Neuroendocrinology最新文献

{"title":"Unveiling the Prognostic Role of Synaptophysin in Conventional Colorectal Carcinomas.","authors":"Giovanna Sabella, Giovanni Centonze, Vincenzo Lagano, Andrea Scardino, Filiberto Belli, Giovanna Garzone, Carlotta Pardo, Daniela Galbiati, Sara Pusceddu, Alessandro Mangogna, Valentina Angerilli, Matteo Fassan, Andrea Vingiani, Luca Agnelli, Giancarlo Pruneri, Stefania Gobba, Silvia Uccella, Stefano La Rosa, Fausto Sessa, Carlo Capella, Massimo Milione","doi":"10.1159/000545979","DOIUrl":"https://doi.org/10.1159/000545979","url":null,"abstract":"<p><strong>Introduction: </strong>Although neuroendocrine differentiation in colorectal carcinomas (CRCs) has been extensively reported, the biological behavior of adenocarcinomas expressing synaptophysin (Syn) but lacking typical neuroendocrine morphology remains unclear.</p><p><strong>Methods: </strong>We tested 663 conventional CRCs with non-neuroendocrine morphology for Syn expression and correlated the results with clinicopathological and molecular characteristics as well as patient survival (overall survival [OS] and disease-free survival [DFS]). The survival characteristics of Syn expression group were compared to those of conventional CRCs and subsequently to those of 14 MiNENs.</p><p><strong>Results: </strong>Syn immunohistochemical expression ≥30% was confirmed in 27 (4.1%) patients and correlated with right colon site, grade 2, marked intratumoral lymphocyte infiltrate and BRAF p.V600E mutation. At univariate analysis variables associated with poor OS were 10-year increase in age (p=0.001), stage IIII-IV (p=0.001), Syn ≥30% (p=0.001), infiltrative growth (p=0.04) and residual tumor R1-2 (p=0.03). At multivariable analysis, Syn expression in ≥30% of gland-forming tumor cells emerged as an independent negative prognostic factor for both OS and DFS. Moreover 10-year increase in age, stage III-IV and Syn ≥30% (p<0.001) were associated with poor OS and marked peritumoral lymphocyte infiltrate with longer OS (p=0.02). Comparable results were obtained according to DFS; in addition, right colon site (p=0.04) was associated with longer DFS while KRAS mutation (p=0.04) was associated with poor DFS at univariate analysis. MiNEN patients showed a shorter DFS than all conventional adenocarcinomas with or without Syn expression in univariate analyses (p<0,001).</p><p><strong>Conclusions: </strong>Among conventional CRCs, we provided evidence that Syn expression is associated with worse OS and DFS and contributes to predicting clinical outcome. Future studies should explore the molecular mechanisms underlying the acquisition of the neuroendocrine phenotype to identify new targeted treatment strategies.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-28"},"PeriodicalIF":3.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034408","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 Sex and Deprivation on Neuroendocrine Tumour Survival: Challenges of Heterogeneous Data.","authors":"Ailbhe Lawlor, Harriet Wylde, Marie Line El Asmar, Benjamin Easton White, John Ramage, Mieke Van Hemelrijck, Beth Russell","doi":"10.1159/000546128","DOIUrl":"https://doi.org/10.1159/000546128","url":null,"abstract":"<p><strong>Background: </strong>For decades, the incidence of neuroendocrine tumours (NETs) has been steadily increasing. Existing research suggests that patient sociodemographic characteristics, such as sex and deprivation, may play a role in who survives a NET diagnosis. This systematic review identifies the available evidence assessing the impact of sex and deprivation on the prognosis of patients diagnosed with NETs.</p><p><strong>Methods: </strong>Using protocol-driven search terms, Embase and Ovid were searched in July 2024 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The identified studies were critically appraised using the Joanna Briggs Manual for Evidence Synthesis.</p><p><strong>Results: </strong>The search identified 2041 unique citations of which 66 articles were subsequently included. One study was excluded based on the critical appraisal. Findings were reported by geographical location. Included studies indicate a female survival advantage in North America and England, but the impact of sex on NET prognosis in wider European and Asian countries is less clear. The impact of deprivation on NET prognosis was assessed in North America, with one study conducted in Europe.</p><p><strong>Conclusions: </strong>Significant data heterogeneity across studies posed challenges for comparability between studies and hindered statistical analyses of these data. In North America and England, females diagnosed with NETs tend to survive longer than males. Existing single-centre studies do not provide conclusive evidence on the impact of sex on NET survival in Asian countries, and . While a greater number of population-based studies within Europe and Asia are needed., Ffuture research should also focus on addressing outcome heterogeneity across NET research to allow for more robust evidence synthesis, providing increased accuracy and generalisability of study results.  .</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-28"},"PeriodicalIF":3.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035983","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":"Existence of co-expressive role of Kisspeptin and Insulin-2 in the regulation of Luteinizing hormone (LH) in chronic stress-induced polycystic ovarian syndrome (PCOS)-like phenotype in Rattus norvegicus.","authors":"Nitin K Rajashekara, Bindu Jayashankaraswamy, Raghu Nataraj","doi":"10.1159/000546126","DOIUrl":"https://doi.org/10.1159/000546126","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is an ill manifestation of the normal ovarian function that obstructs folliculogenesis. Clinically, patients diagnosed with PCOS possess chronic psychological distress with the downregulated hypothalamus-pituitary-gonadal (HPG) axis under the influence of cortisol, but, in contrast, studies done elsewhere have demonstrated an increased hypothalamus-pituitary activity under PCOS condition. This contradiction has led to several independent research studies assessing the role of metastatic suppressor gene Kisspeptin (KISS1), and Insulin (INS2) in regulating LH by acting upon GnRH. The current study demonstrates the co-expressive role of KiSS1 and INS2 in regulating LH and monitoring ovarian health.</p><p><strong>Methodology: </strong>PCOS-like features were induced in the rats by a chronic stress regime, and the parameters were established. Another stress group of animals was dosed with 60 mg/kg body weight of ketoconazole before the stress exposure, and the parameters of the study were estimated and established.</p><p><strong>Results: </strong>The current study has observed that upon chronic stress exposure, the animals have exhibited all the features of PCOS like hyperandrogenism, cystic follicles with dysregulated estrous cyclicity, along with, an elevated LH, and decreased plasma insulin levels. As hypothesized, a 7-fold increase of KiSS1 expression and a 2-fold increase of INS-2 expressions have been observed in the stress group animals unlike the corticosterone inhibitor group of animals which have exhibited a controlled phenotype.</p><p><strong>Conclusion: </strong>The obtained relative fold changes in the gene expression level of both KiSS1 and INS2 reveal the association of stress with the pathology of PCOS via neuroendocrine regulation. The study has demonstrated the existence of a putative temporal coupling activity of KiSS1-INS2 expression-driven elevated LH in pre-clinical Rattus norvegicus models.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-26"},"PeriodicalIF":3.2,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021006","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":"Indirect Effect Model with Surge-Function for Describing Melatonin Circadian Rhythm: Quantitative Comparison and Application Between Normal Sleepers and Patients with Delayed Sleep-Wake Phase Disorder.","authors":"Zhanhui Lv, Zimo Zhang, Lu Wang, Sufeng Zhou, Jianguo Sun, Xiuqin Wang, Feng Shao","doi":"10.1159/000546125","DOIUrl":"https://doi.org/10.1159/000546125","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigates the circadian rhythm of melatonin in normal sleepers and delayed sleep-wake phase disorder (DSWPD) patients using quantitative pharmacology methods to better understand sleep disorders and their underlying mechanisms.</p><p><strong>Methods: </strong>We developed an indirect effect model incorporating a surge function using data from 10 normal sleepers and 26 DSWPD patients. Model accuracy and stability were evaluated using diagnostic plots, visual predictive check (VPC) and bootstrapping. Monte Carlo simulations (n=1000) quantitatively compared melatonin circadian rhythm characteristics between normal sleepers and DSWPD patients.  Finally, Bayesian estimation utilizing external data from 3 normal sleepers and 3 DSWPD patients predicted melatonin concentration at different time points and the dim light melatonin onset (DLMO).</p><p><strong>Results: </strong>An indirect effect model incorporating a surge function effectively described the circadian rhythm of endogenous melatonin. The model estimates a population typical value (relative standard error%) of: amplitude (AMP), 7.95 (15.47%); peak time (T0), 23:59 (4.13%); peak width (WID), 4.12 (5.78%); elimination rate constant (Kout), 1.23 h-1 (21.82%); baseline melatonin concentration (Baseline), 3.21 pg/ml (23.27%). Monte Carlo simulation revealed that DSWPD patients exhibited approximately 7-hour delay in DLMO, similar melatonin elimination rate constants, and a significantly lower melatonin production rate constants compared to normal sleepers. Bayesian estimation of the melatonin circadian characteristics and DLMO in DSWPD patients closely matched actual data, with model-estimated DLMO exhibiting an error margin within ±10%.</p><p><strong>Conclusion: </strong>Compared to normal sleepers, DSWPD patients exhibited a reduced rate of melatonin production, similar rate of melatonin elimination, and delayed DLMO, highlighting notable circadian melatonin profile alterations. The final model employed Bayesian feedback to estimate melatonin circadian rhythm characteristics and DLMO in DSWPD patients using sparsely sampled data.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-22"},"PeriodicalIF":3.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045024","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":"Gender perspective in Lung Neuroendocrine Tumors: a critical review.","authors":"Anna La Salvia, Roberta Modica, Francesca Spada, Roberta Elisa Rossi","doi":"10.1159/000546081","DOIUrl":"https://doi.org/10.1159/000546081","url":null,"abstract":"<p><strong>Background: </strong>The role of gender has gained attention in oncology. In the setting of lung neuroendocrine tumors (L-NETs) the existence of differences between male and females has been suggested, but no clear-cut data are available. We aim to provide a critical analysis of the existing literature regarding sex role in L-NETs.</p><p><strong>Methods: </strong>We performed an extensive search of the available literature to provide a critical narrative review focused on key topics as epidemiology, histopathological and molecular features, functioning syndromes, prognosis and response/toxicity to treatments in L-NETs according to sex.</p><p><strong>Results: </strong>Female patients are more likely to have a L-NET than males. The reasons underlying this gender differences are still unclear; a biologic mechanism for the sex difference is possible, through a role for hormones in regulating gene expression and promoting neuroendocrine cell proliferation. A difference in immunohistochemical biomarkers has been found; thyroid transcription factor-1 (TTF-1) expression appears to be associated with female gender; at molecular level in the majority of studies L-NET mutational profile is not stratified for sex. In terms of prognosis, a correlation between male gender and a more aggressive disease has been found. Patient's gender has been recognized as a key modulator in the response/resistance to anticancer treatments, however for L-NETs the available data regarding the activity of different treatments and their toxicities are scarce as in clinical trials designed for L-NETs a stratified evaluation of drugs' activity according to patients' sex is largely missing.</p><p><strong>Conclusions: </strong>There is emerging evidence suggesting a gender role in L-NETs, however further studies are needed to better understand the pathogenesis of these tumors and to plan tailored treatments.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040366","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":"Special Issue Advancements and Challenges in Neuroendocrine Tumor Research.","authors":"Patricia Borges de Souza, Massimiliano Mazza","doi":"10.1159/000545920","DOIUrl":"https://doi.org/10.1159/000545920","url":null,"abstract":"","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-3"},"PeriodicalIF":3.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute optogenetic activation of the subfornical organ produces sympathetically mediated increases in blood pressure.","authors":"Monique L Van Acquoy, Teodora Nedelkoska, Simon McMullan, Peter G R Burke, Cara M Hildreth","doi":"10.1159/000545849","DOIUrl":"https://doi.org/10.1159/000545849","url":null,"abstract":"<p><strong>Introduction: </strong>The subfornical organ (SFO) is a vital blood pressure-controlling region that elicits blood pressure changes likely via an excitatory (or glutamatergic) projection to the paraventricular nucleus (PVN). However, the role of this SFO-PVN pathway in blood pressure control has been poorly defined in the literature. As such, the present study aims to examine the functional connectivity between the SFO neurons and the PVN and how they intersect to control blood pressure.</p><p><strong>Methods: </strong>In Lewis rats (n = 10), glutamatergic SFO neurons (SFOglut) were transduced with ChannelRhodoposin via a CaMKIIa-promotor vector (pAAV9-CaMKIIa-hChR2(H134R)-EYFP). Under urethane anaesthesia, changes in blood pressure and renal and splanchnic nerve activities were recorded in response to photostimulation of SFOglut neurons before and after administration of an intravenous ganglionic blocker and V1a receptor antagonism and inhibition of the PVN via muscimol microinjection. Immunohistochemistry was used to examine the projections between the SFO and PVN.</p><p><strong>Results: </strong>Photostimulation of SFOglut neurons produced a frequency-dependent pressor response that was abolished by sympathetic ganglionic blockade, but not by inhibiting the vasoactive hormone vasopressin. This pressor response depends on ongoing neuronal transmission within the PVN as it is abolished by bilateral PVN inhibition. Confirming this, we found dense projections from SFOglut neurons to magnocellular and parvocellular PVN neurons. Finally, photostimulation of SFOglut neurons elicited a peak increase in sympathetic nerve activity that was reversibly abolished by phenylephrine administration and abolished by inhibition of the PVN, suggesting that the neuronal circuitry underpinning this response is barosensitive.</p><p><strong>Conclusion: </strong>The pressor response elicited by SFOglut neurons is largely mediated by barosensitive sympathetic nerve activity and dependent on the PVN.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-21"},"PeriodicalIF":3.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002984","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":"Upregulation of SSTR2 expression and radioligand binding of [18F]SiTATE in neuroendocrine tumour cells with combined inhibition of class I HDACs and LSD1.","authors":"Christoph J Auernhammer, Kathrin Zitzmann, Simon Lindner, Harun Ilhan, Peter Bartenstein, Umberto Maccio, Michael Orth, Lea Peischer, Julian Maurer, Gerald Spoettl, Katharina Wang, Christine Spitzweg, Alessa Fischer, Constanze Hantel, Ashley B Grossman, Felix Beuschlein, Karel Pacak, Svenja Nölting","doi":"10.1159/000545073","DOIUrl":"https://doi.org/10.1159/000545073","url":null,"abstract":"<p><strong>Introduction: </strong>Peptide receptor radionuclide therapy (PRRT) is a highly effective, targeted treatment option in advanced neuroendocrine tumours (NETs). However, NET patients expressing low levels of Somatostatin receptor type (SSTR)2 do not benefit from this powerful tool. Recently, several preclinical studies have revealed that histone deacetylase (HDAC) inhibitors can upregulate the expression of SSTR2 and enhance somatostatin ligand binding to tumour cells. In this preclinical study, we explored the effects of single and combined treatment of NET cells with the class I HDAC inhibitor entinostat and the lysine-specific demethylase 1 (LSD1) inhibitor CC-90011, on cell viability, SSTR2 expression and radioligand binding.</p><p><strong>Methods: </strong>The human NET cell lines BON1, NCI-H727, and QGP1 were treated with entinostat, CC-90011 or a combination of both. Cell viability was measured with a cell viability assay. SSTR2 expression was assessed by quantitative PCR, Western blot analysis, and immunohistochemistry. [18F]SiTATE uptake was investigated by a radioligand binding assay.</p><p><strong>Results: </strong>Treatment of NET cells with entinostat, CC-90011 and especially with the combination of both reduced tumour cell viability and strongly induced SSTR2 expression resulting in potently enhanced radioligand binding of [18F]SiTATE.</p><p><strong>Conclusion: </strong>Combined inhibition of class I HDACs and LSD1 potently increases SSTR2 expression and consequently radioligand binding and might thus be a putative strategy to improve the outcome of PRRT therapy in patients with NETs.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-25"},"PeriodicalIF":3.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795853","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 Effect of Metformin on Prolactin Concentration in Women with Hyperprolactinemia and Subclinical Hyperthyroidism.","authors":"Robert Krysiak, Karolina Kowalcze, Bogusław Okopień","doi":"10.1159/000545525","DOIUrl":"10.1159/000545525","url":null,"abstract":"<p><strong>Introduction: </strong>Because prolactin excess and hyperthyroidism are often complicated by hyperglycemia and impaired insulin sensitivity, many patients with both these disorders are treated with metformin. This drug inhibits secretory function of overactive anterior pituitary cells, including lactotrophs. The purpose of the current study was to investigate whether metformin action on prolactin oversecretion is impacted by coexisting hyperthyroidism.</p><p><strong>Methods: </strong>Our prospective, cohort study included two groups of women in reproductive age requiring metformin therapy with mild or moderate hyperprolactinemia. Patients with concomitant grade 1 subclinical hyperthyroidism (group A) and individuals without thyroid pathology (group B) were matched for age, insulin sensitivity, and total prolactin levels. Glucose homeostasis markers, thyroid-stimulating hormone (TSH), free thyroid hormones, total and monomeric prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, adrenocorticotropic hormone, IGF-1, and peripheral markers of thyroid hormone action (ferritin and osteocalcin) were measured before and after 6-month metformin therapy.</p><p><strong>Results: </strong>At baseline, both groups differed in levels of TSH, free thyroid hormones, ferritin, and osteocalcin. Although metformin reduced glucose, improved insulin sensitivity and reduced total and monomeric prolactin in both groups, these effects were more pronounced in group A than group B. The impact on prolactin in group A correlated with concentrations of free thyroid hormones. Only in group A, did metformin slightly increase FSH and LH concentrations. In women with hyperthyroidism and without thyroid pathology, there were no statistical differences between baseline and follow-up levels of the remaining variables.</p><p><strong>Conclusion: </strong>The study results suggest that hyperthyroidism potentiates the impact of metformin on secretory function of overactive lactotrophs in reproductive-age women.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-11"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753696","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":"Neurotrophic Effects of GH and GnRH in a Full Sciatic Nerve Transection Model in Male Rats.","authors":"Jorge J A Baca-Alonso, Denisse Calderón-Vallejo, Irma Hernández-Jasso, David Epardo, Jerusa E Balderas-Márquez, Maricela Luna, Carlos Arámburo, J Luis Quintanar, Carlos G Martínez-Moreno","doi":"10.1159/000545129","DOIUrl":"10.1159/000545129","url":null,"abstract":"<p><strong>Introduction: </strong>Peripheral nerve injuries, such as sciatic nerve transection (SNT), are often associated with significant sensory and motor deficits. Growth hormone (GH) and gonadotropin-releasing hormone (GnRH) have been shown to exert neurotrophic effects that can promote nerve regeneration and functional reinnervation. However, the combined impact of these hormones on peripheral nerve repair remains poorly understood.</p><p><strong>Methods: </strong>This study aimed to analyze the individual and combined effects of GH and GnRH in a rat model of SNT, using orchiectomized male rats to prevent steroid-mediated neuroregeneration and neuroprotection. Treatments included GH, GnRH, or a combination of both, with subsequent assessments of motor and sensory function, as well as histological and molecular analyses of the nerve tissue and associated muscles.</p><p><strong>Results: </strong>The results revealed that both GH and GnRH significantly enhanced nerve regeneration and neural function when administered individually. Treated animals exhibited improved axonal growth, myelination, and sensory and motor functional recovery. In addition, GH and GnRH reduced neuroinflammation/reactive gliosis, as evidenced by the downregulation of TNFα, IL-1β, Iba-1, and GFAP, which are typically elevated following nerve injury. These findings indicate that each hormone independently supports critical aspects of nerve repair and functional restoration after injury. Surprisingly, when GH and GnRH were administered together, their beneficial effects were not additive. Instead, the combination of the two treatments led to diminished outcomes in comparison to either treatment alone. Specifically, animals receiving the combined therapy showed reduced axonal organization, impaired myelination, and less functional improvement.</p><p><strong>Conclusion: </strong>GH and GnRH demonstrate considerable potential as individual therapeutic agents for promoting peripheral nerve regeneration, each providing significant benefits in terms of axonal growth, functional recovery, and reduction of neuroinflammation.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-23"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}