Neuroendocrinology最新文献

{"title":"Loss of DAXX/ATRX protein expression results in ischemia resistance and radiation sensitivity in pancreatic neuroendocrine tumor cells and is associated with improved response to trans-arterial radio-embolization.","authors":"Jessica C Puzzuoli, Caleb Solivio, Gavin Yuan, Anthony J Rizzo, Mindy K Graham, Larissa Shenker, Will Vista, Adam Gil, Himanshu Singh, Erica Alexander, Adrian Gonzalez-Aguirre, Jonathan Latzman, E Nadia Petre, Hooman Yarmohammadi, Joseph P Erinjeri, Anne Covey, Eric Chan, James Russell, Lisa Bodei, Nitya Raj, Diane Reidy-Lagunes, Christopher M Heaphy, Etay Ziv","doi":"10.1159/000547041","DOIUrl":"https://doi.org/10.1159/000547041","url":null,"abstract":"<p><strong>Ntroduction: </strong>Metastatic liver pancreatic neuroendocrine tumors (PNETs) can be treated with ischemia-based (trans-arterial embolization [TAE]/trans-arterial chemo-embolization [TACE]) or radiation-based (trans-arterial radioembolization [TARE]). Guidelines for treatment selection are limited. The purpose of this study was to measure the effect of loss of DAXX/ATRX protein expression on ischemia and radiation sensitivity in Bon-1 and QGP-1 cells, and to compare TARE response in PNETs with and without a DAXX/ATRX mutation.</p><p><strong>Methods: </strong>This was a laboratory investigation and retrospective review of an institutional database of TARE-treated PNET patients. Ischemia and radiation sensitivity were tested on Bon-1 and QGP-1 cells and CRISPR-generated DAXX (C16/C45) and ATRX (QAX12/QAX24) knockouts. Post-ischemia and post-radiation cell viability, survival fraction and caspase-3 expression were measured. Local progression free survival (LPFS) was measured from time of TARE to local progression or death and estimated using Cox proportional hazards.</p><p><strong>Results: </strong>Post-ischemia DAXX (C16/C45) and ATRX (QAX12/QAX24) knockouts had increased cell viability compared with Bon-1 wild type cells (p<0.0001, days 3, 5) and QGP-1 wild type cells (p<0.0001, days 3, 5, 7). Post-radiation C16/C45 and QAX12/QAX24 had decreased survival fraction compared with respective wild type (p<0.0001, all cell lines). C16/C45 had decreased apoptotic activity post-ischemia and increased apoptotic activity post-radiation compared with wild type (p<0.0001, all cell lines). Presence of DAXX/ATRX mutation was associated with longer LPFS after TARE (p<0.001). Median LPFS after TARE was 6 months in wild type compared with 22 months in patients with DAXX/ATRX mutation.</p><p><strong>Conclusion: </strong>Loss of DAXX/ATRX protein expression is associated with ischemia resistance and radiation sensitivity in Bon-1 and QGP-1 cells and longer LPFS after TARE in PNET patients.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-20"},"PeriodicalIF":3.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708314","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":"Steroids and one-carbon metabolism: clinical implications in endocrine disorders.","authors":"Nicolas Scheyer, Rosa-Maria Guéant-Rodriguez, Mikaël Agopiantz, Brigitte Leininger-Muller","doi":"10.1159/000547151","DOIUrl":"https://doi.org/10.1159/000547151","url":null,"abstract":"<p><strong>Background: </strong>One-carbon metabolism (OCM) and steroid metabolism are fundamental biochemical pathways that regulate essential cellular processes and physiological functions. OCM is involved in DNA synthesis, methylation, and redox balance, while steroid metabolism governs the production and degradation of steroid hormones, which influence notably growth, reproduction, and stress responses. Despite their distinct roles, emerging evidence suggests a strong interplay between these two pathways.</p><p><strong>Summary: </strong>This review examines the bidirectional relationship between OCM and steroid metabolism, emphasizing their shared intermediates and co-factors. Folate and methionine, key components of OCM, influence steroid biosynthesis, while the methylation status regulated by OCM affects the expression of steroidogenic enzymes. Conversely, steroid hormones modulate OCM by altering the activity of enzymes in folate and methionine cycles. Disruptions in either pathway are linked to diseases such as cancer, cardiovascular disorders, and neurodegenerative conditions. This narrative review examines the clinical and pre-clinical data on the interactions between OCM and sex steroids, in both women and men, adrenal steroids and vitamin D metabolism.</p><p><strong>Key messages: </strong>The interdependence between OCM and steroid metabolism highlights the need to consider both pathways in disease pathogenesis and therapeutic strategies. Their crosstalk plays a crucial role in maintaining cellular homeostasis and responding to metabolic stress. Targeting this metabolic interplay offers new opportunities for treating metabolic disorders, with potential clinical applications in modulating one pathway to influence the other for more integrated disease management.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-38"},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584279","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":"Role of melatonin in intestinal mucosal injury induced by chronic restraint stress in mice.","authors":"Sun Zhongxin, Chai Lulu, Li Dandan, Yang Yao, Yao Wenqian, Li Hui, Shan Chunlan, Wen Xin, Lin Rutao","doi":"10.1159/000547254","DOIUrl":"https://doi.org/10.1159/000547254","url":null,"abstract":"<p><strong>Introduction: </strong>A growing body of evidence demonstrates that gastrointestinal motility disorder (GIMD) and gastric stress ulcers can be induced by chronic stress, whereas melatonin (MT) elicits anti-inflammatory and antioxidant effects. The present study investigated the mechanisms of MT-mediated protection against chronic restraint stress-induced GIMD.</p><p><strong>Methods: </strong>Sixty 8-week-old male ICR mice were divided into four groups: control, restraint stress, restraint stress + MT and MT (positive control). MT (20 mg/kg) or vehicle was administered intraperitoneally 60 minutes before chronic restraint stress (5 hours/day) once daily for 30 days. Biochemical parameters, intestinal mucosal integrity, tissue antioxidant ability and autophagic protein levels were determined.</p><p><strong>Results: </strong>Mice subjected to restraint stress presented elevated CORT and NE levels of 141.41% and 151.24%, respectively, and a decreased plasma MT content of 37.12%. Consistent with the decrease in MT levels, we observed a reduction in antioxidant ability and autophagic proteins and increased apoptotic protein levels in the gut, resulting in injury to the intestinal mucosa, which manifested as reductions in the villus height and the V/C ratio; the number of goblets; the number of mast and PCNA-positive cells; and the expression of tight junction proteins (ZO-1, occludin and claudin-1). In contrast, MT reversed these changes caused by chronic restraint stress and improved intestinal mucosal injury. However, there was no significant difference between the MT (positive control) and control groups.</p><p><strong>Conclusion: </strong>Our results suggest that MT effectively mitigates chronic psychological stress-induced intestinal mucosa injury, providing evidence demonstrating the potential for the use of MT as a therapy for intestinal impairment associated with chronic psychological stress.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-24"},"PeriodicalIF":3.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575923","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":"Impact of hyperoside on the blood-brain barrier in rats with bacterial meningitis through the microRNA-155/BDNF pathway.","authors":"Tao Zhang, Long Zhao, Renzhao Kuang","doi":"10.1159/000547276","DOIUrl":"https://doi.org/10.1159/000547276","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to elucidate the effect and mechanism of hyperoside on blood-brain barrier (BBB) damage in bacterial meningitis (BM) by regulating the microRNA-155 (miR-155)/brain-derived neurotrophic factor (BDNF) pathway.</p><p><strong>Methods: </strong>A rat model of meningitis was established via intracisternal injection of Streptococcus pneumoniae (SPN), while an in vitro BBB injury model was created by treating human cerebral microvascular endothelial cells (hCMEC/D3) with lipopolysaccharide (LPS). Hyperoside was administered in both models. Evans blue staining assessed BBB permeability in rats. Brain water content was determined using the wet-dry weight method. Transendothelial electrical resistance (TEER) was measured with an endothelial resistance meter. RT-qPCR, Western blot (WB), and ELISA assessed the expression of tight junction proteins in brain tissues and cell supernatants. ELISA was also used to measure inflammatory cytokine in cerebrospinal fluid and cell culture supernatants. Bioinformatics analysis and dual-luciferase reporter assays validated the regulatory relationship between miR-155 and BDNF.</p><p><strong>Results: </strong>Hyperoside treatment reduced BBB permeability, alleviated brain edema, and suppressed inflammatory cytokine expression in SPN-infected rats. In LPS-induced hCMEC/D3 cells, hyperoside significantly increased TEER values. Hyperoside markedly downregulated miR-155 and upregulated BDNF expression. miR-155 directly targeted BDNF and negatively regulated its expression in hCMEC/D3 cells. Importantly, the administration of a miR-155 mimic or BDNF knockdown (sh-BDNF) partially reversed the protective effects of hyperoside on TEER, tight junction protein expression (ZO-1, claudin-5, AQP4), and inflammatory cytokine levels (TNF-α, IL-1β, IL-6) in LPS-induced hCMEC/D3 cells.</p><p><strong>Conclusion: </strong>Hyperoside mitigates BBB damage in BM via reducing miR-155 expression and upregulating BDNF expression, leading to an increase in tight junction-related protein expression, a reduction in inflammatory factor secretion, and a decrease in BBB permeability.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-21"},"PeriodicalIF":3.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575922","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":"Smoking adversely affects survival of metastatic lung carcinoid patients: analysis of a large international audit and prognostic models for metastasis-free survival and overall survival.","authors":"Amy Clarke, Aimee Cunningham, Alejandro Garcia-Alvarez, Laura Spurgeon, Robert Morgan, Ana Carmona Alonso, Jorge Hernando, Jaume Capdevila, Alison Backen, Luca Giovanni Campana, Prakash Manoharan, Arpana Verma, Graham M Lord, Anshuman Chaturvedi, Was Mansoor, Sara Valpione","doi":"10.1159/000547192","DOIUrl":"https://doi.org/10.1159/000547192","url":null,"abstract":"<p><strong>Introduction: </strong>Among neuroendocrine lung cancers, lung carcinoids (LC, further divided into typical [TC] and atypical [AC]) are rare, representing only the 2% of all bronchopulmonary malignancies, and lack prognostic classification and stratification.</p><p><strong>Methods: </strong>We audited two international cohorts of patients with a confirmed diagnosis of LC for prognostic analysis. We used data from The Christie Hospital (Manchester, UK; N=282) and validated our findings using the cohort of Vall d'Hebron Hospital patients (Barcelona, Spain, N=80). We analysed patient data to identify a prognostic model for metastasis-free survival (MFS) and stage IV overall survival (OS).</p><p><strong>Results: </strong>Serum lactic dehydrogenase (LDH) concentration, stage, gender and tumour Ki-67% were significant at multivariable analysis (stratified for stage) for MFS after surgery (C-index=0.76, P<0.001), while histological subtype (TC vs AC) and other clinical variables were not. Independent prognostic factors for OS from onset of metastases included smoking history, along with known factors (patient age, proliferation index, FDG PET maximum SUV). The model C-index was 0.77 (P<0.001), with good concordance when applied to the external validation from Vall d'Hebron (C-index=0.94). Previously undescribed, patients with smoking history lived shorter (median OS=34 months vs not reached, P<0.0001), and the median OS could be shorter in current smokers (26.2 months) compared to ex-smokers (35.3 months).</p><p><strong>Conclusion: </strong>We provide a novel prognostic tool to estimate patient risk, clinical trial stratification and assist clinical decisions in the rarest lung tumours. We also describe for the first time that smoking history is an independent prognostic factor for OS in stage IV.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-18"},"PeriodicalIF":3.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554010","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":"Nociceptin-Opioid-Related Nociceptin Receptor 1 Signaling Partly Mediates Glucoprivic Suppression of Luteinizing Hormone Pulses in Female Rats: Arcuate Kiss1 Neurons as a Possible Target for Nociceptin.","authors":"Marina Takizawa, Koki Yamada, Mayuko Nagae, Shunsuke Seki, Sena Matsuzaki, Masumi Hirabayashi, Naoko Inoue, Yoshihisa Uenoyama, Hiroko Tsukamura","doi":"10.1159/000546766","DOIUrl":"10.1159/000546766","url":null,"abstract":"<p><strong>Introduction: </strong>During malnutrition, mammalian reproductive functions are suppressed by inhibition of the pulsatile release of gonadotropin-releasing hormone (GnRH)/gonadotropins. This study aimed to investigate whether nociceptin-opioid-related nociceptin receptor 1 (OPRL1) signaling mediates glucoprivic suppression of luteinizing hormone (LH) pulses in female rats.</p><p><strong>Methods and results: </strong>RNA sequencing analysis of tdTomato-positive arcuate (ARC) kisspeptin neurons obtained from Kiss1 (kisspeptin gene)-Cre/Cre-dependent tdTomato reporter female rats showed that Oprl1 messenger RNA expression was evident in ARC kisspeptin neurons. Double in situ hybridization for Kiss1 and Oprl1 or prepronociceptin gene (Pnoc) revealed that approximately 20% of Kiss1-expressing cells co-expressed Oprl1, but not Pnoc in ovariectomized (OVX) wild-type rats treated with diestrus levels of estradiol-17β (low E2). Administration of [N-Phe1]-orphanin FQ (1-13) amide (NC13), a selective OPRL1 antagonist, to the third ventricle (3V) transiently reversed the suppression of LH pulses induced by intravenous (iv) 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, in OVX + low E2 rats. The frequency of LH pulses during the first hour of the 3-h sampling period was significantly higher in 3V NC13-treated rats than in vehicle-treated controls. In contrast, 3V NC13 administration failed to affect LH pulses in OVX + low E2 rats without iv 2DG treatment. Furthermore, iv 2DG treatment significantly increased the percentage of fos-positive ARC Pnoc-expressing cells in OVX + low E2 rats.</p><p><strong>Conclusion: </strong>These results indicate that ARC nociceptin-OPRL1 signaling partly mediates the glucoprivic suppression of LH pulses and that nociceptin may directly suppress ARC kisspeptin neurons, the GnRH/LH pulse generator in female rats.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302574","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":"Advances in Drug Treatments for Male Patients with Prolactinomas.","authors":"Da Peng Wang, Han Yang Zhou, Yan Zhang, Li Xue, Zhe Bao Wu","doi":"10.1159/000546443","DOIUrl":"10.1159/000546443","url":null,"abstract":"<p><strong>Background: </strong>Pituitary adenomas (PAs), the most common intracranial neuroendocrine tumors, are typically benign. Among them, prolactinomas - tumors that secrete prolactin - account for approximately 60% of all PAs and are characterized by hyperprolactinemia and potential mass effects. Significant epidemiological and clinical differences exist between male and female prolactinoma patients.</p><p><strong>Summary: </strong>Prolactinomas in male patients tend to be larger and more aggressive, presenting unique challenges in treatment and management. Although dopamine agonists (DAs) remain the first-line therapy, men exhibit higher rates of DA resistance compared to women. For refractory prolactinomas in males, alternative treatments include temozolomide (TMZ), immune checkpoint inhibitors (anti-PD-1/PD-L1 and anti-CTLA4), somatostatin receptor analogs, mTOR inhibitors, tyrosine kinase inhibitors, bevacizumab, and aromatase inhibitors. These therapies may provide greater benefits to men with refractory prolactinomas than to women.</p><p><strong>Key messages: </strong>Despite advancements, significant challenges and opportunities persist in managing male prolactinoma patients. Key areas requiring attention include early diagnosis, predicting drug responsiveness, understanding sex-specific molecular mechanisms, and developing novel therapeutic strategies. Large-scale clinical trials are crucial to further assess the efficacy and safety of these treatments in men. This review consolidates recent progress in medical therapies and management approaches for male prolactinoma patients.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-21"},"PeriodicalIF":3.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285775","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":"Prognosis of NETs has there been improvement over the last 30 years.","authors":"Dominique Clement, Debashis Sarker, Aviva Frydman, Andrzej Rak, Vina Soran, David C Llewellyn, Raj Srirajaskanthan","doi":"10.1159/000546613","DOIUrl":"https://doi.org/10.1159/000546613","url":null,"abstract":"<p><p>Neuroendocrine tumours (NETs) are uncommon tumours, initially described as \"Carzinoides\" over hundred years ago and had since then multiple changes in terminology and difference in consideration of benign or malignant tumours. There have been multiple subclassifications and definitions made by the World Health Organisation (WHO). Multiple studies suggest an increase in incidence and prevalence. There are three types of sources of information for these studies; national databases, regional databases or single centre studies. These different sources of data describe small or larger cohorts of patients with NETs, include risks of bias and concerns regarding accuracy of data. The studies aim to describe the prognosis of patients with NETs, using outcomes as overall survival (OS), progression free survival (PFS) and relative survival rate (RSR). There is a heterogeneity of studies including different patient populations, different study periods, different definitions and different outcomes of prognosis it is difficult to compare studies. This review aims to describe how the prognosis changed in the past thirty years for patients with NETs taken into account changes in treatment. During the past three decades new treatments including targeting somatostatin receptors with somatostatin analogues (SSAs) or peptide receptor radionucleide therapy (PRRT), systemic anti-cancer treatments with Sunitinib, Everolimus and Cabozantinib were developed. In this review the treatments and prognosis between 1990-2000 is described. Subsequently per decade 2000-2010, 2010-2020 and 2020-currently, new treatments and up to date studies regarding the prognosis are reviewed. To explain changes in prognosis of patients with NETs.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-17"},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199674","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":"Sensorimotor Development in Rat Neonates Exposed to 17-α-Hydroxyprogesterone Caproate: A Progestin Used in Obstetrics.","authors":"Paige L Graney, Evelyn L Sarno, Jessie E Miller, Christine K Wagner","doi":"10.1159/000546356","DOIUrl":"10.1159/000546356","url":null,"abstract":"<p><strong>Introduction: </strong>17-α-hydroxyprogesterone caproate (17-OHPC) is prescribed to pregnant individuals at risk for preterm birth during critical periods of fetal cortical maturation. Yet the potential long-term effects of 17-OHPC on neural and behavioral development in children are unknown. Nuclear progesterone receptor (PR) is expressed in all functional regions of rat cortex during development. The hypothesis that developmental exposure to 17-OHPC alters sensorimotor development was tested.</p><p><strong>Methods: </strong>Sensorimotor behaviors were observed in neonates administered 17-OHPC from the day of birth through postnatal day 11, and PR was quantified in cortex at P11.</p><p><strong>Results: </strong>17-OHPC administration resulted in a disruption in sensorimotor indicators of typical brain development, without affecting gross motor function. 17-OHPC-exposed rats had significantly fewer PR-immunoreactive nuclei in somatosensory cortex.</p><p><strong>Conclusions: </strong>These findings demonstrate that 17-OHPC exposure during critical periods of cortical development may impact sensorimotor development and cortical sensitivity to progestins, highlighting the need for further investigation on the clinical implications of this progestin.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120307","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":"A New Bihormonal Model for the Brain Regulation of Gonadotropins in Teleosts.","authors":"Chinelo Nnenna Uju, Umar Farouk Mustapha, Suraj Unniappan","doi":"10.1159/000546403","DOIUrl":"10.1159/000546403","url":null,"abstract":"<p><strong>Background: </strong>The brain-pituitary-gonadal tissues play a key role in the neuroendocrine regulation of reproduction in vertebrates. Brain hormones, especially gonadotropin-releasing hormone (GnRH) is considered an important stimulant of gonadotropins (luteinizing hormone and follicle-stimulating hormone) released from the anterior pituitary. The current concept proposes a single brain hormone (GnRH) stimulating the release of both gonadotropins in fish and mammals. However, two articles published in 2024 proposed a dual-hormone concept in the brain regulation of gonadotropins in female medaka and zebrafish.</p><p><strong>Summary: </strong>The emerging concept proposes GnRH as the LH releasing hormone (LH-RH), and a second hormone, cholecystokinin (Cck), as the FSH-releasing hormone (FSH-RH) in these species. The two studies discussed here found that Cck is a potent FSH-RH. The line of evidence from the first study to support this notion includes the abundance of Cck receptors in the anterior pituitary Fsh-producing gonadotrophs, and severe reproductive defects in female medaka that genetically lacks Cck receptor 2. The second study used zebrafish, and found hypothalamic expression of Cck, anterior pituitary abundance of Cck receptors, and an all-male phenotype when Cck receptor 2 was knocked out. In both studies, Cck was found to be a more potent stimulant of intracellular Ca2+, when compared to GnRH effects.</p><p><strong>Key messages: </strong>These evidence from two independent studies indicate that Cck is a potent FSH-RH, and GnRH is the LH-RH, and supports a bihormonal model for the regulation of gonadotropin secretion from teleost pituitary. However, whether Cck elicits FSH-RH effects in other fish species remains unknown. In addition, the role of other hormones in the diverse endocrine milieu that regulate reproduction in modulating the phenotype seen in Cck receptor deficient fish warrants further consideration.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-9"},"PeriodicalIF":3.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120305","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}