Neuroendocrinology最新文献

{"title":"The role of PD-L1 expression in pituitary tumours: lessons from the current literature.","authors":"Mariana Lopes-Pinto, Ema Lacerda-Nobre, Ana Luísa Silva, Francisco Tortosa, Pedro Marques","doi":"10.1159/000539345","DOIUrl":"https://doi.org/10.1159/000539345","url":null,"abstract":"BACKGROUND\u0000Programmed cell death-1 (PD-1) and PD ligand-1 (PD-L1) expression predicts the biological behaviour, aggres-siveness and response to immune checkpoint inhibitors in different cancers. We reviewed the published data on PD-L1 ex-pression in pituitary tumours, from the perspective of its biological role and prognostic usefulness.\u0000\u0000\u0000SUMMARY\u0000A literature review focused on PD-L1 expression in pituitary tumours was performed. Six immunohistochemistry-based studies which assessed PD-L1 positivity in pituitary tumours were included, encompassing 704 patients. The cohort consisted of 384 (54.5%) non-functioning tumours and 320 (43.5%) functioning pituitary tumours. PD-L1 expression was posi-tive in 248 cases (35.2%). PD-L1 positivity rate was higher in functioning than in non-functioning tumours (46.3% vs 26.0%; p<0.001), but also higher in growth hormone-secreting tumours (56.7%) and prolactinomas (53.6%) than in thyrotroph (33.3%) or corticotroph tumours (20.6%). While proliferative pituitary tumours showed higher rate of PD-L1 positivity than non-proliferative tumours (p<0.001), no association with invasion or recurrence was found.\u0000\u0000\u0000KEY MESSAGES\u0000PD-L1 is expressed in a substantial number of pituitary tumours, predominantly in the functioning ones. PD-L1 positivity rates were significantly higher in proliferative pituitary tumours in comparison to non-proliferative tumours, but no differences were found concerning invasive or recurrent pituitary tumours. More studies following homogeneous and standardised methodologies are needed to fully elucidate the role and usefulness of PD-L1 expression in pituitary tumours.","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140968632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell signaling in the circadian pacemaker: new insights from in vivo imaging.","authors":"X. Bonnefont","doi":"10.1159/000539344","DOIUrl":"https://doi.org/10.1159/000539344","url":null,"abstract":"BACKGROUND\u0000\"One for all, and all for one\", the famous rallying cry of The Three Musketeers, in Alexandre Dumas's popular novel, certainly applies to the 20,000 cells composing the suprachiasmatic nuclei (SCN). These cells work together to form the central clock that coordinates body rhythms in tune with the day-night cycle. Like virtually every body cell, individual SCN cells exhibit autonomous circadian oscillations, but this rhythmicity only reaches a high level of precision and robustness when the cells are coupled with their neighbors. Therefore, understanding the functional network organization of SCN cells beyond their core rhythmicity is an important issue in circadian biology.\u0000\u0000\u0000SUMMARY\u0000The present review summarizes the main results from our recent study demonstrating the feasibility of recording SCN cells in freely moving mice and the significance of variations in intracellular calcium over several timescales.\u0000\u0000\u0000KEY MESSAGE\u0000We discuss how in vivo imaging at the cell level will be pivotal to interrogate the mammalian master clock, in an integrated context that preserves the SCN network organization, with intact inputs and outputs.","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140969444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collagen XIII is the Key Molecule of Neurovascular Junctions in the Neuroendocrine System.","authors":"T. Nakakura, Kotaro Horiguchi, Takeshi Suzuki","doi":"10.1159/000538976","DOIUrl":"https://doi.org/10.1159/000538976","url":null,"abstract":"INTRODUCTION\u0000Axons of magnocellular neurosecretory cells project from the hypothalamus to the posterior lobe (PL) of pituitary. In the PL, a wide perivascular space exists between the outer basement membrane (BM), where nerve axons terminate, and the inner BM lining the fenestrated capillaries. Hypothalamic axon terminals and outer BMs in the PL form neurovascular junctions. We previously had found that collagen XIII is strongly localized in the outer BMs. In this study, we investigated the role of collagen XIII in the PL of rat pituitaries.\u0000\u0000\u0000METHODS\u0000We first studied the expression of Col13a1, the gene encoding the α1 chains of collagen XIII, in rat pituitaries via qPCR and in situ hybridization. We observed the distribution of COL13A1 in rat pituitary using immunohistochemistry and immunoelectron microscopy. We examined the expression of Col13a1 and the distribution of COL13A1 during the development of pituitary. In addition, we examined the effects of water deprivation and arginine vasopressin (AVP) signaling on the expression of Col13a1 in the PL.\u0000\u0000\u0000RESULTS\u0000Col13a1 was expressed in NG2-positive pericytes, and COL13A1 signals were localized in the outer BM of the PL. The expression of Col13a1 was increased by water deprivation and was regulated via the AVP/AVPR1A/Gαq/11 cascade in pericytes of the PL.\u0000\u0000\u0000CONCLUSION\u0000These results suggest that pericytes surrounding fenestrated capillaries in the PL secrete COL13A1 and are involved in the construction of neurovascular junctions. COL13A1 is localized in the outer BM surrounding capillaries in the PL and may be involved in the connection between capillaries and axon terminals.","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140681293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic Profiling of Lactotroph Pituitary Neuroendocrine Tumors via RNA Sequencing and Ingenuity Pathway Analysis.","authors":"Yujiro Hattori, S. Tahara, Hitoshi Ozawa, Akio Morita, H. Ishii","doi":"10.1159/000539017","DOIUrl":"https://doi.org/10.1159/000539017","url":null,"abstract":"INTRODUCTION\u0000Lactotroph pituitary neuroendocrine tumors (PitNETs) are common pituitary tumors, but their underlying molecular mechanisms remain unclear. This study aimed to investigate the transcriptomic landscape of lactotroph PitNETs and identify potential molecular mechanisms and therapeutic targets through RNA sequencing and ingenuity pathway analysis (IPA).\u0000\u0000\u0000METHODS\u0000Lactotroph PitNET tissues from five surgical cases without dopamine agonist treatment underwent RNA sequencing. Normal pituitary tissues from three patients served as controls. Differentially expressed genes (DEGs) were identified, and the functional pathways and gene networks were explored by IPA.\u0000\u0000\u0000RESULTS\u0000Transcriptome analysis revealed that lactotroph PitNETs had gene expression patterns that were distinct from normal pituitary tissues. We identified 1,172 upregulated DEGs, including nine long intergenic noncoding RNAs (lincRNAs) belonging to the top 30 DEGs. IPA of the upregulated DEGs showed that the estrogen receptor signaling, oxidative phosphorylation signaling, and EIF signaling were activated. In gene network analysis, key upstream regulators, such as EGR1, PRKACA, PITX2, CREB1, and JUND, may play critical roles in lactotroph PitNETs.\u0000\u0000\u0000CONCLUSION\u0000This study provides a comprehensive transcriptomic profile of lactotroph PitNETs and highlights the potential involvement of lincRNAs and specific signaling pathways in tumor pathogenesis. The identified upstream regulators may be potential therapeutic targets for future investigations.","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140681461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypothalamic GABAergic neurons expressing Cellular Retinoic Acid Binding Protein 1 (CRABP1) are sensitive to metabolic status and liraglutide in male mice.","authors":"Olivier Lavoie, Audrey Turmel, Paige Mattoon, W. Desrosiers, Julie Plamondon, Natalie Jane Michael, Alexandre Caron","doi":"10.1159/000538716","DOIUrl":"https://doi.org/10.1159/000538716","url":null,"abstract":"INTRODUCTION\u0000Owing to their privileged anatomical location, neurons of the arcuate nucleus of the hypothalamus (ARC) play critical roles in sensing and responding to metabolic signals such as leptin and glucagon-like peptide 1 (GLP-1). In addition to the well-known proopiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurons, subpopulations of GABAergic neurons are emerging as key regulators of energy balance. However, the precise identity of these metabolic neurons is still elusive. Here, we identified and characterized the molecular signature of a novel population of GABAergic neurons of the ARC expressing Cellular retinoic acid binding protein 1 (Crabp1).\u0000\u0000\u0000METHODS\u0000Using a combination of immunohistochemistry and in situ hybridization techniques, we investigated the expression of Crabp1 across the mouse brain and characterized the molecular identity of Crabp1ARC neurons. We also determined whether Crabp1ARC neurons are sensitive to fasting, leptin and GLP1R agonism by assessing cFOS immunoreactivity as a marker of neuronal activity.\u0000\u0000\u0000RESULTS\u0000Crabp1ARC neurons represent a novel GABAergic neuronal population robustly enriched in the ARC and distinct from the prototypical melanocortin neurons. Crabp1ARC neurons overlap with three subpopulations of yet uncharacterized ARC neurons expressing Htr3b, Tbx19 and Tmem215, respectively. Notably, Crabp1ARC neurons express receptors for metabolic hormones and their activity is modulated by the nutritional state and GLP1R agonism.\u0000\u0000\u0000CONCLUSION\u0000Crabp1ARC neurons represent a novel heterogenous population of GABAergic neurons sensitive to metabolic status.","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140691541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromaffin Cells in the Mammalian Adrenomedullary Tissue: Ultrastructural Aspects of Stimulus-Secretion Coupling - A Tribute to Odile Grynszpan-Winograd (1938-2023).","authors":"Nathalie C. Guérineau, Dominique Aunis","doi":"10.1159/000538302","DOIUrl":"https://doi.org/10.1159/000538302","url":null,"abstract":"","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140696695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 26RFa (QRFP)/GPR103 neuropeptidergic system: A key regulator of energy and glucose metabolism.","authors":"Mélodie Devère, Saloua Takhlidjt, Gaëtan Prévost, Nicolas Chartrel, Jérôme Leprince, M. Picot","doi":"10.1159/000538629","DOIUrl":"https://doi.org/10.1159/000538629","url":null,"abstract":"BACKGROUND\u0000Obesity and type 2 diabetes are strongly associated pathologies, currently considered as a worldwide epidemic problem. Understanding the mechanisms that drive the development of these diseases would enable to develop new therapeutic strategies for their prevention and treatment. Particularly, the role of the brain in the energy and glucose homeostasis has been studied for two decades. In specific, the hypothalamus contains well-identified neural networks regulating appetite and potentially also glucose homeostasis. A new concept has thus emerged, suggesting that obesity and diabetes could be due to a dysfunction of the same, still poorly understood, neural networks.\u0000\u0000\u0000SUMMARY\u0000The neuropeptide 26RFa (also termed QRFP) belongs to the family of RFamide regulatory peptides and has been identified as the endogenous ligand of the human G protein-coupled receptor GPR103 (QRFPR). The primary structure of 26RFa is strongly conserved during vertebrate evolution, suggesting its crucial roles in the control of vital functions. Indeed, the 26RFa/GPR103 peptidergic system is reported to be involved in the control of various neuroendocrine functions, notably the control of energy metabolism in which it plays an important role, both centrally and peripherally, since 26RFa regulates feeding behavior, thermogenesis and lipogenesis. Moreover, 26RFa is reported to control glucose homeostasis both peripherally, where it acts as an incretin, and centrally, where the 26RFa/GPR103 system relays insulin signaling in the brain to control glucose metabolism.\u0000\u0000\u0000KEY MESSAGES\u0000This review gives a comprehensive overview of the role of the 26RFa/GPR103 system as a key player in the control of energy and glucose metabolism. In pathophysiological context, this neuropeptidergic system represents a prime therapeutic target whose mechanisms are highly relevant to decipher.","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140716635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic co-administration of low dose oxytocin and glucagon like peptide-1 additively decreases food intake and body weight.","authors":"Yuko Maejima, Shoko Yokota, S. Hidema, Katsuhiko Nishimori, Heidi de Wet, Kenju Shimomura","doi":"10.1159/000538792","DOIUrl":"https://doi.org/10.1159/000538792","url":null,"abstract":"INTRODUCTION\u0000GLP-1 receptor agonists are the number one drug prescribed for the treatment of obesity and type 2 diabetes. These drugs are not, however, without side-effects and in an effort to maximize therapeutic effect while minimizing adverse effects, gut hormone co-agonists received considerable attention as new drug targets in the fight against obesity. Numerous previous reports identified the neuropeptide oxytocin (OXT) as a promising anti-obesity drug. The aim of this study is to evaluate OXT as a possible co-agonist for GLP-1 and examine the effects of its co-administration on food intake (FI) and body weight (BW) in mice.\u0000\u0000\u0000METHODS\u0000FI and c-Fos levels were measured in the feeding-centers of the brain in response to an intraperitoneal injection of saline, OXT, GLP-1 or OXT/GLP-1. The action potential frequency and cytosolic Ca2+ ([Ca2+]i) in response to OXT, GLP-1 or OXT/GLP-1were measured in ex-vivo PVN neuronal cultures. Finally, FI and BW changes were compared in diet induced obese mice treated with saline, OXT, GLP-1 or OXT/GLP-1 for 13 days.\u0000\u0000\u0000RESULTS\u0000Single injection of OXT/GLP-1 additively decreased FI, and increased c-Fos expression specifically in the paraventricular (PVN) and supraoptic nucleus (SON). 70% of GLP-1 receptor positive neurons in the PVN also expressed OXT receptors, and OXT/GLP-1 co-administration dramatically increased firing and [Ca2+]i in the PVN OXT neurons. The chronic OXT/GLP-1 co-administration decreased BW without changing FI.\u0000\u0000\u0000CONCLUSION\u0000Chronic OXT/GLP-1 co-administration decreases BW, possibly via the activation of PVN OXT neurons. OXT might be a promising candidate as an incretin co-agonist in obesity treatment.","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140719804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/000538574","DOIUrl":"https://doi.org/10.1159/000538574","url":null,"abstract":"","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140732142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to Progestin 17-OHPC Induces Gastrointestinal Dysfunction through Claudin 1 Suppression in Female Mice with Increased Anxiety-Like Behaviors.","authors":"Liqin Zeng, Xiaozhuang Zhang, Qingjun Shen, Li He, Xiaohan Liu, Xiangyue Zeng, Qiaozhu Wu, Irene Ma, Shuangyun Zheng, Liqin Cheng, Ling Li, Paul Yao","doi":"10.1159/000538692","DOIUrl":"https://doi.org/10.1159/000538692","url":null,"abstract":"INTRODUCTION\u0000Progestin, commonly used in oral contraception and preventing preterm birth, elicits various off-target side effects on brain and gastrointestinal (GI) functions, yet the precise mechanisms remain elusive. This study aims to probe progestin's impact on GI function and anxiety-like behaviors in female mice.\u0000\u0000\u0000METHODS\u0000Colon stem cells were utilized to explore the mechanism underlying progestin 17-hydroxyprogesterone caproate (17-OHPC)-mediated suppression of claudin-1 (CLDN1), crucial for epithelial integrity. Chromatin immunoprecipitation and luciferase assays identified potential progestin-response elements on the CLDN1 promoter, with subsequent assessment of oxidative stress and pro-inflammatory cytokine release. Manipulation of vitamin D receptor (VDR) or estrogen receptor β (ERβ) expression elucidated their roles in 17-OHPC-mediated effects. Intestine-specific VDR deficient mice were generated to evaluate 17-OHPC's impact on GI dysfunction and anxiety-like behaviors in female mice. Additionally, gene expression was analyzed in various brain regions, including the amygdala, hypothalamus, and hippocampus.\u0000\u0000\u0000RESULTS\u0000Exposure to 17-OHPC suppressed CLDN1 expression via epigenetic modifications and VDR dissociation from the CLDN1 promoter. Furthermore, 17-OHPC intensified oxidative stress and proinflammatory cytokine release. VDR knockdown partly mimicked, while overexpression of either VDR or ERβ partly restored 17-OHPC-mediated effects. Intestinal VDR deficiency partly mirrored 17-OHPC-induced GI dysfunction, with minimal impact on 17-OHPC-mediated anxiety-like behaviors.\u0000\u0000\u0000CONCLUSIONS\u000017-OHPC suppresses CLDN1 expression through VDR, contributing to GI dysfunction in female mice, distinct from 17-OHPC-induced anxiety-like behaviors. This study reveals a new mechanism and potential negative impact of progestin exposure on the gastrointestinal tract, alongside inducing anxiety-like behaviors in female mice.","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140735127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}