Journal of Neuroendocrinology最新文献

{"title":"Metabolic-endocrine correlates of gut-brain axis mediators in polycystic ovary syndrome: A case-control study.","authors":"Rohina Bashir, Mir Asrar, Saloni Kamboj, Aadil Yousuf, Tasleem Arif, Nusrat Jahan, Mohd Ashraf Ganie","doi":"10.1111/jne.70180","DOIUrl":"https://doi.org/10.1111/jne.70180","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is increasingly recognized as a neuro-metabolic disorder involving disrupted signaling between the brain-gut axis and reproductive system. Peptides such as kisspeptin, ghrelin, serotonin, and peptide tyrosine tyrosine (PYY) are emerging as integrators of metabolic and endocrine function, yet their coordinated alterations in PCOS and relevance to metabolic risk remain underexplored. Therefore, we investigated the combined pattern of serum kisspeptin, ghrelin, serotonin, and PYY in PCOS, and their associations with metabolic and hormonal indices. In this case-control study, a total of 190 women aged 18-40 years were included between June 2023 and June 2024, comprising 96 women diagnosed with PCOS according to 2003 Rotterdam criteria and 94 age-matched healthy controls. Serum levels of kisspeptin, ghrelin, serotonin, and PYY were measured using ELISA. Secondary assessments included clinical, metabolic, hormonal, and inflammatory parameters. Women with PCOS had significantly higher serum kisspeptin levels and lower ghrelin and serotonin levels compared to controls (p < .05), while PYY levels were similar between the groups. Kisspeptin was inversely correlated with ghrelin (r = -.237, p = .003) and serotonin (r = -.303, p < .001). These peptides also showed significant associations with metabolic indices such as fasting insulin, glucose, HOMA-IR, triglyceride-glucose (TyG), and TyG-BMI ratios. In regression models adjusted for BMI, lower ghrelin (OR = 0.661, p = .008) and serotonin (OR = 0.814, p = .016) levels were independently associated with higher odds of PCOS. Exploratory receiver operating characteristic (ROC) analysis showed that kisspeptin demonstrated moderate discriminatory performance for PCOS (AUC = 0.768; 95% CI: 0.696-0.839), with 82.4% sensitivity and 59% specificity, whereas ghrelin, serotonin, and PYY showed lower AUCs, reflecting limited stand-alone discriminatory ability. Elevated kisspeptin with concomitant reductions in ghrelin and serotonin define a reproducible peptide signature in PCOS, linking neuroendocrine perturbations to measurable metabolic risk, independent of obesity. While kisspeptin shows greater biological separation between groups, none of the peptides alone are sufficient for diagnostic classification; instead, they indicate the central role of hypothalamic-gut axis dysfunction, particularly in lean PCOS phenotypes.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 5","pages":"e70180"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural variability across the transition to motherhood: Enhanced moment-to-moment neural variability during mentalizing in first-time mothers.","authors":"Sara Halmans, Milou Straathof, Sophie van 't Hof, Damiaan Denys, Eveline A Crone, Kristoffer N T Månsson, Elseline Hoekzema","doi":"10.1111/jne.70191","DOIUrl":"https://doi.org/10.1111/jne.70191","url":null,"abstract":"<p><p>Pregnancy is known to induce profound structural adaptations in the female brain, especially in regions involved in social cognition. This pre-conception cohort fMRI study examined changes in neural signal variability and functional connectivity during mentalizing tasks among 110 women (M_age = 30.5 years, SD = 3.5, range = 25-41), including 40 first-time mothers, 30 s-time mothers, and 40 nulliparous control women. Participants completed a mentalizing task before and after pregnancy, and, for a subset, 1 year postpartum. First-time mothers exhibited increased neural variability in response to child-related stimuli in the early postpartum period relative to their pre-conception baseline, whereas control women and second-time mothers showed decreases consistent with typical age-related changes. In controls, decreased neural variability correlated with declines in mentalizing task performance, suggesting that neural variability supports flexible and effective cognitive processing. Effects were stimulus- and parity-specific, with first-time mothers showing selective increases to child-related cues and second-time mothers showing distinct changes in adult-related processing. These findings suggest that pregnancy, particularly in first-time mothers, selectively preserves or enhances neural flexibility for processing infant social cues and that neural variability is a key marker of these adaptations.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 5","pages":"e70191"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Capillary connections between sensory circumventricular organs and adjacent parenchyma enable local volume transmission\".","authors":"","doi":"10.1111/jne.70192","DOIUrl":"https://doi.org/10.1111/jne.70192","url":null,"abstract":"","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 5","pages":"e70192"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arcuate nucleus-specific progesterone receptor knockdown in female mice is sufficient to induce PCOS-like hyperactivity in the reproductive axis","authors":"Kelly A. Glendining,&nbsp;Melanie Prescott,&nbsp;Kyoko Potapov,&nbsp;Elodie Kip,&nbsp;Rebecca E. Campbell","doi":"10.1111/jne.70181","DOIUrl":"10.1111/jne.70181","url":null,"abstract":"<p>Mammalian reproductive function is dependent upon gonadal steroid hormone feedback within the hypothalamic–pituitary–gonadal (HPG) axis. In polycystic ovary syndrome (PCOS), impaired progesterone (P4) negative feedback leads to hyperactive pulsatile secretion of luteinising hormone (LH) and impaired reproductive function. Although the precise upstream neuronal network modulating P4 negative feedback remains undefined, gamma-aminobutyric acid (GABA)ergic neurons in the arcuate nucleus (ARC) have been implicated. To identify the critical location of P4 negative feedback, we knocked out progesterone receptors (PR) specifically from GABA neurons by genetic cross (VGAT-Cre; PR^fl/fl) or specifically from the arcuate nucleus by stereotaxic AAV-Cre delivery to PR^fl/fl mice and assessed HPG axis function. Females with GABA-specific PR knockout (GABAPRKO) exhibited delayed vaginal opening and fewer estrous cycles compared to controls, but LH pulse frequency and P4 negative feedback were unaffected. In contrast, females with AAV-Cre-mediated knockdown of PR specifically in the ARC exhibited increased LH pulse frequency in comparison to control and AAV-Cre off-target animals. ARC-specific PR knockdown also resulted in significantly decreased estrous cycle frequency, increased cycle length, reduced time spent in proestrus, and impaired P4 negative feedback, but no change in testosterone levels. These data show that reduced PR signalling in the ARC of adult female mice is sufficient to drive hyperactivity within the HPG axis and mimic some but not all reproductive features of PCOS. The subtle reproductive deficits in GABAPRKO may reflect compensatory mechanisms or the involvement of multiple neuronal phenotypes in P4 negative feedback. Together, this work supports the ARC as a critical site for P4 negative feedback regulation of the reproductive axis.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing the diagnosis of primary aldosteronism: The role of adrenal vein sampling and the need for high-expertise reference centers","authors":"Aura D. Herrera-Martínez,&nbsp;Ángel Rebollo-Román,&nbsp;Pablo Remón-Ruiz,&nbsp;María José Picón-César,&nbsp;Patricia Guirado-Peláez,&nbsp;Carmen Tenorio-Jiménez,&nbsp;Carlos López-Pereira,&nbsp;Manuel Aguilar-Diosdado,&nbsp;Marta Iturregui-Guevara,&nbsp;Viyey K. Doulatram-Gamgaram,&nbsp;Maria Eugenia Pérez-Montilla,&nbsp;Juan José Espejo-Herrero,&nbsp;Ma Ángeles Galvez-Moreno,&nbsp;Alfonso Soto-Moreno,&nbsp;the Neuroendocrine Group of the Andalusian Society of Endocrinology, Diabetes and Nutrition","doi":"10.1111/jne.70165","DOIUrl":"10.1111/jne.70165","url":null,"abstract":"<p>Adrenal vein sampling (AVS) is the cornerstone diagnostic procedure for subtype differentiation in primary hyperaldosteronism, guiding therapeutic decision-making and offering the possibility of curative surgery to a subset of patients. However, technical challenges limit its use, and success rates vary substantially across centers, restricting equitable access for all patients with primary hyperaldosteronism. To evaluate AVS success rates in major hospitals across Andalucía and to assess the clinical evolution of patients who underwent surgery, with the goal of identifying referral centers and optimizing patient care. A retrospective observational study was conducted across six centers in Andalucía. A total of 151 procedures were performed in 140 patients, with an overall success rate of 55.62%. Intercenter analysis revealed successful catheterization rates ranging from 25% to 75.5%. Among patients without a computed tomography-detected adenoma, 27.4% demonstrated unilateral or bilateral aldosterone secretion. In patients with a single adenoma, discordant lateralization was observed in 9.80%, and bilateral secretion in 11.76%. Half of the patients with bilateral adenomas exhibited unilateral secretion. In total, discordant results reached 21.57%. Following surgery, all patients with successful AVS discontinued potassium supplementation, accompanied by a significant reduction in antihypertensive medication requirements (<i>p</i> &lt; .001). There were no significant differences among patients that underwent unilateral adrenalectomy based on imaging or AVS. Surgical management of primary hyperaldosteronism leads to significant clinical improvement, which is most accurately achieved when guided by successful AVS. Identifying and supporting expert centers is essential to improve access to AVS and enhance clinical outcomes for patients with primary hyperaldosteronism.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging role of chemokines and chemokine receptors in the biological and clinical behaviour of pituitary neuroendocrine tumours: An exploratory transcriptomic study","authors":"Ana Luísa Silva,&nbsp;Sayka Barry,&nbsp;Ana Hipólito,&nbsp;Mariana de Griné Severino,&nbsp;Rita Joaquim,&nbsp;Charlotte Hall,&nbsp;Tiago Oliveira,&nbsp;Dolores López-Presa,&nbsp;Gonçalo Borrecho,&nbsp;Francisco Tortosa,&nbsp;Ema Nobre,&nbsp;Claudia C. Faria,&nbsp;Márta Korbonits,&nbsp;Pedro Marques","doi":"10.1111/jne.70184","DOIUrl":"10.1111/jne.70184","url":null,"abstract":"<p>The chemokine network in the microenvironment of pituitary neuroendocrine tumours (PitNETs) may modulate tumour biology, aggressiveness, and treatment responses. We aimed to study the role of various chemokines and chemokine receptors in defining PitNET phenotype and clinical outcomes. We included 96 patients (51 females) with available snap-frozen PitNET tissue from surgery between 2014 and 2020. Chemokine and chemokine receptors were studied by RT-qPCR. Fold difference in mRNA expression was calculated using the ΔΔCt method; chemokine and receptor expression levels were normalised to the expression of the control gene <i>TBP</i>, and expressed relative to a reference sample. Ten chemokines and receptors were studied (<i>CCL2</i>, <i>CCL3</i>, <i>CCL4</i>, <i>CXCL8</i>, <i>CX3CL1</i>, <i>CCR2</i>, <i>CCR4</i>, <i>CCR5</i>, <i>CXCR1</i>, <i>CXCR2</i>), and their expression correlated with clinico-pathological and outcome data, as well as other available microenvironment-related data. We found strong positive correlations between all chemokines and chemokine receptors. Higher chemokine and receptor expression levels were seen in patients who had pituitary apoplexy (<i>CCR2</i>, <i>CXCR1</i>), hypopituitarism at diagnosis (<i>CCL2</i>, <i>CCR4</i>), Ki-67 &gt;3% (<i>CCL4</i>, <i>CXCR2</i>), as well as in patients who required re-operation (<i>CCL3</i>, <i>CXCL8</i>, <i>CXCR2</i>), multimodal therapy (<i>CCL2</i>), and had active disease at last-follow-up (<i>CCL2</i>). There was a positive correlation between the number of pituitary surgeries and expression levels of <i>CCL3</i>, <i>CXCL8</i>, <i>CX3CL1</i>, <i>CXCR1</i>, and <i>CXCR2</i>. Compared to nonfunctioning-PitNETs, somatotropinomas had higher expression of <i>CCL2, CCL4</i>, and <i>CCR2</i>, and lower expression of <i>CX3CL1</i> and <i>CCR4</i>. Expression of <i>CDH1</i> (encoding E-cadherin) correlated negatively with <i>CCL2</i>, <i>CCL4</i>, <i>CCR2</i>, <i>CCR4</i>, and <i>CXCR2</i>, while the expression of <i>ZEB1</i> (mesenchymal marker) positively correlated with <i>CCL3</i>, <i>CCL4</i>, and <i>CX3CL1</i>. PitNETs expressing higher levels of <i>CCL4</i>, <i>CX3CL1</i>, <i>CCR4</i>, <i>CCR5</i>, and <i>CXCR1</i> had more and bigger vessels. Somatotropinomas treated pre-operatively with somatostatin analogues were associated with higher expression of <i>CCL2</i>, <i>CCR4</i>, <i>CXCR1</i>, and <i>CXCR2</i>, while nonfunctioning-PitNETs pre-surgically treated with dopamine agonists were associated with lower expression of <i>CCL3</i>, <i>CCL4</i>, <i>CX3CL1</i>, <i>CCR5</i>, <i>CXCR1</i>, and <i>CXCR2</i>. Our data suggests that chemokines and chemokine receptors may be involved in the modulation of different tumorigenic mechanisms in PitNETs, including tumour proliferation, epithelial-to-mesenchymal transition, and angiogenesis, and may be associated with more aggressive and difficult-to-treat disease.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of gonadectomy and hormone replacement on habenula-induced dopamine inhibition in female and male rats","authors":"Vaughn J. Waldron,&nbsp;Monnette Suttawireesan,&nbsp;Shanzay Fatimah,&nbsp;Istvan J. Merchenthaler,&nbsp;P. Leon Brown","doi":"10.1111/jne.70183","DOIUrl":"10.1111/jne.70183","url":null,"abstract":"<p>Sex differences have been noted in the prevalence and severity of several neurological and mental health disorders. Midbrain dopaminergic activity is implicated in the etiology of many of these disorders and therefore may also contribute to some commonly seen sex differences in presentation and treatment. The ability of the lateral habenula to inhibit midbrain dopamine firing activity is reduced in female rats, and we test here the hypothesis that circulating gonadal hormones contribute to this sex difference. In vivo, single unit, extracellular recordings of dopamine neurons were conducted in female and male rats that were intact, gonadectomized, or had hormone replacement. Both spontaneous and habenula-evoked activities were recorded. In accordance with previous findings, we found that habenular stimulation produces profound inhibition in dopamine neurons that is of longer duration in male rats than female rats. There was no effect of gonadectomy on duration of inhibition in either males or females. Although there was a trend toward stronger rebound excitation in control male rats, there was no significant effect of gonadectomy in either the male or female rats. Here we show that circulating gonadal hormones have no apparent effect on habenular evoked dopamine inhibition. We discuss the limitations of the current study, including the possibility that the influence of circulating gonadal hormones may be limited to sub-populations of midbrain dopamine neurons.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"European Society of Neuroendocrine Tumors (ENETS) 2025 guidance paper for lung and thymic carcinoids","authors":"Eric Baudin,&nbsp;Alice Durand,&nbsp;Wieneke Buikhuisen,&nbsp;Jaume Capdevila,&nbsp;Martyn Caplin,&nbsp;Christophe M. Deroose,&nbsp;Clarisse Dromain,&nbsp;Antongiulio Faggiano,&nbsp;Pier Luigi Filosso,&nbsp;Gregory Kaltsas,&nbsp;Marco Volante,&nbsp;Thomas Walter,&nbsp;Rocio Garcia-Carbonero","doi":"10.1111/jne.70174","DOIUrl":"10.1111/jne.70174","url":null,"abstract":"<p>This ENETS guidance paper, developed by a multidisciplinary working group, provides up-to-date and practical advice on the diagnosis and management of lung and thymic carcinoids, based on recent developments and study results. These recommendations aim to provide practical recommendations for the diagnosis, treatment and follow-up of these tumours, and pave the road for more standardised care for our patients expecting improved outcomes. This paper is structured on a question-answer format in order to address common dilemmas encountered in clinical practice, including controversial issues and areas of uncertainty, based on the best available evidence and expert opinion when good quality evidence is not available. Each recommendation will provide a level of evidence and grade of recommendation as per the GRADE system (adapted from the Infectious Disease Society of United States Public Health Service grading system).</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of response and survival in metastatic paragangliomas and pheochromocytomas: Experience from two Spanish neuroendocrine tumor centers","authors":"M. I. del Olmo-García,&nbsp;J. E. Contreras Saldarriaga,&nbsp;L. Hernandez-Rienda,&nbsp;J. Hernando-Cubero,&nbsp;A. García Alvarez,&nbsp;A. García-Burillo,&nbsp;A. Casterás,&nbsp;A. Segura-Huerta,&nbsp;S. Prado,&nbsp;R. Palasí,&nbsp;J. F. Merino-Torres,&nbsp;J. Capdevila Castillón","doi":"10.1111/jne.70175","DOIUrl":"10.1111/jne.70175","url":null,"abstract":"<p>Metastatic pheochromocytomas and paragangliomas (mPPGLs) are uncommon, heterogeneous neuroendocrine tumors lacking standardized systemic treatment pathways. Evidence on treatment response predictors and outcome-based stratification remains limited. We conducted a retrospective study of 49 patients with mPPGLs treated between 2010 and 2024 at two Spanish referral centers. We evaluated clinical characteristics, systemic treatment patterns, radiologic responses (per RECIST), and survival outcomes. Patients were stratified into five clinical evolution patterns based on treatment response and disease trajectory. The most common indications for initiating systemic therapy were radiologic progression (59.5%) and high tumor burden (31%). First-line treatments included somatostatin analogues (SSAs, 40.5%), radionuclide therapies (33.3%: ¹⁷⁷Lu 9.5% and ¹³¹I-MIBG 23.8%), and chemotherapy (23.8%). Partial response rates were higher with chemotherapy, ¹³¹I-MIBG, and ¹⁷⁷Lu compared with SSAs. Tumor burden at treatment initiation appeared to be more closely associated with radiologic response than radiologic progression. Progression-free survival (PFS) appeared to differ according to first-line treatment type, with longer PFS observed in patients receiving radionuclide therapies. The median overall survival from systemic treatment initiation was 48 months. Five clinical evolution patterns were identified, highlighting disease heterogeneity. Radiologic progression remains the main trigger for systemic treatment in mPPGLs; however, initial tumor burden appears to be a stronger predictor of treatment response. Our proposed five-pattern clinical classification may contribute to prognostication and therapeutic individualization. Prospective studies are a key unmet need to determine the optimal timing and sequencing of systemic therapies in mPPGL.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal ganglion cell degeneration in glaucoma disrupts HPA axis temporal organization and dampens corticosterone production.","authors":"Pietra Souza Barsanele, Juliano Jefferson da Silva, Bryan Fellipe da Silva Cortes, Eliz Maria de Oliveira Furtado, José Cipolla-Neto, Leonardo Vinícius Monteiro de Assis, Maristela Oliveira Poletini, Maria Nathália Moraes","doi":"10.1111/jne.70182","DOIUrl":"https://doi.org/10.1111/jne.70182","url":null,"abstract":"<p><p>Glaucoma is a chronic optic neuropathy characterized by progressive vision loss. A previous study from our group showed that glaucoma-induced retinal degeneration disrupts photic signaling to the suprachiasmatic nucleus (SCN), altering the molecular components of the central circadian clock. Through its hypothalamic projections, the SCN entrains the hypothalamic-pituitary-adrenal (HPA) axis and drives the rhythmic secretion of corticosterone. In this study, we investigated whether central circadian clock disruption in glaucoma impacts the HPA axis and its downstream physiological rhythms. We analyzed the temporal profiles of key genes controlling the HPA axis in mice with glaucoma. The Crh gene expression was reduced in the paraventricular nucleus, while Crh-r1 exhibited a 10-h phase delay in the pituitary in response to glaucoma. Additionally, Pomc in the pituitary and Mc2r in the adrenal lost rhythmicity. The modulation of the daily rhythms of these key genes was associated with alterations in the diurnal rhythms of clock genes in the PVN, pituitary and adrenal gland. Glaucoma-induced phase shifts and amplitude alterations in the rhythmic expression of Per1, Per2, Nr1d1, and Bmal1 in the pituitary and adrenal gland, resulted in a temporal misalignment between the pituitary and adrenal rhythms. These molecular changes were associated with reduced corticosterone amplitude, suggesting impaired communication between central and peripheral clocks. Together, these findings demonstrate that glaucoma alters the temporal coordination of the HPA axis, highlighting how retinal dysfunction can propagate beyond the visual system to disturb systemic circadian and neuroendocrine regulation.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":"e70182"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}