Ryhem Gam, Kevin Sochodolsky, Aurélio Balsalobre, Yves Gauthier, Jacques Drouin
{"title":"EGF activation of POMC gene transcription is mediated by STAT3.","authors":"Ryhem Gam, Kevin Sochodolsky, Aurélio Balsalobre, Yves Gauthier, Jacques Drouin","doi":"10.1530/JME-25-0037","DOIUrl":"10.1530/JME-25-0037","url":null,"abstract":"<p><p>Classical activation of the hypothalamic-pituitary-adrenal axis is exerted by the stimulation of pituitary POMC gene transcription and ACTH release by the hypothalamic hormone CRH. In parallel, inflammatory cytokines such as IL6 and LIF also stimulate ACTH release and POMC transcription through the JAK/STAT pathway. In recent years, a particular interest in the role of the EGF pathway for POMC activation was sparked by the identification of causative mutations in the USP8 gene that have been implicated in the formation of pituitary corticotroph adenomas that are the hallmark of Cushing's disease. These mutations were associated with the persistent upregulation of the EGF/EGFR pathway and its putative role in ACTH hypersecretion. In the present work, we reassessed the signaling pathways that are activated in response to EGF in pituitary corticotroph cells using the AtT20 cell model. We confirmed the activation of the MAP kinase pathway by EGF and also showed the activation of the AKT/mTOR and JAK/STAT pathways. Whereas activation of all three pathways appears essential for the stimulation of cell proliferation, only the JAK/STAT pathway, and more specifically STAT3, enhances POMC gene transcription. This action is mapped to a single STAT-binding element of the POMC promoter in contrast to the activation by the other STAT-activating cytokines LIF and IL6. Furthermore, EGF signaling is specifically enhanced by STAT3 but not STAT1 in contrast to LIF-dependent activation. All together, the data identified a unique STAT3-dependent target on the POMC promoter that mediates EGF activation of POMC gene transcription.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591480","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":"Mechanistic insights of Rhodiola crenulata in treating diabetic kidney disease via network pharmacology.","authors":"Junhan Li, Yuying Cui, Jinming Yao, Congcong Guo, Mingwen Jiao","doi":"10.1530/JME-25-0006","DOIUrl":"10.1530/JME-25-0006","url":null,"abstract":"<p><p>Rhodiola crenulata (RC) has been traditionally used for its therapeutic benefits, including alleviating high-altitude sickness, fatigue, and diabetes. Diabetic kidney disease (DKD), a severe complication of diabetes, often leads to progressive renal fibrosis. This study explored the protective effects of RC against kidney fibrosis in DKD rat models, identifying active compounds and their therapeutic targets, with a focus on salidroside (SAL), a key component of RC. After administering RC to DKD rats, network pharmacology analysis identified 22 core components and 141 DKD-related therapeutic targets, with TGFB1 emerging as a primary target in kidney fibrosis. In vivo experiments demonstrated that RC reduced fibrosis markers by decreasing glomerular mesangial expansion, collagen deposition, and myofibroblast proliferation, alongside lowering TGF-β1 levels. In vitro analyses revealed that SAL inhibited high glucose-induced fibroblast activation and suppressed TGF-β1 expression in proximal renal tubular epithelial cells (PTECs), suggesting its direct role in slowing fibrosis progression. These findings indicate that the antifibrotic effects of RC in DKD may be attributed to SAL's ability to regulate fibroblast activity and suppress TGF-β1, highlighting its potential as a therapeutic component for DKD management.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285032","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}
Yue Wang, Minah Kim, Chantal Buckley, Stephen M F Jamieson, Jo K Perry
{"title":"Combination of growth hormone receptor antagonist and radiation reduces tumour growth in a lung cancer xenograft model.","authors":"Yue Wang, Minah Kim, Chantal Buckley, Stephen M F Jamieson, Jo K Perry","doi":"10.1530/JME-25-0007","DOIUrl":"10.1530/JME-25-0007","url":null,"abstract":"<p><p>Lung cancer is the primary cause of cancer-related deaths worldwide. A substantial proportion of patients will undergo radiotherapy during treatment. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis has been implicated in cancer progression and resistance to radiation therapy. Elevated GH receptor (GHR) mRNA expression is observed in tumour tissue from non-smoking female patients with non-small cell lung cancer (NSCLC) and a genetic variant in the GHR is associated with increased lung cancer risk. Here, we evaluate the efficacy of a GHR antagonist (GHA2) in combination with radiation therapy in a NSCLC xenograft model. NCI-H460 xenografts grown in immunodeficient NIH-III mice were treated with PEGylated GHA2 (GHA2-PEG) (30 mg/kg/day) ± fractionated gamma radiation (10 × 2.5 Gy over 5 days). IGF-1 concentrations were reduced by 56-59% in GHA2-PEG-treated groups compared to vehicle-treated controls. Treatment with GHA2-PEG significantly increased the median time tumours took to reach 4× the pre-radiation treatment volume when compared to radiation alone (28 versus 23 days; P < 0.05). Immunohistochemical analysis demonstrated that treatment with GHA2-PEG decreased the area of CD31 labelling in irradiated tumours, suggesting an anti-vascular effect, but this was not observed in non-irradiated tumours. Moreover, administering GHA2-PEG significantly reduced the area of CD11b labelling in non-irradiated tumours, and reduced pimonidazole staining in irradiated tumours, indicating that GHR antagonism reduced tumour angiogenesis and hypoxic regions. Our results suggest that GHA2-PEG treatment sensitises NSCLC cell NCI-H460 to radiation and may improve the response of GH- and/or IGF1-responsive lung tumours to radiotherapy.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064044","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":"Kisspeptin isoforms: versatile players in reproduction and beyond.","authors":"Aishwarya P Chakraborty, Antara A Banerjee","doi":"10.1530/JME-25-0001","DOIUrl":"10.1530/JME-25-0001","url":null,"abstract":"<p><p>Kisspeptin and its cognate G-protein-coupled receptor (GPCR), the kisspeptin-1 receptor (KISS-1R), are central to mammalian reproduction, regulating the hypothalamic-pituitary-gonadal axis. They are upstream regulators of gonadotropin-releasing hormone (GnRH) secretion, a hallmark of the onset of puberty, subsequently tuning luteinizing hormone and follicle-stimulating hormone levels and bringing about steroid hormone production. In mammals, kisspeptin (Kp) is synthesized as a 145-mer pre-pro-polypeptide by the KISS1 gene, which further undergoes cleavage to form four kisspeptin isoforms: Kp-54, Kp-14, Kp-13 and Kp-10. They all share a common decapeptide sequence (Kp-10), followed by an RF-amide in their C-terminal end. Kp-10, the smallest isoform, is reported to activate KISS-1R to its full functional potential. The reproductive roles of Kp-54 and Kp-10 have been studied extensively by in vivo and clinical studies owing to their longer terminal half-life and commercial bargain, respectively. This comprehensive review aims to collate the multitude of functions displayed by all naturally occurring kisspeptin isoforms and other kisspeptin-like peptides in reproduction and beyond, including metabolic regulation and therapeutic potential. The structural architecture of kisspeptin isoforms reported using alanine scan substitution studies and secondary structure using circular dichroism and nuclear magnetic resonance spectroscopy studies have also been highlighted. Several kisspeptin agonists and antagonists have been developed for ovulation induction in assisted reproduction and management of pubertal disorders. This review summarizes the diverse roles and structural insights of kisspeptin isoforms to help in the identification of new horizons and thematic areas for basic and translational research, culminating in potential therapeutic applications.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009472","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}
Ciaran A Shaughnessy, Valorie D Myhre, Stephen D McCormick, Robert M Dores
{"title":"Functionally divergent melanocortin receptor subtypes and the HPI axis in sea lamprey.","authors":"Ciaran A Shaughnessy, Valorie D Myhre, Stephen D McCormick, Robert M Dores","doi":"10.1530/JME-24-0126","DOIUrl":"10.1530/JME-24-0126","url":null,"abstract":"<p><p>The hypothalamus-pituitary-interrenal (HPI) axis is a highly conserved neuroendocrine system in vertebrates, but many details of its physiological role in jawless vertebrates remain unclear. Unlike the proopiomelanocortin (Pomc) gene of jawed vertebrates, lampreys have two divergent melanocortin prohormones, a proopiocortin (Poc) encoding adrenocorticotropic hormone (Acth) and promelanotropin (Pom) encoding two melanocyte-stimulate hormones (Msh-a and Msh-b). This study investigated the HPI axis in sea lamprey (Petromyzon marinus) by characterizing the potential involvement of key HPI components through gene expression analyses and functional studies. Phylogenetic analysis revealed that the two lamprey melanocortin receptors, Mcar and Mcbr, occupy basal positions relative to gnathostome melanocortin receptors. We observed that tissue-specific transcriptional patterns of HPI axis genes, including mcar and steroidogenic acute regulatory protein (star), are both expressed in a 'head kidney' region, suggesting a concomitant role in a corticosteroidogenic HPI axis. Both Mcar and Mcbr receptors can be activated by lamprey Acth, Msh-a and Msh-b peptides. Notably, Mcar was more potently activated by Msh peptides over Acth, and neither receptor required the melanocortin receptor accessory protein (Mrap), which is required for gnathostome Mc2r function. These findings indicate that the strong selectivity for Acth and Mrap1-dependence of Mc2r may be derived traits that evolved after the agnathan-gnathostome divergence. Our results provide evidence for a functional HPI axis in lamprey, albeit with unique features compared to gnathostomes. This study offers insights into the evolutionary origins of the vertebrate HPI axis and highlights the need for further investigation into the regulation and physiological roles of the agnathan HPI axis.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009357","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}
Maria-Nefeli Malliou-Becher, Eva-Maria Turnwald, Lara Skupin, Tobias Kretschmer, Andrea Mesaros, Martin Purrio, Maria Wohlfarth, Marion Handwerk, Simone Kalis, Dirk Gründemann, Jörg Dötsch, Ariane Germeyer, Sarah Appel
{"title":"Effect of metformin on the endometrial proteome of diet-induced obese mice.","authors":"Maria-Nefeli Malliou-Becher, Eva-Maria Turnwald, Lara Skupin, Tobias Kretschmer, Andrea Mesaros, Martin Purrio, Maria Wohlfarth, Marion Handwerk, Simone Kalis, Dirk Gründemann, Jörg Dötsch, Ariane Germeyer, Sarah Appel","doi":"10.1530/JME-24-0098","DOIUrl":"10.1530/JME-24-0098","url":null,"abstract":"<p><p>Obesity is known to have detrimental effects on female fertility, influencing both ovarian and endometrial functions. There is evidence that endometrial function is altered in obese and/or insulin-resistant women. Metformin, an insulin-sensitizing drug, has shown potential in treating metabolic and reproductive disorders, including polycystic ovary syndrome (PCOS) and may enhance fertility outcomes by improving endometrial dysfunction. Using a mouse model, this study aimed to investigate how a high-fat diet impacts endometrial-specific protein expression and whether metformin can mitigate these effects. C57BL/6N mice were fed a standard or high-fat diet and either received metformin treatment or did not. Proteomic analyses revealed significant alterations in endometrial protein expression due to the high-fat diet, while metformin administration appeared to restore many of these changes to normal levels. Metformin's impact was evident through alterations in specific proteins associated with reproductive health and metabolic functions, such calcium-independent phospholipase A2-gamma, ATP-binding cassette sub-family D member 1, RAC-beta serine/threonine-protein kinase, acyl-CoA:lysophosphatidylglycerol acyltransferase 1, O-GlcNAcase, scavenger receptor class A member 3, protein kinase C beta type, sortilin, beta-2-microglobulin and apolipoprotein C-III. These results suggest a potential therapeutic role for metformin in normalizing endometrial protein expression, providing insights into how this drug could improve fertility outcomes in obese or insulin-resistant females, besides normalizing ovulation patterns. Overall, this study enhances our understanding of the relationship among obesity, endometrial function and metformin's therapeutic potential, offering a foundation for further research into reproductive health and metabolic disorders.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"74 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014944","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}
Maria L Price, Rachael A Wyatt, Joao Correia, Zakia Areej, Maisie Hinds, Ana Crastin, Rowan S Hardy, Morten Frost, Caroline M Gorvin
{"title":"Identification of anti-resorptive GPCRs by high-content imaging in human osteoclasts.","authors":"Maria L Price, Rachael A Wyatt, Joao Correia, Zakia Areej, Maisie Hinds, Ana Crastin, Rowan S Hardy, Morten Frost, Caroline M Gorvin","doi":"10.1530/JME-24-0143","DOIUrl":"10.1530/JME-24-0143","url":null,"abstract":"<p><p>Osteoporosis diagnoses are increasing in the ageing population, and although some treatments exist, these have several disadvantages, highlighting the need to identify new drug targets. G protein-coupled receptors (GPCRs) are transmembrane proteins whose surface expression and extracellular activation make them desirable drug targets. Our previous studies have identified 144 GPCR genes to be expressed in primary human osteoclasts, which could provide novel drug targets. The development of high-throughput assays to assess osteoclast activity would improve the efficiency at which we could assess the effect of GPCR activation on human bone cells and could be utilised for future compound screening. Here, we assessed the utility of a high-content imaging (HCI) assay that measured cytoplasmic-to-nuclear translocation of the nuclear factor of activated T cells-1 (NFATc1), a transcription factor that is essential for osteoclast differentiation, and resorptive activity. We first demonstrated that the HCI assay detected changes in NFATc1 nuclear translocation in human primary osteoclasts using GIPR as a positive control, and then developed an automated analysis platform to assess NFATc1 in nuclei in an efficient and unbiased manner. We assessed six GPCRs simultaneously and identified four receptors (FFAR2, FFAR4, FPR1 and GPR35) that reduced osteoclast activity. Bone resorption assays and measurements of TRAP activity verified that activation of these GPCRs reduced osteoclast activity, and that receptor-specific antagonists prevented these effects. These studies demonstrate that HCI of NFATc1 can accurately assess osteoclast activity in human cells, reducing observer bias and increasing efficiency of target detection for future osteoclast-targeted osteoporosis therapies.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"74 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997181","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":"Lack of maternal exposure to somatostatin leads to diet-induced insulin and leptin resistance in mouse male offspring.","authors":"Zhongyue Yang, Catherine P Kirschke, Liping Huang","doi":"10.1530/JME-24-0102","DOIUrl":"10.1530/JME-24-0102","url":null,"abstract":"<p><p>Somatostatin (Sst) is an inhibitory regulator of many hormones. The prenatal environment impacts an offspring's risk to type 2 diabetes in adulthood. However, the effect of maternal Sst deficiency on glucose and insulin metabolism in offspring and metabolic disease risk in their adult life has been poorly understood. The study was to investigate the impact of a lack of maternal Sst exposure in mouse male and female offspring on diet-induced changes in glucose metabolism and adiposity. Sst knockout offspring, SstKO born to the Sst-heterozygous dams or SstKO-MSD born to the Sst-homozygous dams were fed either a regular diet (CD) or a high-fat diet (HFD) at 3-week-old for 15 weeks. Body weight and blood glucose levels were monitored. Glucose and insulin tolerance tests were performed. Plasma hormone levels and gene expression in the hypothalamus were investigated. The results demonstrated that only male SstKO-MSD offspring developed obesity accompanied by severe insulin and leptin resistance after HFD challenge. Insulin secretion was reduced in both basal and oral glucose-challenged conditions in the CD-fed male SstKO-MSD mice. A reduced ratio of islet area to pancreas area was noted in SstKO-MSD mice in both sexes. Plasma levels of glucagon, Glp1 and Pyy were elevated in both male and female SstKO and SstKO-MSD mice. mRNA expression of leptin receptor, FoxO1, Npy and Agrp was downregulated in male SstKO-MSD mice. These results demonstrate that a lack of fetal somatostatin exposure impairs the islet development in offspring and increases risk of obesity, insulin resistance and leptin resistance later in life.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604981","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}
Jinrong Fu, Rili Gao, Qiting Ye, Wenwen Feng, He Liu, Yushu Li, Haixia Guan
{"title":"Disruption of thyroid-intrinsic clock aggravates experimental autoimmune thyroiditis.","authors":"Jinrong Fu, Rili Gao, Qiting Ye, Wenwen Feng, He Liu, Yushu Li, Haixia Guan","doi":"10.1530/JME-25-0022","DOIUrl":"10.1530/JME-25-0022","url":null,"abstract":"<p><p>The core clock gene Bmal1 has been associated with the development of a variety of inflammatory diseases, with its deletion shown to induce or aggravate autoimmune disease in a tissue-specific pattern. Building on our previous findings that light shift can disrupt thyroid clock and exacerbate autoimmune thyroiditis (AIT), we investigated the specific role of the thyroid clock in AIT using a thyrocyte-specific Bmal1 knockdown mouse model (cKO). Our study revealed that Bmal1 knockdown in thyrocytes disrupted the rhythmic expression of intrathyroidal clock genes. Both cKO and Ctrl mice exhibited more severe experimental autoimmune thyroiditis (EAT) when immunized at ZT6 compared to ZT18. However, cKO-EAT mice showed elevated levels of anti-thyroglobulin antibodies (TgAb) and inflammatory cytokines compared to Ctrl-EAT mice, which correlated with CD4+ T cell-mediated immune responses. These findings highlight a novel role for Bmal1 in regulating the thyroid clock and modulating the severity of EAT, uncovering a previously unrecognized connection between circadian regulation and thyroid autoimmune disease.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492436","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}
Lucia Mráziková, Silvie Hojná, Anna Shánělová, Blanka Železná, Jaroslav Kuneš, Lenka Maletínská
{"title":"Anti-inflammatory effects of palm11-PrRP31 in a rat model of lipopolysaccharide-induced acute inflammation.","authors":"Lucia Mráziková, Silvie Hojná, Anna Shánělová, Blanka Železná, Jaroslav Kuneš, Lenka Maletínská","doi":"10.1530/JME-24-0090","DOIUrl":"10.1530/JME-24-0090","url":null,"abstract":"<p><p>Lipopolysaccharides (LPS) are major components of gram-negative bacteria. LPS not only induce endotoxemia and inflammation but also contribute to various diseases. In experimental settings, LPS administration serves as a model for acute inflammatory responses. This study aimed to evaluate the anti-inflammatory potential and mechanism of action of palmitoylated prolactin-releasing peptide (palm11-PrRP31) in a rat model of LPS-induced inflammation. Palm11-PrRP31 has demonstrated efficacy in mitigating LPS-induced weight loss and anorexia, emphasizing its potential protective effects. The cytokine profiles revealed a consistent reduction in tumor necrosis factor α, highlighting the potent anti-inflammatory effects of palm11-PrRP31. The peptide also modulated key cytokines and chemokines in the plasma, liver and hypothalamus, reflecting its broad-spectrum anti-inflammatory properties. Palm11-PrRP31 also effectively attenuated the expression levels of Toll-like receptor 4 signaling components in the liver, suggesting its ability to suppress the activation of these pathways during LPS-induced inflammation. These anti-inflammatory effects were specific to palm11-PrRP31, whereas natural PrRP31 had a minimal impact. In conclusion, this study reveals the efficacy of palm11-PrRP31 in modulating LPS-induced inflammation, offering insights into its immunomodulatory properties. The ability of the peptide to suppress proinflammatory responses and attenuate relevant signaling pathways indicates its potential use as a therapeutic agent for inflammatory disorders.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052745","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}