Neuroendocrinology最新文献

{"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":"https://doi.org/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 mRNA 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 were 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":"1-19"},"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}

{"title":"Craniopharyngioma, Rathke Cleft Cyst, and Empty Sella Natural History and Endocrine Outcome in Pediatric Age: A Single Tertiary Center Experience over the 2000-2024 Period.","authors":"Gerdi Tuli, Jessica Munarin","doi":"10.1159/000546493","DOIUrl":"10.1159/000546493","url":null,"abstract":"<p><strong>Introduction: </strong>Craniopharyngioma (CP), Rathke cleft cyst (RCC), and empty sella (ES) are clinical conditions that may lead to endocrine disorders.</p><p><strong>Methods: </strong>Clinical data of all pediatric patients aged 0-18 years with diagnosis of CP, RCC, or ES, referred to our department over the period 2000-2024 were analyzed.</p><p><strong>Results: </strong>Data of 13 subjects with CP, 35 subjects with RCC, and 32 patients with ES were analyzed. Mean age at diagnosis was 6.6 ± 1.2 years in the CP group, 8.45 ± 3.2 years in the RCC group, and 10.55 ± 2.1 years in the ES group (p = 0.03). Prior endocrine disorder was the reason for requesting MRI in 27/80 patients: 1/13 of patients with CP, 16/35 of those with RCC, and 10/32 of patients with ES (p = 0.04). Among RCC patients, higher age and RCC size were observed in subjects with endocrine disorders (p = 0.04). Similar trend was observed in patients with ES, with significantly higher age in those with endocrine disorders compared to those without (p = 0.04). During follow-up, endocrine disorders were diagnosed in all patients with CP (13/13; 100%), in 5 out of 20 patients with RCC (25%), and in none of the patients with ES.</p><p><strong>Conclusion: </strong>CP, RCC, and ES need baseline and over a prolonged period of time endocrinological and neuroradiological follow-up, in order to detect promptly endocrine defects and sellar/suprasellar region alterations, and multidisciplinary follow-up in tertiary centers is mandatory.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-6"},"PeriodicalIF":3.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102275","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":"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":"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>Summary: </strong>Using protocol-driven search terms, Embase and Ovid were searched in July 2024. The search identified 2,041 unique citations, of which 66 articles were subsequently included. 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>Key messages: </strong>Significant data heterogeneity across studies poses challenges to comparability between studies and hinders 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 a greater number of population-based studies are needed. Future research should also focus on addressing 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":"1-24"},"PeriodicalIF":3.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176355/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Existence of Coexpressive Role of Kisspeptin and Insulin-2 in the Regulation of Luteinizing Hormone in Chronic Stress-Induced Polycystic Ovarian Syndrome-Like Phenotype in Rattus norvegicus.","authors":"Nitin K Rajashekara, Bindu Jayashankaraswamy, Raghu Nataraj","doi":"10.1159/000546126","DOIUrl":"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 the PCOS condition. This contradiction has led to several independent research studies assessing the role of metastatic suppressor genes Kisspeptin (KiSS1) and Insulin (INS2) in regulating LH by acting upon GnRH. The current study demonstrates the coexpressive 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, 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 preclinical Rattus norvegicus models.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158408/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}