Endocrinology最新文献

{"title":"Impaired Mitochondrial Biogenesis Inhibits Epithelial-Mesenchymal Transition in Villi of PCOS Patients.","authors":"Hui-Ying Jie, Lu Luo, Bing Cai, Yan Xu, Yuan Yuan, Yang-Xing Wen, Si-Min Liu, Ji-Fan Tan, Ming-Hui Chen, Can-Quan Zhou, Qing-Yun Mai","doi":"10.1210/endocr/bqaf076","DOIUrl":"https://doi.org/10.1210/endocr/bqaf076","url":null,"abstract":"<p><strong>Context: </strong>Polycystic ovary syndrome (PCOS) is accompanied by impaired mitochondrial biogenesis in the ovary and uterus. Whether impaired mitochondrial biogenesis exhibits in villi of PCOS, and its effect and underlying mechanism remain unclear.</p><p><strong>Objective: </strong>This work aimed to investigate mitochondrial biogenesis status and effect on villi of PCOS patients.</p><p><strong>Methods: </strong>Placenta RNA-sequencing data of PCOS downloaded from the GEO database was analyzed with Gene Set Enrichment Analysis (GSEA). GSEA results were validated in first-trimester villi of 8 PCOS patients with euploid miscarriage and 22 matched controls. The function and impact of mitochondrial biogenesis on trophoblast cells were investigated using human trophoblast cell lines HTR-8/SVneo and BeWo.</p><p><strong>Results: </strong>Mitochondria-related and epithelial-mesenchymal transition (EMT) pathways were enriched in placentas of PCOS. In villi of PCOS patients with euploid miscarriage, reduced mitochondrial DNA copy number (mtDNA CN) and N-cadherin protein level, and an elevated E-cadherin protein level were detected, indicating mitochondrial biogenesis dysfunction and impaired EMT. 5 α-Dihydrotestosterone (DHT) exposure downregulated mtDNA CN via reducing mitochondrial transcription factor A (TFAM) level, a critical transcription factor of mtDNA, in HTR-8/SVneo cells. Decreased expression level of TFAM was observed in villi of PCOS. Knockdown of TFAM significantly impeded EMT, characterized by decreased levels of N-cadherin and vimentin in HTR-8/SVneo cells, and increased level of E-cadherin in BeWo cells. Reduction of reactive oxygen species (ROS) mitigated TFAM knockdown-induced impairment of EMT via increasing nuclear Yes-associated protein level in trophoblast cells.</p><p><strong>Conclusion: </strong>The villi of PCOS patients with euploid miscarriage exhibited impaired mitochondrial biogenesis. Androgen-induced downregulation of TFAM impeded EMT via ROS/YAP axis in trophoblast cell.</p>","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":"166 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964447","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":"Comment on \"Atlas of Fshr Expression From Novel Reporter Mice\".","authors":"Livio Casarini, Nafis Rahman, Eric Reiter, Pascale Crépieux, Adolfo Rivero-Müller, Kim C Jonas, T Rajendra Kumar, Alfredo Ulloa-Aguirre, Stephen Franks, Daniel J Bernard, Stine Gry Kristensen, John S Davis, George R Bousfield, James A Dias, Claus Y Andersen, David J Handelsman, Ilpo T Huhtaniemi, Manuela Simoni","doi":"10.1210/endocr/bqaf066","DOIUrl":"10.1210/endocr/bqaf066","url":null,"abstract":"","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779233","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":"GH-Releasing Hormone Neurons Regulate the Hypothalamic-Pituitary-Somatotropic Axis via Short-Loop Negative Feedback.","authors":"Daniela O Gusmao, Maria E de Sousa, Ligia M M de Sousa, Josiane N Silva, Renata Frazao, Edward O List, John J Kopchick, Jose Donato","doi":"10.1210/endocr/bqaf062","DOIUrl":"10.1210/endocr/bqaf062","url":null,"abstract":"<p><p>Growth hormone (GH)-releasing hormone (GHRH) neurons are master regulators of GH secretion. However, the role of these cells in controlling pituitary GH secretion through short-loop negative feedback has not yet been fully clarified. Thus, GHRH-specific GH receptor (GHR) knockout (GHRHΔGHR) mice were generated, and possible consequences on GH secretion and body growth were determined. Approximately 60% of arcuate nucleus GHRH neurons exhibited GH-induced STAT5 phosphorylation, a marker of GHR-expressing cells. This response was practically eliminated in GHRHΔGHR mice. GHR ablation in GHRH-expressing cells increased body weight, lean mass, and naso-anal length in male and female mice without affecting fat mass. The higher body growth of GHRHΔGHR mice was associated with increases in GH secretion, mainly via higher pulsatile GH secretion and GH pulse amplitude. GHRHΔGHR female mice also showed increased GH pulse frequency and basal (non-pulsatile) secretion compared to control females. Liver Igf1 expression was increased only in GHRHΔGHR male mice. Mice carrying ablation of the insulin-like growth factor-1 (IGF-1) receptor (IGF1R) or both GHR and IGF1R in GHRH-expressing cells were generated. The increases in body growth and serum IGF-1 levels were significantly higher in GHRHΔGHR/IGF1R mice compared to GHRHΔGHR mice but similar to levels observed in GHRHΔIGF1R mice. Electrophysiological experiments showed no acute changes in the activity of GHRH neurons after GH or IGF-1 exposure. In conclusion, GH feeds back on GHRH cells to control the hypothalamic-pituitary-somatotropic axis. However, IGF1R signaling prevails over GHR as the primary signal sensed by GHRH neurons to regulate GH secretion.</p>","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Leptin Receptor Mutation Which Impairs Fertility in Ewes Causes Delayed Puberty in Male and Female Mice.","authors":"Rebecca A Lord, Megan A Inglis, Jennifer L Juengel, Greg M Anderson","doi":"10.1210/endocr/bqaf058","DOIUrl":"10.1210/endocr/bqaf058","url":null,"abstract":"<p><p>Reproductive function is tightly linked to nutritional status due to its high energetic demands. Leptin, a key adipose tissue-derived hormone signalling energy reserves to the brain, integrates metabolic status with the hypothalamic-pituitary-gonadal axis to ensure reproductive function is maintained or suppressed appropriately. Mutations in leptin or its receptor (LepR) are known to cause infertility and obesity in mice. In Davisdale ewes, 2 naturally occurring LepR mutations (R62C and P1019S) were associated with delayed puberty and subfertility, but their effects in males or in other species remain to be determined. This study examined the impact of analogous LepR mutations (A63C and P1018S) in mice using CRISPR-Cas9 gene editing. Puberty onset, adult fertility, and metabolic phenotypes were assessed in wild-type, heterozygous, and homozygous mutant mice. The A63C mutation, located in the extracellular domain of the receptor, resulted in increased body weight and adiposity in females, along with delays in puberty onset in both sexes. Despite these delays, adult reproductive function was maintained. Immunohistochemical analysis revealed no detectable reductions in leptin-induced pSTAT3, pERK1/2, or pmTOR signalling in the hypothalamic arcuate nucleus in either mutant line, indicating these pathways remain largely intact. These findings demonstrate the conserved importance of this region of the leptin receptor for puberty onset and adiposity across species, but also the resilience of leptin signalling in preserving reproductive function despite genetic variation.</p>","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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: \"Consensus PP1 Binding Motifs Regulate Transcriptional Corepression and Alternative RNA Splicing Activities of the Steroid Receptor Coregulators, p54nrb and PSF\".","authors":"","doi":"10.1210/endocr/bqaf068","DOIUrl":"https://doi.org/10.1210/endocr/bqaf068","url":null,"abstract":"","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":"166 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962728","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":"Type 2 Deiodinase Promotes Fatty Adipogenesis in Muscle Fibroadipogenic Progenitors From Adult Male Mice.","authors":"Cristina Luongo, Daniela Di Girolamo, Raffaele Ambrosio, Sara Di Cintio, Maria Angela De Stefano, Tommaso Porcelli, Domenico Salvatore","doi":"10.1210/endocr/bqaf050","DOIUrl":"10.1210/endocr/bqaf050","url":null,"abstract":"<p><p>Fibro-adipogenic progenitor cells (FAPs) are a heterogeneous population of multipotent mesenchymal cells that give rise to fibroblasts and adipocytes. In response to muscle injury, FAPs are activated and cooperate with inflammatory and muscle stem cells to promote muscle regeneration. In pathological conditions, such as muscular dystrophies, this coordinated response is partially lost and an accumulation of FAPs is observed that is responsible for maladaptive fibrosis, ectopic fat deposition, and impaired muscle regeneration. The role of intracellular thyroid hormone (TH) signaling in this cellular context is largely unknown. Here we show that intracellular 3,5,3'-triiodothyronine (T3) concentration in FAPs is increased in vitro during adipogenic differentiation via the increase of the T3-producing type 2 deiodinase (D2). The adipogenic potential is reduced in FAPs cultured in the presence of 3,3,5'-triiodothyronine (rT3), a specific D2 inhibitor, while exogenous administration of THs is able to induce the expression of relevant adipogenic genes. Accordingly, on genetic D2 depletion in vivo, adipogenesis was significantly reduced in D2KO compared to control mice. These data were confirmed using a FAP-inducible specific D2-KO mouse model, suggesting that a cell-specific D2-depletion in FAPs is sufficient to decrease fatty muscle infiltration and to improve muscle regeneration. Taken together, these data show that TH signaling is dynamically modulated in FAPs wherein D2-produced T3 is required to promote maturation of FAPs into adipocytes.</p>","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotensin Regulates Primate Ovulation Via Multiple Neurotensin Receptors.","authors":"Andrew C Pearson, Jessica S Miller, Hannah J Jensen, Ketan Shrestha, Thomas E Curry, Diane M Duffy","doi":"10.1210/endocr/bqaf041","DOIUrl":"10.1210/endocr/bqaf041","url":null,"abstract":"<p><p>Neurotensin (NTS), a small neuropeptide, was recently established as a key paracrine mediator of ovulation. NTS mRNA is highly expressed by granulosa cells in response to the luteinizing hormone surge, and multiple NTS receptors are expressed by cells of the ovulatory follicle. To identify the role of NTS receptors NTSR1 and SORT1 in ovulation in vivo, the dominant follicle of cynomolgus macaques (Macaca fascicularis) was injected with either vehicle control, the general NTS receptor antagonist SR142948, the NTSR1-selective antagonist SR48692, or the SORT1-selective antagonist AF38469. hCG was then administered to initiate ovulatory events. Ovulation was successful in all control-injected follicles. Rupture sites were smaller or absent after injection with NTS receptor antagonists. Histological analysis of follicles injected with SR142948, SR48692, or AF38469 revealed increased red blood cell extravasation and pooling in the follicle antrum when compared to controls. NTS receptor antagonist-injected follicles also showed dysregulated capillary formation and reduced luteinization of the granulosa cell layer. Prior in vitro studies showed that NTS significantly increased monkey ovarian microvascular endothelial cell (mOMEC) migration, while decreasing monolayer permeability. The NSTR1 antagonist SR48692 or siRNA knockdown of NTSR1 abrogated the ability of NTS to stimulate mOMEC migration and to decrease monolayer permeability. Similar experiments performed with the SORT1 antagonist AF38469 or siRNA knockdown of SORT1 also resulted in ablation of NTS-mediated changes in migration and permeability after SORT1 signaling was impaired. Together, these data implicate both NTSR1 and SORT1 to be critical mediators of NTS-stimulated ovulation, luteinization, and angiogenesis of the ovulatory follicle.</p>","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renin Finds a New Target.","authors":"Willis K Samson, Gina L C Yosten","doi":"10.1210/endocr/bqaf061","DOIUrl":"10.1210/endocr/bqaf061","url":null,"abstract":"","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763355","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":"Correction to: \"Ghrelin Promotes Functional Angiogenesis in a Mouse Model of Critical Limb Ischemia Through Activation of Proangiogenic MicroRNAs\".","authors":"","doi":"10.1210/endocr/bqaf044","DOIUrl":"https://doi.org/10.1210/endocr/bqaf044","url":null,"abstract":"","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":"166 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802735","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":"Transgenerational Effects of the Obesogen Tributyltin on Metabolic Health in Mice: Interactions With a Western Diet.","authors":"Richard C Chang, Yikai Huang, Kaitlin To, Ryan Scott Whitlock, Katelyn Uyen Nguyen, Michelle Clara Joemon, Miranda Lopez, Kritin Guy Deeprompt, Toshi Shioda, Bruce Blumberg","doi":"10.1210/endocr/bqaf063","DOIUrl":"10.1210/endocr/bqaf063","url":null,"abstract":"<p><p>Obesity is a global health crisis, with increasing evidence linking environmental factors such as exposure to endocrine-disrupting chemicals (EDCs) to its development. This study examines the transgenerational effects of exposure to the model obesogen, tributyltin (TBT), on obesity and metabolic health, specifically focusing on how these effects interact with a diet modeling the 50th percentile of US dietary consumption [the Total Western Diet (TWD)]. Pregnant F0 dams were exposed to TBT, and their offspring were subjected at adulthood to different diets, including a high-fat diet and TWD, across multiple subsequent generations (F1-F3). We found that TBT exposure predisposed male offspring to increased fat accumulation, insulin resistance, and metabolic dysfunction, effects that were exacerbated by the TWD. Notably, male offspring displayed elevated leptin levels, hepatic fibrosis, and inflammatory responses under TWD exposure, suggesting an additive or synergistic relationship between obesogen exposure and dietary fat intake. These transgenerational effects were largely absent in female offspring, underscoring sex-specific vulnerabilities to environmental and dietary factors. Our results demonstrated that the combination of prenatal TBT exposure and TWD amplifies metabolic disturbances across generations, highlighting the need to consider both environmental chemicals and dietary patterns in addressing the obesity pandemic. This study underscores the critical role of early-life EDC exposures and dietary factors in shaping long-term metabolic health and the potential for transgenerational programming of susceptibility to obesity and metabolic disorders.</p>","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}