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Results for “Endocrine System”

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At least 19 recordsLinked to original sources

PubMed2026

ScRNA-seq analysis reveals the effects of nitrite stress on the endocrine system of the eyestalk in Litopenaeus vannamei.

Nitrite is a harmful substance generated in Litopenaeus vannamei farming systems, largely originating from the inadequate breakdown of surplus feed and shrimp feces. Its accumulation in the water can affect the growth and physiological functions of shrimp, damage the immune system, and even cause mass mortality, thus becoming a key environmental factor restricting the green development of the industry. Under nitrite stress, the eyestalk, as an important neuroendocrine regulatory center in crustaceans, participates in the stress adaptation of the organism and exerts a protective effect by regulating energy metabolism and immune function. However, the molecular regulatory mechanism of the eyestalk in response to nitrite stress remains unclear. In this study, single-cell RNA sequencing (scRNA-seq) technology was used to analyze the heterogeneity of eyestalk cells in L. vannamei under nitrite stress. A total of 18, 394 high-quality cells were obtained, and six major cell subpopulations, including Neurosecretory cell, Motor neuron, Sensory neuron, Interneuron, Neurogliocyte, and Support cell, were identified. Differential expression analysis identified 839 differentially expressed genes, and different cell types showed distinct specific responses to nitrite stress. Functional enrichment analysis indicated that pathways such as glycolysis, oxidative phosphorylation, ribosome function, and endoplasmic reticulum protein processing were significantly activated, while signal transduction and DNA repair-related pathways were inhibited. Further analysis revealed that nitrite stress could induce mitochondrial function changes and trigger oxidative stress, thereby affecting the neuroendocrine system function of the eyestalk. This study provided insights into transcriptomic responses of the eyestalk to nitrite stress at the single-cell level, laying a theoretical foundation for the management of aquaculture environments.

Animals↗

PubMed2026

Mechanic evaluation of Jisheng Shenqi Wan on calcium oxalate kidney stones: an integrated network pharmacology and metabolomics.

OBJECTIVE: To understand the efficacy of Jisheng Shenqi Wan (JSSQW, ) in treating calcium oxalate kidney stones (KS) and to investigate the mechanism of JSSQW action by combining network pharmacology with metabolomics analysis based on ultra-high performance liquid chromatography combined with tandem electrostatic field orbital trap high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS). METHODS: The chemical components of JSSQW absorbed into rat blood were identified by UHPLC-Q/Orbitrap HRMS. The identified components were introduced into the Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine platform to screen for target genes, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and disease enrichment analysis. A KS rat model was generated using the oxalic acid precursor method to examine the efficacy of JSSQW for treating KS. Serum metabolomics was used to monitor changes in endogenous substances in KS rats after JSSQW intervention. RESULTS: Twenty-three chemicals from JSSQW were identified in the blood of JSSQW gavage-administered rats. KEGG enrichment analysis predicted the top 20 signaling pathways affected by these 23 chemicals. Disease enrichment analysis showed that the target genes of these 23 chemicals were enriched in diseases of the urinary system and endocrine system, including kidney stones. In a KS rat model, JSSQW inhibited the aggregation of calcium oxalate crystals, reduced renal tubular injury, lowered the renal index, and improved biochemical indicators (blood creatinine, blood urea nitrogen). Serum metabolomics identified 25 differential metabolites that responded to JSSQW treatment. They were mainly lipids, with phosphatidylethanolamine and phosphorylcholine and their derivatives accounting for the highest proportion. Metabolic pathway analysis showed that the changes in differential metabolites were related to multiple metabolic pathways, especially sphingolipid metabolism and sphingolipid signaling pathways. CONCLUSIONS: JSSQW can inhibit the aggregation of calcium oxalate crystals in the kidneys, reduce tubular injury, and improve kidney function in KS rats. Its mechanism of action may be related to regulating disordered metabolites and metabolic pathways, especially glycerol phospholipid metabolism, sphingolipid metabolism, and sphingolipid signaling.

Drugs, Chinese Herbal↗

PubMed2026

Bisphenols and their role in female infertility and hormone-related cancer.

Various types of external chemicals can disrupt the endocrine system, interfering with normal hormone function and causing a broad spectrum of negative health effects. Endocrine-disrupting chemicals (EDCs) are a diverse group of natural and synthetic chemicals that are known to contaminate the environment. It is postulated that these agents can contribute to the development of many diseases, including infertility and cancer, because of their ability to interfere with estrogen receptors (ERs). Bisphenols (BPs) are a group of compounds that belong to EDCs, the most common of which is bisphenol A (BPA). Due to restrictions on the use of BPA in industry, analogues such as bisphenol S (BPS) and bisphenol F (BPF) have been introduced. However, some reports indicate that BPA analogues also have negative effects on the endocrine system in both humans and animals because of their structural similarity. This review summarises current knowledge related to BPA, its analogues and their role in female infertility and hormone-related cancers. Furthermore, this review also points to the problem of exposure to more than one estrogenic agent and highlights the importance of considering exposure to multiple chemicals when assessing health effects and setting daily limits.

Humans↗

PubMed2026

Exploring shared biomarkers and their mechanisms in thyroid cancer and systemic lupus erythematosus via bioinformatics analysis.

BACKGROUND: Systemic lupus erythematosus (SLE), an autoimmune disorder, is linked to a heightened risk of multiple malignancies, including thyroid cancer. Thyroid cancer is the most prevalent malignancy of the endocrine system, and its autoimmune-related pathological features render it an optimal subject for investigating the mechanisms of their comorbidity. The molecular mechanisms underlying this comorbidity are still ambiguous. The accurate diagnosis and treatment of thyroid cancer urgently necessitate innovative molecular targets that extend beyond conventional pathological characteristics. This study seeks to employ integrated bioinformatics approaches to elucidate potential shared molecular mechanisms and immunological features between thyroid cancer and systemic lupus erythematosus (SLE), aiming to enhance understanding of their comorbidity and identify novel intervention targets. METHODS: This study initially acquired gene expression data for TC and SLE from the GEO database and subsequently screened and identified differentially expressed genes (DEGs) shared by both diseases. Subsequently, we conducted Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome functional enrichment analyses on these 46 shared differentially expressed genes (DEGs) and further assessed the activation status of pertinent pathways using Gene Set Enrichment Analysis (GSEA). Subsequently, we employed CIBERSORTx to examine immune infiltration patterns and developed protein-protein interaction networks utilising the STRING database. We identified hub genes utilising the MCODE and cytoHubba plugins and visualised the findings with Cytoscape software. We additionally assessed the diagnostic efficacy of these core hub genes in an independent dataset utilising ROC curves and investigated their prognostic relevance in thyroid cancer through Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression. Ultimately, we employed the Network Analyst platform to forecast transcription factor-gene and miRNA-gene regulatory networks and identified potential targeted therapeutic compounds utilising the DSigDB database. RESULTS: This study identified 46 differentially expressed genes (DEGs) commonly linked to thyroid cancer and systemic lupus erythematosus (SLE), which were significantly enriched in signalling pathways associated with immune-inflammatory activation, type I interferon responses, and complement pathway activation. Moreover, GSEA findings validated that immune-inflammatory and autoimmune-related pathways are markedly activated in both conditions. Twelve hub genes were discerned through protein-protein interaction networks. Analysis of immune infiltration indicated that thyroid cancer and systemic lupus erythematosus exhibit a shared characteristic of innate immune dysregulation, marked by the infiltration of myeloid cells (neutrophils, M0/M2 macrophages). Receiver operating characteristic (ROC) curve analysis identified six significant core hub genes with substantial diagnostic value: C1QB, LCN2, C1QC, LTF, VSIG4, and C3AR1. Univariate survival analysis indicated that elevated expression of C1QC and C3AR1 significantly enhances overall survival in thyroid cancer patients; however, multivariate COX regression analysis revealed that their independent prognostic significance necessitates further validation. This study predicted the interaction networks of transcription factors and miRNAs regulating key genes, with LCN2 demonstrating the highest connectivity to miRNAs, and identified candidate therapeutic compounds linked to it. CONCLUSION: This study employed bioinformatics analysis to identify critical shared hub genes and molecular pathways connecting thyroid cancer and systemic lupus erythematosus, offering novel insights into their shared pathogenesis and the advancement of targeted biomarkers and therapeutic strategies.

Bioinformatics analysis↗

PubMed2025

Mouse Testing Methods in Psychoneuroimmunology: Measuring Behavioral Responses.

The field of psychoneuroimmunology (PNI) aims to uncover the processes and consequences of nervous, immune, and endocrine system relationships. Behavior is a consequence of such interactions and manifests from a complex interweave of factors including immune-to-neural and neural-to-immune communication. Often the signaling molecules involved during a particular episode of neuroimmune activation are not known, but behavioral response provides evidence that bioactives such as neurotransmitters and cytokines are perturbed. Immunobehavioral phenotyping is a first-line approach when examining the neuroimmune system and its reaction to immune stimulation or suppression. Behavioral response is significantly more sensitive than direct measurement of a single specific bioactive and can quickly and efficiently rule in or out relevance of a particular immune challenge or therapeutic to neuroimmunity. Classically, immunobehavioral research was focused on sickness symptoms related to bacterial infection, but neuroimmune activation is now a recognized complication of diseases and disorders ranging from cancer to diabesity to Alzheimer's. Immunobehaviors include lethargy, loss of appetite, and disinterest in social activity/surrounding environment. In addition, neuroimmune activation can diminish physical activity, precipitate feelings of depression and anxiety, and impair cognitive and executive function. Provided is a detailed overview of behavioral tests frequently used to examine neuroimmune activation in mice with a special emphasis on pre-experimental conditions that can confound or prevent successful immunobehavioral experimentation.

Animals↗

PubMed2025

Sample Preparation of Caenorhabditis elegans for GC-MS-Based Metabolomics in Toxicity Assessment.

The nematode Caenorhabditis elegans, widely recognized as a model organism due to its ease of breeding and well-characterized genomes, boasts complete digestive, reproductive, and endocrine systems, as well as conserved signaling pathways shared with mammals. It has become an invaluable resource for metabolomics research, particularly in examining responses to chemical or environmental factors and toxicity assessments. In this article, we provide detailed, step-by-step protocols for cultivating C. elegans and conducting metabolomics analyses, specifically focusing on sample preparation for GC-MS analysis in response to toxic compound treatments. We highlight the critical choice of extraction solvent, introducing two representative systems for extracting metabolites from C. elegans.

Animals↗

PubMed2026

Firemaster 550 differentially alters gene expression underlying synaptic function in amygdala of prairie voles after gestational or lactational exposure.

Neurodevelopmental disorders often share similar behavioral diagnostic criteria including socioemotional and cognitive deficits. The prairie vole is a uniquely suitable model to study these deficits because they demonstrate strong social affiliation, bi-parental care, and partner attachment. Previously, we have shown that developmental exposure to the flame-retardant mixture Firemaster 550 (FM 550) impairs socioemotional behavior in the prairie vole and alters underlying neuroanatomy and function. However, the mechanisms for impaired pair bonding in males and increased anxiety in females remain unknown, along with the specific critical window(s) of vulnerability. Herein, we exposed prairie vole dams to FM 550 during gestation or lactation, and performed bulk RNA-seq on the amygdala, a hub of socioemotional processing, in their adult offspring. Two mathematically orthogonal methods were utilized for analysis, a linear statistical method and an ensemble machine learning method, incorporating sex as a biological variable. Gene ontology (GO) pathway analysis was performed following both and results compared to identify potential mechanisms of toxicity. GO results indicated consistent expression changes in the Synapse cellular component in all conditions, and implicated glutamatergic signaling specifically. Additionally, gestational exposure (GE) altered genes underlying modulation of synaptic transmission and neural development, while lactational exposure (LE) impacted genes underlying synaptic plasticity, axon guidance, and mitophagy. Machine learning identified disruption of endocrine system development, regulation of biosynthetic processes in GE animals, and suppression of various neuroinflammatory genes across multiple groups. Finally, we performed RNA expression analysis using Nanostring and demonstrated stronger correlation with the differentially expressed genes (DEG) of interest in females than males. Overall, this study demonstrates both the intersecting and distinct impacts of FM 550 exposure on amygdalar gene expression depending on sex and timing of exposure.

Animals↗

PubMed2026

Mechanisms of Hexavalent Chromium-Induced Reproductive Toxicity: A Focus on the Ovary and Placenta.

Hexavalent Chromium (Cr(VI)) is a Group A carcinogen, mutagen, and teratogen. Cr(VI) has been used by more than 50 industries, and its contamination of drinking water is widespread across the United States (U.S.). Epidemiological data of women who lived in Willits, California, U.S., indicate that environmental exposure to Cr(VI) adversely affects pregnancy outcomes and the health of their immediate offspring, resulting in a low birth rate, pregnancy loss, and spontaneous abortion, and their children (F1 offspring) experienced birth defects. However, the molecular mechanisms behind Cr(VI)-induced reproductive and developmental toxicity are poorly understood. Cr(VI) enters cells through anion transporters and is rapidly reduced to Cr(III) by endogenous antioxidants within the cell. Cr(III) forms adducts with DNA, which can block DNA replication and transcription; abnormal repair can lead to DNA double-strand breaks, mutations, micronucleus formation, chromosomal abnormalities, and increased genomic instability. Cr(VI) induces oxidative stress via the Fenton reaction, generating free radicals, and depleting antioxidants, thereby promoting apoptosis via p53-dependent and independent pathways, resulting in follicular atresia and accelerated reproductive aging. Antioxidant supplementation with resveratrol, vitamin C, and edaravone mitigates Cr(VI) toxicity in the ovary. Cr(VI) disrupts meiosis in metaphase II oocytes by causing DNA strand breaks, altering F-actin dynamics, disturbing microtubules, and leading to chromosome missegregation. Gestational exposure to Cr(VI) also disrupts placental function through multiple mechanisms by targeting trophoblast lineages. The current review focuses on genotoxicity, oxidative stress, and other mechanisms by which Cr(VI) disrupts the female reproductive and endocrine systems, with particular emphasis on the ovary and placenta.

Hexavalent chromium↗

PubMed2025

Venus flytraps' metabolome analysis discloses the metabolic fate of prey animal foodstock.

Carnivorous plants such as the Venus flytrap Dionaea muscipula survive in nutrient-poor habitats by attracting and consuming animals. Upon deflection of the touch-sensitive trigger hairs, the trap closes instantly. Panicking prey repeatedly collides with trigger hairs, which activate the endocrine system: mechano- and chemosensors translate the information on the prey's nature, size, and activity into jasmonate-dependent lytic enzyme secretion. This digestive fluid gradually degrades its exoskeleton and internal tissues. The released substances are absorbed by glands covering the inner trap surface. To understand Dionaea's modification of metabolism upon prey consumption, we compared the metabolic profiles associated with secretion and insect feeding. In favor of digestive enzyme secretion, the abundance of most amino acids decreased after JA-stimulation without prey present. By contrast, insect feeding resulted in an increase in almost all amino acids within the trap. In agreement with the export of prey-derived nitrogen, the abundance of certain amino acids also increased in the petiole. In response to feeding with urea, chitin, nucleic acids, or phospholipids, the amino acid profile remained relatively unchanged. This might indicate that the alterations in the Venus flytrap's metabolism depend both on the type of substance and on its amount.

Droseraceae↗

PubMed2025

Transcriptomic profile induced by calcitriol in CaSki human cervical cancer cell line.

The vitamin D endocrine system, primarily mediated by its main metabolite calcitriol and the vitamin D receptor (VDR), plays a critical role in numerous human physiological processes, ranging from calcium metabolism to the prevention of various tumors, including cervical cancer. In this study, we comprehensively investigated the genomic regulatory effects of calcitriol in a cervical cancer model. We examined the transcriptional changes induced by calcitriol in CaSki cells, a cervical cell line harboring multiple copies of HPV16, the primary causal agent of cervical cancer. Our microarray findings, revealed that calcitriol regulated over 1000 protein-coding genes, exhibiting a predominantly repressive effect on the CaSki cell transcriptome by suppressing twice as many genes as it induced. Calcitriol decreased EPHA2 and RARA expression while inducing KLK6 and CYP4F3 expression in CaSki cells, as validated by qPCR and Western blot. Functional analysis demonstrated that calcitriol effectively inhibited key processes involved in cancer progression, including cell proliferation and migration. This was further supported by the significant downregulation of MMP7 and MMP13 mRNA levels. Our microarray results also showed that, in addition to its effects on protein-coding genes, calcitriol significantly regulates non-coding RNAs, altering the expression of approximately 400 non-coding RNAs, including 111 microRNA precursors and 29 mature microRNAs, of which 17 were upregulated and 12 downregulated. Notably, among these calcitriol-regulated microRNAs are some involved in cervical cancer biology, such as miR-6129, miR-382, miR-655, miR-211, miR-590, miR-130a, miR-301a, and miR-1252. Collectively, these findings suggest that calcitriol exhibits a significant antitumor effect in this advanced cervical cancer model by blocking critical processes for tumor progression, underscoring the importance of maintaining adequate vitamin D nutritional status.

Humans↗

PubMed2025

Systematic meta-analysis of the toxicities and side effects of the targeted drug lenvatinib.

BACKGROUND: Lenvatinib, an effective targeted drug for various cancers, has clinical medication safety concerns due to its toxicities and side effects. OBJECTIVE: This study evaluated lenvatinib-induced any adverse events (any AEs) and nine aspects: vascular toxicities related to the circulatory system (vascular toxicities, blood system, and heart), toxicities of the skin and its appendages (skin/subcutaneous tissue and taste system), toxicities of the respiratory system (respiratory, thoracic, and mediastinal and respiratory tract), toxicities of the nervous system (nervous system and general), toxicities of the digestive system (gastrointestinal and liver), toxicities of the urinary system, toxicities of the endocrine and metabolic system (endocrine and metabolism/nutrition), toxicities of the musculoskeletal system, and other severe toxicities. Toxicities and side effects were stratified by severity into any and ≥3 grades for analysis. PATIENTS/MATERIALS AND METHODS: Multiple databases were searched for lenvatinib cancer clinical studies (cohort studies and randomized controlled trials) from inception to December 31, 2024; toxicity and side effect data were extracted and analyzed. RESULTS: Nine high-quality studies were included, showing that lenvatinib is effective in cancers but has notable toxicities. Taking hypertension as an example, for any grade, the risk ratio (RR) was 2.34 with a 95% confidence interval (CI) of [2.09, 2.62], a Z-value of 14.74, and a P-value <0.00001; for grade ≥3, the RR was 2.60 with a 95% CI of [2.21, 3.06], a Z-value of 11.44, and a P-value <0.00001. CONCLUSION: Lenvatinib is effective for cancer but toxic, and this study supports its rational clinical use.

Humans↗

PubMed2022

FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit.

Excessive alcohol consumption is a major health and social issue in our society. Pharmacologic administration of the endocrine hormone fibroblast growth factor 21 (FGF21) suppresses alcohol consumption through actions in the brain in rodents, and genome-wide association studies have identified single nucleotide polymorphisms in genes involved with FGF21 signaling as being associated with increased alcohol consumption in humans. However, the neural circuit(s) through which FGF21 signals to suppress alcohol consumption are unknown, as are its effects on alcohol consumption in higher organisms. Here, we demonstrate that administration of an FGF21 analog to alcohol-preferring non-human primates reduces alcohol intake by 50%. Further, we reveal that FGF21 suppresses alcohol consumption through a projection-specific subpopulation of KLB-expressing neurons in the basolateral amygdala. Our results illustrate how FGF21 suppresses alcohol consumption through a specific population of neurons in the brain and demonstrate its therapeutic potential in non-human primate models of excessive alcohol consumption.

Alcohol Drinking↗

PubMed2025

Bi-allelic loss-of-function variants in POC5 cause a syndromic retinal, endocrine, and neuromuscular ciliopathy.

PURPOSE: A homozygous loss-of-function (LoF) variant in POC5 was previously described in an individual with retinitis pigmentosa. We identified POC5 variants in 12 probands with a syndromic phenotype. We aim to define the phenotype spectrum and molecular mechanism associated with biallelic POC5 LoF variants. METHODS: We studied a cohort of 12 families with bi-allelic LoF POC5 variants and performed detailed phenotype analysis. POC5 localization studies were performed in 3 proband-derived fibroblast cell lines. RESULTS: Detailed phenotyping of probands with POC5 variants expands the phenotype spectrum beyond ocular manifestations. This syndrome causes not only rod-cone dystrophy but also diabetes mellitus with severe insulin resistance and partial lipodystrophy, kidney disease, and muscle cramps. The POC5 protein plays an essential role during cell cycle and cilium formation. Interestingly, POC5 localization studies in 3 proband-derived fibroblast cell lines show aberrant localization suggesting a ciliary defect. The phenotypes of the 12 families in this study fit well within the ciliopathy phenotype spectrum, except for lipodystrophy, which is not common in ciliopathies. CONCLUSION: We describe a multiorgan syndrome caused by bi-allelic LoF variants in POC5. This underscores the pleiotropic effects of POC5 variants and highlights the significance of adipose tissue and metabolic dysfunction in ciliopathies.

Humans↗

PubMed2026

Arrhythmia and cardiomyopathy risk in Taiwan with complementary biobank evidence on thyroid genetic susceptibility: an integrative population-based framework.

BACKGROUND: Arrhythmia-induced cardiomyopathy (AiCM) is a potentially reversible cause of ventricular dysfunction; however, only a subset of patients with arrhythmia develop cardiomyopathy. Emerging evidence suggests that endocrine factors, particularly thyroid dysfunction with genetic susceptibility, may contribute to inter-individual variability in arrhythmia-related myocardial outcomes. METHODS: We performed a dual-cohort population-based study using the National Health Insurance Research Database (NHIRD, 2000-2015) and the Taiwan Biobank (TWB). In NHIRD, we examined the association between newly diagnosed arrhythmia and incident cardiomyopathy using Cox proportional hazards models. In TWB, genome-wide data, thyroid-stimulating hormone (TSH), polygenic risk scores (PRSs), lifestyle factors, and metabolic comorbidities were analyzed using multivariable regression and interaction models to assess determinants of thyroid dysfunction. RESULTS: In the NHIRD cohort, arrhythmia was associated with a significantly increased risk of incident cardiomyopathy (adjusted hazard ratio (aHR): 2.49, 95% CI: 1.94-2.96), with atrial fibrillation showing the strongest association among arrhythmia subtypes. In the TWB cohort, a higher thyroid polygenic risk score was strongly associated with thyroid dysfunction (adjusted odds ratio (aOR): 6.64, 95% CI: 5.86-7.52). The association between genetic susceptibility and thyroid dysfunction was further modified by metabolic and lifestyle factors, including diabetes, hyperlipidemia, and dietary patterns. Genome-wide analysis identified multiple loci associated with thyroid-stimulating hormone regulation, consistent with a polygenic architecture of thyroid endocrine traits. CONCLUSION: Arrhythmia was associated with an increased risk of cardiomyopathy in a nationwide cohort, while thyroid genetic susceptibility was strongly associated with thyroid dysfunction in a biobank cohort and modified by metabolic and lifestyle factors. These findings provide complementary population-level evidence of parallel cardiovascular and endocrine-genetic associations. Because the two cohorts were not individually linked, causal inference cannot be established. The results support a systems-level framework of endocrine-cardiac interaction and suggest that integrated clinical and genetic risk assessment may help identify individuals who warrant closer monitoring.

arrhythmia↗

PubMed2025

Celastrol modulates IRS1 expression to alleviate ovarian aging and to enhance follicular development.

Ovarian aging significantly contributes to the decline of the female reproductive system, adversely affecting fertility and endocrine homeostasis. To address the challenges posed by reproductive aging, natural products have shown promising preventive and therapeutic effects. Here, we investigated the beneficial effects of natural compound celastrol on ovarian development and aging, together with its underlying mechanisms. We found that celastrol administration at a concentration of 3 mg/kg promoted follicle development in young mice and enhanced porcine oocyte maturation, while regulating granulosa cell proliferation and apoptosis. In 12-month-old mice (equivalent to middle-aged adults), celastrol exhibited similar beneficial effects. Transcriptomic analysis revealed that differentially expressed genes post-celastrol treatment were associated with steroid biosynthesis, estrogen signaling pathways, type 2 diabetes, insulin secretion, meiosis, and apoptosis. Additionally, insulin receptor substrate 1 (IRS1), an adapter protein in insulin signaling, was shown to advance puberty in young mice and to facilitate oocyte maturation. Overexpression of IRS1 in oocytes promoted follicular development and oocyte maturation, resulting in enhanced steroid hormone levels, whereas IRS1 knockdown inhibited these processes. Our findings indicate that celastrol may regulate ovarian development and aging by modulating IRS1 expression and its related pathways, suggesting celastrol as a novel small-molecule compound targeting IRS1, and offering new perspectives for potential therapeutic strategies against reproductive aging and infertility.

Animals↗

PubMed2026

Hypothalamic-Pituitary Axis Involvement in Primary Central Nervous System Lymphoma.

CONTEXT: Primary central nervous system lymphoma (PCNSL) is a rare malignancy that may involve the hypothalamic-pituitary axis (HPA), leading to underrecognized but clinically significant endocrine dysfunction. OBJECTIVE: This work aims to characterize the spectrum and patterns of HPA-related endocrine disturbances in patients with PCNSL. DATA SOURCES: A systematic search was conducted in PubMed, EMBASE, Scopus, and Web of Science, supplemented by gray literature. The search concluded in February 2025. STUDY SELECTION: We included studies reporting adult PCNSL cases with documented dysfunction of at least one hormonal axis. Exclusion criteria were preexisting hypopituitarism or lack of endocrine data. DATA EXTRACTION: Data on demographics, tumor localization, hormonal axes affected, radiological findings, treatment, and outcomes were extracted. Risk of bias was assessed using JBI tools. RESULTS: Ninety-nine cases met the inclusion criteria. Diffuse large B-cell lymphoma accounted for 84% of cases. Endocrine dysfunction included isolated adenohypophyseal involvement (46%), neurohypophyseal (8%), and combined (45%). The most affected pituitary axes were the gonadal and thyroid axes, with 89.7% and 89.2% involvement, respectively. Hypothalamic tumors were strongly associated with combined dysfunction (odds ratio = 9.47; 95% CI, 3.76-23.86; P < .001). Persistent endocrinopathy was more frequent in progressive disease. No direct association was found between endocrine dysfunction and mortality. CONCLUSION: HPA dysfunction in PCNSL is frequent and often underdiagnosed. Hypothalamic involvement is associated broader hormonal impairment. Routine hormonal screening and multidisciplinary management should be standard in PCNSL care to minimize complications and improve outcomes.

Humans↗

PubMed2026

Screening of Estrogenic and Antiestrogenic Effects of Estradiol, Bisphenol A, and Fulvestrant Using 2D and 3D Breast Cancer Cell Systems With a Luciferase Reporter Gene Assay.

Endocrine-disrupting chemicals (EDCs) like bisphenol A (BPA) pose health risks by interfering with hormones. This study develops and utilizes in vitro 2D and 3D cell models to evaluate the estrogenic and antiestrogenic properties of compounds. Human breast cancer cell lines T47D and MCF7, stably transfected with a luciferase reporter gene (ERE-LUC), were first compared in 2D. Due to the significantly higher sensitivity and responsiveness observed in the T47D line during preliminary 2D screenings, this cell line was exclusively selected for the development of the 3D spheroid model. Cells were treated with 17β-estradiol (E2), BPA, and Fulvestrant (FUL) to assess cell viability and luciferase activity. In 2D models, T47D ERE-LUC cells showed higher responsiveness than MCF7 ERE-LUC, which failed to show significant luciferase induction with E2. In the 3D T47D model, cells exhibited significant and robust changes in luciferase activity in response to E2 and BPA, highlighting the enhanced fidelity of 3D cultures in replicating tissue conditions compared to their 2D counterparts. The study highlights the effectiveness of 3D models over 2D in evaluating estrogenic activity. Specifically, the 3D T47D ERE-LUC system serves as a superior, sensitive, and reliable platform for screening EDCs, offering benefits in cost, data speed, and reduced in vivo reliance.

Humans↗

PubMed2026

Comparative adipokine profile in middle-aged master athletes, untrained adults, and young individuals.

BACKGROUND: Adipose tissue is an active endocrine organ involved in metabolic regulation and systemic inflammation, processes that are altered during aging. Nevertheless, the adipokine profile associated with lifelong physical training in master. athletes remains incompletely characterized. AIM: This study investigated circulating concentrations of adiponectin, leptin, resistin, insulin, and the leptin-to-adiponectin and adiponectin-to-resistin ratios in four male groups: endurance master athletes (ME), master sprinters (MS), untrained middle-aged adults (UMA), and untrained young adults (YU). METHODS: ME (n = 17, 50.5 ± 9.6 years), MS (n = 30, 50.3 ± 6.2 years), UMA (n = 16, 48.5 ± 7.5 years), and YU (n = 23, 23.7 ± 4.0 years) underwent anamnesis, anthropometric assessments, and serum concentrations of adiponectin, leptin, resistin, and insulin using commercial ELISA kits. RESULTS AND DISCUSSION: Significant group differences were observed for all variables (p < 0.001). UMA exhibited higher concentrations of leptin, insulin, and resistin, together with an elevated leptin-to-adiponectin ratio and a reduced adiponectin-to-resistin ratio compared with the other groups (p < 0.05). MS also presented higher leptin and insulin levels and an increased leptin-to-adiponectin ratio compared. with YU (p < 0.05), as well as a lower adiponectin-to-resistin ratio (p < 0.05). Overall, effect sizes were large across outcomes, and master athletes displayed a more favorable adipokine profile than untrained middle-aged adults, suggesting potential metabolic adaptations associated with lifelong training. CONCLUSIONS: Middle-aged master athletes exhibited a more favorable adipokine profile than untrained middle-aged adults, with values approaching those observed in young individuals.

Adipose tissue↗