","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"254 1","pages":"e13447"},"PeriodicalIF":3.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208509","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":"PRRT in high-grade digestive neuroendocrine neoplasms (NET G3 and NEC)","authors":"Halfdan Sorbye,&nbsp;Grace Kong,&nbsp;Simona Grozinsky-Glasberg,&nbsp;Jonathan Strosberg","doi":"10.1111/jne.13443","DOIUrl":"10.1111/jne.13443","url":null,"abstract":"<p>Peptide receptor radionuclide therapy (PRRT) has been primarily studied in low and intermediate-grade digestive neuroendocrine tumors (NET G1-G2). The documentation of a similar benefit for high-grade digestive neuroendocrine neoplasms (NEN) has been limited. This review evaluates the use of PRRT for high-grade digestive NEN (well-differentiated NET G3 and poorly differentiated neuroendocrine carcinomas [NEC]). We identified one phase III trial and seven retrospective studies reporting specifically on PRRT outcome of &gt;10 digestive high-grade NEN patients. The retrospective single-arm studies indicate a benefit for PRRT in NET G3. The randomized phase III NETTER-2 trial demonstrates major PFS superiority of PRRT versus somatostatin analog therapy as the first-line treatment for the NET G3 subgroup. PRRT can now be considered a potential first-line treatment for somatostatin receptor-positive NET G3 patients, but whether it should be the first-line standard of care for all NET G3 patients is still not clarified. For NEC, scarce data are available, and pathologic distinction between NEC and NET G3 can be difficult when Ki-67 is below 55%. PRRT could be considered as a treatment for refractory NEC in very selected cases when there is a high uptake on somatostatin receptor imaging, Ki-67 is below 55%, and there is no rapid tumor progression.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"37 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145811","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":"Gastric neuroendocrine tumors: 20-Year experience in a reference center","authors":"Davide Ravizza,&nbsp;Mariangela Giunta,&nbsp;Isabella Sala,&nbsp;Vincenzo Bagnardi,&nbsp;Darina Tamayo,&nbsp;Giuseppe de Roberto,&nbsp;Cristina Trovato,&nbsp;Ivana Bravi,&nbsp;Pietro Soru,&nbsp;Margherita Maregatti,&nbsp;Eleonora Pisa,&nbsp;Emilio Bertani,&nbsp;Guido Bonomo,&nbsp;Francesca Spada,&nbsp;Fazio Nicola","doi":"10.1111/jne.13440","DOIUrl":"10.1111/jne.13440","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Few studies have been published on the long-term outcomes of patients with gastric neuroendocrine tumors (gNETs). We analyzed their management over a two-decade period, focusing on endoscopic and clinical outcomes. Clinical, laboratory, endoscopic, surgical, and histopathological data from Types 1 and 3 gNETs histologically diagnosed between March 2000 and December 2021 at the European Institute of Oncology (IEO, Milan) were retrospectively collected. Sixty-nine patients were included (60 Type 1, 9 Type 3): 53 (77%) were treated endoscopically, 6 (9%) surgically, and 10 (14%) did not receive any treatment. Overall, 293 lesions were removed endoscopically: 74% by forceps, 20% by endoscopic mucosal resection (EMR), and 5% by endoscopic submucosal dissection (ESD). No differences were observed between EMR and ESD in terms of complete resection rate (<i>p</i> value = .50) and complications rate (<i>p</i> value = .084). The median follow-up period was 5.8 years (range: 0.3–20.5), during which no gNET-related deaths were observed. Metachronous gNETs developed in 60% of patients with Type 1 gNET. Six patients with lymph node metastases (LNM) were younger (<i>p</i> value = .006) and had larger lesions (<i>p</i> value &lt;.001) than patients without LNM. Most Type 1 gNETs were successfully excised using forceps, with EMR and ESD being equally effective. The presence of incomplete resection was not associated with a worse prognosis, which remains excellent in this highly recurrent disease. Younger age and a size ≥10 mm were associated with an increased risk of LNM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Clinical Trial Registration</h3>\u0000 \u0000 <p>Project code UID 2854.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 12","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080550","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":"Hypothalamic obesity: Epidemiology in rare sellar/suprasellar tumors—A German claims database analysis","authors":"Julian Witte,&nbsp;Bastian Surmann,&nbsp;Manuel Batram,&nbsp;Markus Weinert,&nbsp;Mathias Flume,&nbsp;Nicolas Touchot,&nbsp;Julia Beckhaus,&nbsp;Carsten Friedrich,&nbsp;Hermann L. Müller","doi":"10.1111/jne.13439","DOIUrl":"10.1111/jne.13439","url":null,"abstract":"<p>Hypothalamic obesity (HO) is defined as abnormal weight gain resulting in severe persistent obesity due to physical, tumor- and/or treatment-related damage to the hypothalamus. HO epidemiology is poorly understood. We developed a database algorithm supporting the standardized identification of tumor/treatment-related HO (TTR-HO) patients. The algorithm is used to estimate incidence rates of TTR-HO patients in the German healthcare context from a representative claims database (<i>n</i> = 5.42 million) covering 2010–2020. Patients were identified based on surgery/radiotherapy procedures and HO-associated tumor diagnoses (<i>n</i> = 3976). HO was defined by incident obesity and validated based on incident diabetes insipidus diagnoses and desmopressin prescription within a 12-month period after surgery/radiotherapy. Uncertainty due to algorithm definitions is explored in sensitivity analyses. Estimated annual incidence of TTR-HO in Germany is between 0.7 and 1.7 cases per 1,000,000 persons (2019 prevalence: <i>n</i> = 1262 patients). With observed cases in all age groups, two HO-incidence peaks are identified: children/young adults aged 10–24 years and adults aged 40–44 years. Most frequent HO-validated tumor diagnoses are benign sellar/suprasellar tumors (6.1/1,000,000 persons over 9 years), including tumors of the craniopharyngeal duct (1.3/1,000,000), neoplasms of the pituitary gland (4.1/1,000,000), and nonspecific brain tumors of endocrine glands (2.4/1,000,000). This is the first real-world database analysis of TTR-HO epidemiology, refining current estimates of HO epidemiology and early patient identification. A more comprehensive characterization of patients with HO as well as a better understanding of clinical implications will be crucial in developing optimal treatment strategies to improve patient outcomes.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 12","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080551","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":"Estrogenic regulation of hippocampal inhibitory system across lifespan.","authors":"Pablo Méndez, Rut de la Vega-Ruiz, Alberto Montes-Mellado","doi":"10.1111/jne.13441","DOIUrl":"https://doi.org/10.1111/jne.13441","url":null,"abstract":"<p><p>Estrogens produced in peripheral tissues and locally in the brain are potent neuromodulators. The function of the hippocampus, a brain region essential for episodic memory and spatial navigation, relies on the activity of ensembles of excitatory neurons whose activity is temporally and spatially coordinated by a wide diversity of inhibitory neurons (INs) types. Over the last years, we have accumulated evidence that indicates that estrogens regulate the function of hippocampal INs through different mechanisms, including transcriptional regulation and rapid nongenomic signaling. Here, we argue that the well-documented influence of estrogens on episodic memory may be related to the actions of local and peripheral estrogens on the heterogenous populations of hippocampal INs. We discuss how physiological changes in peripheral sex hormone levels throughout lifespan may interact with local brain sources to regulate IN function at different stages of life, from early hippocampal development to the aging brain. We conclude that considering INs as mediators of sex hormone actions in the hippocampus across the healthy life span will benefit our understanding of sex-biased neurodevelopmental disorders and physiological aging.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13441"},"PeriodicalIF":3.3,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982561","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":"Understanding negative feedback: Changes in high-molecular-weight adrenocorticotropic hormone in adrenocorticotropic hormone-independent Cushing's syndrome","authors":"Yuto Ichinose,&nbsp;Mei Nakatsuji,&nbsp;Hironori Bando,&nbsp;Masaaki Yamamoto,&nbsp;Maki Kanzawa,&nbsp;Kei Yoshino,&nbsp;Hidenori Fukuoka,&nbsp;Wataru Ogawa","doi":"10.1111/jne.13438","DOIUrl":"10.1111/jne.13438","url":null,"abstract":"<p>Cushing's syndrome is characterized by chronic glucocorticoid oversecretion and diverse clinical manifestations. Distinguishing between adrenocorticotropic hormone (ACTH)-independent and ACTH-dependent forms is crucial for determining treatment options. Plasma ACTH levels aid in the differential diagnosis, with undetectable or low levels suggesting ACTH-independent hypercortisolemia. ACTH is derived from pro-opiomelanocortin, and its processing involves prohormone convertase 1/3. High-molecular-weight ACTH is generally found in ACTH-producing pituitary tumors and ectopic ACTH syndrome. The mechanism of negative feedback and the process of high-molecular-weight ACTH alternation during ACTH-independent Cushing's syndrome remain unclear. A 40-year-old woman with hypertension and multiple fractures developed symptoms suggestive of Cushing's syndrome. Computed tomography revealed a left adrenocortical tumor along with atrophy of the right adrenal gland. ACTH levels were undetectable at the previous clinic, indicating ACTH-independent Cushing's syndrome. However, subsequent measurements at our hospital revealed non-suppressed ACTH (18.1 pg/mL), prompting further investigation. Gel exclusion chromatography confirmed the presence of high-molecular-weight ACTH. Metyrapone treatment decreased the cortisol levels. In this situation, in which ACTH levels should be elevated, a decrease in high-molecular-weight ACTH levels was observed. Histological findings revealed cortisol-producing adenoma without ACTH expression. This case highlights the importance of assay differences in evaluating ACTH concentrations and introduces a novel finding of circulating high-molecular-weight ACTH. The observed decline in high-molecular-weight ACTH levels suggests a potential time lag in the negative feedback within the hypothalamic–pituitary–adrenal axis exhibited by glucocorticoids. This temporal aspect of the regulation of ACTH-related molecules warrants further exploration to enhance our understanding of the hypothalamic–pituitary–adrenal axis feedback mechanism.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971313","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":"Association of glycosylated hemoglobin concentrations with structural and functional brain changes in the normoglycemic population: A systematic review","authors":"Yunus Soleymani,&nbsp;Seyed Amir Hossein Batouli,&nbsp;Amin Akbari Ahangar,&nbsp;Ata Pourabbasi","doi":"10.1111/jne.13437","DOIUrl":"10.1111/jne.13437","url":null,"abstract":"<p>Optimal glucose control is crucial for maintaining brain health and preventing metabolic and cognitive disorders in the general population. Glycosylated hemoglobin (HbA1c) serves as a key marker for assessing glucose intolerance and its impact on brain structure and function in healthy individuals. However, existing literature presents conflicting findings, necessitating a systematic review to consolidate current knowledge in this domain. This systematic review examines 26 English-language studies involving participants aged 15 years and above, investigating the relationship between HbA1c levels and brain health. Studies focusing on normal/general populations and utilizing magnetic resonance imaging (MRI) as the imaging modality were included. Exclusion criteria encompassed review articles, abstracts, letters, animal studies, and research involving neuropsychiatric or metabolic diseases. Data were gathered from PubMed, Scopus, and Web of Science databases up to November 2023. Analysis reveals significant associations between HbA1c levels and various brain metrics, including volume, cortical thickness, fractional anisotropy, mean diffusivity, activity, and connectivity. However, findings exhibit inconsistency, likely attributed to disparities in sample characteristics and study sizes. Notably, hippocampal volume, white matter hyperintensity, and ventral attention network connectivity emerge as frequently affected structures and functions, mirroring trends observed in diabetic populations. Despite inconclusive evidence, glucose intolerance appears to exert considerable influence on select brain structures and functions in individuals without diagnosed metabolic disorders. Understanding these associations is critical for mitigating the risk of cognitive decline and dementia in healthy populations. Future investigations should aim to elucidate the intricate relationship between HbA1c concentrations and brain health parameters in normoglycemic individuals.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889496","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":"Intraperitoneal administration of α-melanocyte stimulating hormone (α-MSH) suppresses food intake and induces anxiety-like behavior via the brain MC4 receptor-signaling pathway in goldfish","authors":"Keisuke Watanabe,&nbsp;Norifumi Konno,&nbsp;Tomoya Nakamachi,&nbsp;Kouhei Matsuda","doi":"10.1111/jne.13435","DOIUrl":"10.1111/jne.13435","url":null,"abstract":"<p>α-Melanocyte stimulating hormone (α-MSH) is a peptide hormone released from the intermediate lobe of the pituitary which regulates body pigmentation. In addition to the pituitary, α-MSH is also produced in the midbrain, and exerts both anorexigenic and an anxiogenic actions. Acyl ghrelin and cholecystokinin are peripheral hormones derived from the digestive tract which affect the brain to control food intake and feeding behavior in vertebrates. In the present study, hypothesizing that plasma α-MSH may also stimulate the brain and exert central effects, we examined whether peripherally administered α-MSH affects food intake and psychomotor activity using a goldfish model. Intraperitoneal (IP) administration of α-MSH at 100 pmol g⁻¹ body weight (BW) reduced food consumption and enhanced thigmotaxis. These α-MSH-induced actions were blocked by intracerebroventricular administration of HS024, an antagonist of the melanocortin 4 receptor (MC4R), at 50 pmol g⁻¹ BW, whereas these actions were not attenuated by pretreatment with an IP-injected excess amount of capsaicin, a neurotoxin that destroys primary sensory (vagal and splanchnic) afferents, at 160 nmol g⁻¹ BW. Transcripts for the MC4R showed higher expression in the diencephalon in other regions of the brain. These results suggest that, in goldfish, IP administered α-MSH is taken up by the brain, and also acts as anorexigenic and anxiogenic factor via the MC4R signaling pathway.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875139","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":"Announcement: Gregory F. Ball wins the 2024 Donald S. Farner Medal for Excellence in Research in the Field of Avian Endocrinology.","authors":"Jacques Balthazart","doi":"10.1111/jne.13436","DOIUrl":"https://doi.org/10.1111/jne.13436","url":null,"abstract":"","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13436"},"PeriodicalIF":3.3,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792657","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}