Molecular and Cellular Endocrinology最新文献

{"title":"FNDC4 regulates M2 polarization of tumor-associated macrophages to affect colorectal cancer metastasis","authors":"Shengyuan Liu ,&nbsp;Feng Huang ,&nbsp;Jianmin Wang ,&nbsp;Jingfeng Liu","doi":"10.1016/j.mce.2026.112738","DOIUrl":"10.1016/j.mce.2026.112738","url":null,"abstract":"<div><div>A very dangerous tumor, colon cancer has the potential to spread and come back. Investigating FNDC4's function in colon cancer and its molecular mechanism is the goal of this study. The expression of FNDC4 and M2 macrophage-related genes (CD163 and CD206) in tumor tissues was found using immunohistochemistry. After transfecting colorectal cancer cells with the FNDC4 knockdown plasmid, CCK8, clone formation, scratch assay, and Transwell test were used to determine cell proliferation, migration, and invasion. Using flow cytometry, the amount of CD163, CD206, and the rate of cell death were found. Western blot was utilized to identify the expression of proteins associated with the Akt/STAT3 pathway, M2 macrophages, and epithelial-mesenchymal cells. To see how sh-FNDC4 affected tumor growth, a xenograft tumor model was created, and H&amp;E staining was used to look at liver tissue metastases. The findings demonstrated that FNDC4 was favorably connected with the expression of CD206 and CD163 and that it was substantially expressed in colorectal cancer. Tumor cell proliferation, migration, invasion, EMT, and M2 macrophage polarization were all reduced by FNDC4 knockdown. Furthermore, FNDC4 knockdown suppressed tumor growth and liver metastasis in vivo by blocking the Akt/STAT3 pathway. In conclusion, FNDC4's modulation of the Akt/STAT3 pathway may be the reason why its knockdown prevented colorectal cancer cell proliferation, metastasis, and M2 macrophage polarization.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"615 ","pages":"Article 112738"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The implementation of small molecule agonists and antagonists to elucidate gonadotropin receptor structure, function and physiology","authors":"James A. Dias ,&nbsp;Claire L. Newton ,&nbsp;Alfredo Ulloa-Aguirre","doi":"10.1016/j.mce.2026.112735","DOIUrl":"10.1016/j.mce.2026.112735","url":null,"abstract":"<div><div>Pursuant to patient desires of alternatives to injectable gonadotropins, a plethora of attempts have identified, characterized, and demonstrated efficacy of small molecules that activate (agonists) gonadotropin receptors. Discoveries have also been made of small molecule gonadotropin receptor inhibitors (antagonists), which have potential as useful alternatives to steroid hormone-based contraception. Implementation of these small molecules in advanced testing systems not necessarily used in screening, which identified lead compounds, has yielded a bounty of wonders. It is likely that a richer understanding of the role of signaling platforms and conformation-dependent molecular assemblies are likely to emerge. Several small molecule agonists have been observed to function as conformational boosters that can rescue receptor trafficking defects, or initiate internalization of receptors without bound hormone. Still others have revealed insights into the role of molecular platforms in persistent signaling. Unexpectedly, such antagonists, like molecular scalpels, can ablate certain signaling pathways and not others leading to discovery of biased signaling in gonadotropin receptors. That seminal observation has led to studies of nuanced signaling and, consequently, nuanced gene expression. Gonadotropin receptor structure-based design for better specificity and potency of agonists and antagonists has been provided by new cryo-EM structures of the gonadotropin receptors, demonstrating proof of concept. Structural determination of downstream supramolecular assemblies will be necessary to validate and fully understand these complicated receptors and how their interaction with other proteins and when occupied by hormone and allosteric modulators, nuances their actions and, ultimately, fertility.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"615 ","pages":"Article 112735"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperglycemia differentially regulates osteoblast and osteoclast autophagy via AMPK/mTOR/p70 S6K signaling in diabetic osteoporosis","authors":"Bin Zhou ,&nbsp;Fen Feng ,&nbsp;Cila Zhou ,&nbsp;Kuang Yao ,&nbsp;Ping Huang","doi":"10.1016/j.mce.2026.112739","DOIUrl":"10.1016/j.mce.2026.112739","url":null,"abstract":"<div><div>Type 2 diabetes mellitus (T2DM) often induces diabetic osteoporosis (DOP) with impaired bone remodeling, yet its underlying mechanism remains elusive. This study identified the differential regulatory role of the AMPK/mTOR/p70 S6K signaling axis in bone cell function. In vivo, diabetes reduced AMPK phosphorylation, enhanced mTOR/p70 S6K activation, and diminished autophagy in rat femoral tissue. In vitro, HG exerted cell-type-specific effects via the AMPK signaling pathway: in osteoblasts, HG inhibited AMPK phosphorylation, activated mTOR/p70 S6K, suppressed autophagy, and impaired mineralization as well as alkaline phosphatase (ALP) activity; conversely, in osteoclasts, HG enhanced autophagy through the inverse regulatory pathway and accelerated osteoclast differentiation and bone resorption. Collectively, these findings illustrate that hyperglycemia disrupts bone homeostasis via cell-type-specific regulation of AMPK, suggesting that AMPK-mediated autophagy serves as a potential critical therapeutic target for diabetes-related bone diseases.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"615 ","pages":"Article 112739"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-Hydroxyestradiol regulates extracellular matrix deposition through estrogen receptor beta activation in airway smooth muscle cells","authors":"Ashish Kumar ,&nbsp;Mohammad Irshad Reza ,&nbsp;Anurag Banerjee ,&nbsp;Nilesh Sudhakar Ambhore ,&nbsp;Premanand Balraj ,&nbsp;Buddhadev Layek ,&nbsp;Michael A. Thompson ,&nbsp;John R. Hawse ,&nbsp;Christina M. Pabelick ,&nbsp;Y.S. Prakash ,&nbsp;Venkatachalem Sathish","doi":"10.1016/j.mce.2026.112753","DOIUrl":"10.1016/j.mce.2026.112753","url":null,"abstract":"<div><div>Airway remodeling in asthma is characterized by increased extracellular matrix (ECM) production and deposition by airway smooth muscle (ASM) cells. Existing studies have shown contrasting effects of 17β-estradiol (E₂) in regulating ASM cellular remodeling via differential activation of estrogen receptors (ERs: α and β). Even though downstream metabolites of E₂ (2-hydroxyestradiol: 2-HE and 16-hydroxyestradiol: 16αHE₂) are gaining recognition for their biological roles in various cellular systems, their role in ASM remodeling remains largely unexplored. Here, we explore the effects of 2-HE and 16αHE₂, a highly potent metabolites, on ECM remodeling in ASM. ECM mRNA's/proteins expression and deposition were determined by Western blotting, qRT-PCR, and In-Cell Western analysis. Interaction of metabolites with ERs was performed using a docking study and their impact on regulation of an estrogen response element (ERE) was monitored via a luciferase reporter assay. Further, the ER-specific effect of metabolites was validated using shRNA-mediated ERα and ERβ knockdown ASM cells. 16αHE₂ exposure showed no notable changes in transforming growth factor-β (TGF-β)-induced ECM proteins expression and deposition, whereas 2-HE exposure blunted the TGF-β effects. Molecular docking unveiled the binding of 16αHE₂ with ERα, while 2-HE more strongly bound to ERβ, which was also confirmed by ERE-luciferase assay. In ERβ knockdown ASM cells, 2-HE inhibited the TGF-β-induced phosphorylation of SMAD2/3, AKT, and ERK1/2. However, 16αHE₂ failed to elicit any of these effects. Furthermore, 2-HE significantly decreased the TGF-β-induced transcriptional activities of AP-1 and NF-κB. Overall, our findings suggest 2-HE blunts TGF-β-induced ECM through ERβ; therefore, it may serve as a novel therapeutic target for airway remodeling and asthma.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"615 ","pages":"Article 112753"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolite profiling of the effect of prenatal stimuli across postnatal treatments in the liver","authors":"Bruce R. Southey ,&nbsp;Andrea N. Gomez ,&nbsp;Gloria R. Sunderland ,&nbsp;Chance W. Riggins ,&nbsp;Maria B. Villamil ,&nbsp;Sandra L. Rodriguez-Zas","doi":"10.1016/j.mce.2026.112744","DOIUrl":"10.1016/j.mce.2026.112744","url":null,"abstract":"<div><div>Hepatic molecular mechanisms can be modulated by pro- and anti-inflammatory signals associated with infections and nutritional changes that can, in turn, affect the endocrine system. The sex-specific interplay between stimuli on hepatic pathways was studied using a biomedical model. The liver metabolome of pigs exposed to a prenatal immune activation from maternal infection was compared to that of matching female and male controls. Within prenatal treatment and sex group, the postnatal treatments were synthetic inflammatory factor, feeding deprivation (fasting), or saline. Liquid chromatography mass spectrometry enabled the detection of 2554 metabolites with significant (False Discovery Rate-adjusted p-value &lt;0.05) sex, prenatal, and postnatal treatment effects. The glycine, serine, and threonine metabolism, RNA metabolism, and neurotransmitter transporters pathways included metabolites with prenatal-by-postnatal treatment interaction effects, such as alanine, arginine, and ketobutyric acid. These disruptions can impact hepatic detoxification, protein synthesis, and methylation. The synergistic interaction for adenosylhomocysteine was characterized by higher levels in the postnatal fasted relative to the saline-treated group, whereas this trend was 4.5-fold higher in the prenatal immune-activated group compared to controls. The antagonistic interaction for chenodeoxycholyltaurine was characterized by higher levels in prenatal-activated relative to controls under saline conditions, whereas this trend declined 2.2-fold in the postnatal-stimulated groups. Sex-specific effects were observed for glutamic acid, with differences between prenatal groups 4.7 times higher in males than in females. These findings offer insights into the interplay between sex, prenatal, and postnatal stimuli across pathways that must be considered in the development of therapies to optimize liver function.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"615 ","pages":"Article 112744"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma proteome mendelian randomization and network pharmacology reveal therapeutic targets for thyroid disorders","authors":"Chao Wang ,&nbsp;Yi Cai ,&nbsp;Xing Yang,&nbsp;Jie Jie","doi":"10.1016/j.mce.2026.112752","DOIUrl":"10.1016/j.mce.2026.112752","url":null,"abstract":"<div><h3>Introduction</h3><div>Thyroid disorders, including hypothyroidism, hyperthyroidism, and thyroid cancer, impose a substantial global health burden. Existing treatments face limitations due to adverse effects and incomplete efficacy, highlighting the need for innovative therapeutic strategies informed by genetic and molecular insights.</div></div><div><h3>Methods</h3><div>We integrated Mendelian randomization (MR) with network pharmacology to systematically prioritize druggable targets. Genetic correlations between different thyroid disorders were evaluated using linkage disequilibrium score regression analysis. Plasma protein quantitative trait loci from 4907 plasma proteins were leveraged as instrumental variables in MR analyses across two independent cohorts. Bayesian colocalization validated shared causal variants. Network pharmacology methods encompassed constructing protein-protein interaction networks, conducting functional enrichment analyses, and identifying potential therapeutic compounds via the DSigDB database. Docking and dynamics simulations assessed binding and stability, while PheWAS assessed off-target effects.</div></div><div><h3>Results</h3><div>The LDSC analysis identified notable genetic correlations of hypothyroidism with hyperthyroidism (Rg = 0.167, P = 0.017), as well as hyperthyroidism with thyroid cancer (Rg = 0.286, P = 0.033). MR and colocalization identified seven causal proteins: IL2RB, CDH1, FGF19 (hypothyroidism); PSAPL1 (hyperthyroidism); DCP1B, SPRN, RPS6KA6 (thyroid cancer). Drug prediction prioritized compounds such as BI-2536 (binding energy: −9.5 kcal/mol with RPS6KA6) and deoxycholic acid. PheWAS confirmed minimal pleiotropic risks.</div></div><div><h3>Conclusions</h3><div>By synergizing genetic epidemiology with network pharmacology, this study delineates shared genetic architecture among thyroid disorders and nominates seven high-confidence targets with therapeutic potential. The integrative framework advances precision medicine by bridging causal plasma protein identification, mechanistic pathway mapping, and drug repurposing, offering a blueprint for multi-omics-driven drug discovery in endocrine pathologies.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"615 ","pages":"Article 112752"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etomidate relieves oxaliplatin-induced neuropathic pain by regulating AMPK/Nrf2/HO-1 axis.","authors":"Kexin Chen, Yuchao Lin, Xuechang Han, Lei Zhao, Jing Wang, Yu Li","doi":"10.1016/j.mce.2026.112791","DOIUrl":"https://doi.org/10.1016/j.mce.2026.112791","url":null,"abstract":"<p><strong>Background: </strong>Etomidate (Eto) is widely employed in clinical anesthesia induction. Whereas, the function of Eto in neuropathic pain caused by anticancer chemotherapeutic drug remains indistinct. Hereof, the research attempted to unveil the regulatory mechanisms of Eto in oxaliplatin (OXA) elicited neuropathic pain.</p><p><strong>Material and methods: </strong>The mice model was established by OXA induction and administrated by Eto along with the concentrations of 1.5, 3 and 6 mg/kg. The nociceptive behaviors such as paw withdrawal threshold (PWT), flinches, paw withdrawal latency (PWL) and latency were analyzed. By executing HE staining, RT-qPCR, western blot and the corresponding kits, the influences of Eto in inflammatory response and oxidative stress response in OXA model were explored. AMPK/Nrf2/HO-1 pathways were studied to uncover the potential mechanism. After creation of C6 cells model, the effects of Eto in neuropathic pain were further investigated in vitro.</p><p><strong>Results: </strong>Eto significantly relieved OXA-irritated nociceptive behaviors via elevating the values of PWT and PWL, declining the number of spontaneous flinches, meanwhile restoring latency to fall. Moreover, Eto triggered a robust anti-inflammatory response, which lowered inflammatory scores and suppressed GFAP, IL-1β, TNF-α and NLRP3 expression. Additionally, Eto obviously enhanced SOD and GSH levels, but reduced MDA and COX2 levels, thereby mitigating OXA-induced oxidative stress response. Mechanism study discovered that activation of AMPK/Nrf2/HO-1 pathways participated in regulating the neuroprotective function of Eto in inflammatory response and oxidative stress response in OXA-treated mice and in C6 cells model.</p><p><strong>Conclusions: </strong>The research announced that Eto improved OXA-induced neuropathic pain by regulating AMPK/Nrf2/HO-1 pathway.</p>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112791"},"PeriodicalIF":3.6,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “The local corticotropin-releasing hormone receptor 2 signalling pathway partly mediates hypoxia-induced increases in lipolysis via the cAMP–protein kinase A signalling pathway in white adipose tissue” [Mol. Cellul. Endocrinol. 392/1–2 (2014) 106–114]","authors":"Yanlei Xiong ,&nbsp;Zhuan Qu ,&nbsp;Nan Chen ,&nbsp;Hui Gong ,&nbsp;Mintao Song ,&nbsp;Xuequn Chen ,&nbsp;Jizeng Du ,&nbsp;Chengli Xu","doi":"10.1016/j.mce.2025.112680","DOIUrl":"10.1016/j.mce.2025.112680","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"614 ","pages":"Article 112680"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circPTPRM can encode a functional polypeptide circPTPRM-187aa to promote papillary thyroid carcinoma progression","authors":"Chengzhou Lv,&nbsp;Jiapeng Huang,&nbsp;Xiaoyu Ji,&nbsp;Wei Sun,&nbsp;Hao Zhang","doi":"10.1016/j.mce.2026.112734","DOIUrl":"10.1016/j.mce.2026.112734","url":null,"abstract":"<div><h3>Aims</h3><div>Papillary thyroid carcinoma (PTC) is the most common thyroid tumor, usually with a good prognosis, though some cases show early invasion, metastasis, and may become iodine-refractory. circRNAs can interact with miRNAs, bind proteins, regulate transcription, and encode polypeptides, but their translation function in thyroid cancer remains unexplored.</div></div><div><h3>Methods</h3><div>Quantitative real-time PCR (qRT-PCR), agarose gel electrophoresis, circRNA stability assessment, fluorescence in situ hybridization (FISH) were performed to explore the expression profile of circPTPRM in PTC tissues and adjacent non-cancerous thyroid tissues. We performed molecular biological and cell function experiments by constructing knockdown and various overexpression vectors. Effects of circPTPRM on PTC tumorigenesis were investigated through in vitro and in vivo experiments. The mechanism of circPTPRM-mediated tumor promotion was explored through immunofluorescence (IF), LC-MS/MS, immunoprecipitation (IP) and Co-immunoprecipitation (Co-IP), protein stability assessment, and ubiquitination assay.</div></div><div><h3>Results</h3><div>We confirmed that circPTPRM influenced PTC cell proliferation, migration, invasion through its translated polypeptides. In vivo experiments with nude mouse tumors also demonstrated that overexpression of circPTPRM contributed to the tumor's increased volume and weight. Subsequently, in the mechanistic analysis we found that circPTPRM-187aa polypeptide could bind IQGAP1 and induce TGF-β pathway activation by elevating RAC1 and CDC42.</div></div><div><h3>Conclusion</h3><div>CircPTPRM can encode circPTPRM-187aa polypeptide. circPTPRM-187aa, regulates the expression of IQGAP1 protein, and up-regulates RAC1 and CDC42 proteins in TGF-β signaling pathway, enhancing the PTC cells proliferation, migration, and invasion.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"614 ","pages":"Article 112734"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental exposure to a mixture of propiconazole and glyphosate induces histopathological lesions in the prostate of postpubertal rats","authors":"Ayelen L. Gomez ,&nbsp;Débora G. Reato ,&nbsp;Eduardo Masat ,&nbsp;Laura Kass ,&nbsp;Gabriela A. Altamirano","doi":"10.1016/j.mce.2026.112730","DOIUrl":"10.1016/j.mce.2026.112730","url":null,"abstract":"<div><div>Pesticide mixture exposure during critical developmental windows is a growing public health concern, given their potential additive or synergistic effects on the male reproductive system. This study aimed to evaluate whether developmental exposure to a mixture of propiconazole (PRO) and glyphosate (GLY) alters the postpubertal rat prostate. Pregnant rats were orally exposed to vehicle (saline) or a mixture of PRO and GLY (4 mg PRO/kg/day and 3.7 mg GLY/kg/day) from gestation day 9 until weaning. On postnatal day 60, male offspring were euthanized, and the prostate and serum samples were collected. PROGLY-exposed rats exhibited changes in the ventral and dorsolateral prostate histoarchitecture, including epithelial and stromal remodeling and increased incidence of prostate lesions. In the ventral prostate, although the relative glandular area remained unchanged, PROGLY exposure exhibited increased epithelial height and decreased luminal acinar area. Also, hyperplastic and atrophic acini were more prevalent in these animals. PROGLY exposure reduced estrogen receptor beta (ESR2) protein level, particularly in hyperplastic and atrophic acini, without affecting androgen or estrogen receptor alpha. ESR2 decrease was associated with an increased cell proliferation index in hyperplastic acini and a reduction in serum testosterone level in PROGLY-exposed rats. Stromal alterations included increased smooth muscle cell layers and reduced vimentin-positive fibroblasts, with no evidence of myofibroblast presence. This study shows that developmental exposure to PROGLY disrupts normal ventral prostate architecture and hormone signaling in postpubertal rats. These findings highlight the potential long-term risks of combined pesticide exposure on male reproductive health and the importance of evaluating mixture effects.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"614 ","pages":"Article 112730"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}