Endocrinology最新文献_第3页

Correction to: "Tenascin-C Potentiates Wnt Signaling in Thyroid Cancer".

IF 3.8 3区医学

Endocrinology Pub Date : 2025-02-27 DOI: 10.1210/endocr/bqaf053

引用次数: 0

Ablation of Leptin Receptor Signaling Alters Somatotrope Transcriptome Maturation in Female Mice.

IF 3.8 3区医学

Endocrinology Pub Date : 2025-02-27 DOI: 10.1210/endocr/bqaf036

Tiffany K Miles, Angela K Odle, Stephanie D Byrum, Alex N Lagasse, Anessa C Haney, Victoria G Ortega, Ashley K Herdman, Melanie C MacNicol, Angus M MacNicol, Gwen V Childs

{"title":"Ablation of Leptin Receptor Signaling Alters Somatotrope Transcriptome Maturation in Female Mice.","authors":"Tiffany K Miles, Angela K Odle, Stephanie D Byrum, Alex N Lagasse, Anessa C Haney, Victoria G Ortega, Ashley K Herdman, Melanie C MacNicol, Angus M MacNicol, Gwen V Childs","doi":"10.1210/endocr/bqaf036","DOIUrl":"10.1210/endocr/bqaf036","url":null,"abstract":"Anterior pituitary somatotropes respond to metabolic signals from the adipokine leptin to optimize functional responses to the body's nutritional state via growth hormone (GH) secretion. Molecular targets of leptin in pituitary somatotropes include GH, the GH-releasing hormone receptor (GHRHR), and, in females, the transcription factor POU1F1, all of which are dependent on leptin stimulation for expression. To identify the trophic mechanisms underlying leptin action upon somatotropes, we analyzed single-cell gene transcriptomes comparing pituitaries from a female mouse model bearing somatotropes lacking leptin receptors (LEPR-null mutants) and control pituitaries. Computational clustering of results identified all common pituitary cell types and differentially expressed genes. Mutant female somatotrope clusters showed decreased levels of Gh and Htatsf1 mRNA, which was also reduced in mutant pituitaries lacking Prop1 or POU1F1. Mutant somatotropes also showed increased expression of markers for pituitary stem and progenitor cells (eg, Sox9) and increased (1.73-6.7 fold) expression of nonsomatotrope hormones, Pomc, Lhb, Tshb, Cga, and Prl. Conversely, the mutant female Sox2-positive stem cell cluster showed decreased expression of markers for stem cells and increased expression of pituitary hormone genes. The data support a model in which the female pituitary somatotrope cell population's development and/or maintenance requires leptin trophic signals and also suggests that, in the absence of normal somatotrope maturation, pituitary stem cells are driven towards premature differentiation.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448259","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}

引用次数: 0

The Evolving Role of PTH Signaling in Osteocytes.

IF 3.8 3区医学

Endocrinology Pub Date : 2025-02-27 DOI: 10.1210/endocr/bqaf034

Gokce Kiryaman, Irobosa Enabulele, Myra L Banville, Paola Divieti Pajevic

{"title":"The Evolving Role of PTH Signaling in Osteocytes.","authors":"Gokce Kiryaman, Irobosa Enabulele, Myra L Banville, Paola Divieti Pajevic","doi":"10.1210/endocr/bqaf034","DOIUrl":"10.1210/endocr/bqaf034","url":null,"abstract":"Over the past decade, advancements in cell line development and genetic tools have led to a wealth of new insights into the effects of parathyroid hormone (PTH), particularly on osteocytes-cells deeply embedded within the bone's mineral matrix. These cells were once believed to be inactive bystanders, with little, if any, role in skeletal and mineral homeostasis. This concept of passive osteocytes has been challenged in recent years and osteocytes are now recognized for their crucial functions in skeletal mechanotransduction, bone modeling and remodeling, mineral ion regulation, and hematopoiesis. Moreover, osteocytes are key targets of PTH, and studies utilizing genetically modified mice, in which the PTH receptor is either deleted or overexpressed, have shed light on the hormone's complex effects on these cells. Several signaling molecules, including salt kinase inhibitors and histone deacetylases, have been identified as part of PTH's intracellular signaling cascade. In addition to its effects on bone metabolism, PTH has also been implicated in regulating bone energy metabolism, skeletal aging, and hematopoiesis. This review summarizes both classical and emerging effects of PTH on osteocytes, highlights the limitations of current research, and offers perspectives for future investigations in the field.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413793","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}

引用次数: 0

Effects of Endocrine-Disrupting Chemicals on Adrenal Function.

IF 3.8 3区医学

Endocrinology Pub Date : 2025-02-27 DOI: 10.1210/endocr/bqaf045

Zixuan Li, Bernard Robaire

{"title":"Effects of Endocrine-Disrupting Chemicals on Adrenal Function.","authors":"Zixuan Li, Bernard Robaire","doi":"10.1210/endocr/bqaf045","DOIUrl":"10.1210/endocr/bqaf045","url":null,"abstract":"The adrenal glands play crucial roles in regulating metabolism, blood pressure, immune system function, and response to stress through the secretion of hormones. Despite their critical functions, the adrenal glands are often overlooked in studies on the effects of potential toxicants. Research across human, animal, and in vitro studies has identified more than 60 compounds that can induce adrenocortical toxicity. These compounds, known as endocrine-disrupting chemicals (EDCs), are natural or synthetic substances that interfere with the endocrine system. This review aims to provide an overview of the effects of 4 major families of EDCs-flame retardants, bisphenols, phthalates, and microplastics-on the function of the adrenal glands. The PubMed database was searched for studies reporting the effects of the chemicals in these 4 families on the adrenal glands. There is clear evidence that the morphology and function of the adrenal gland are affected, particularly through disrupting the steroidogenic pathway. Additionally, some EDCs have been shown to exert transgenerational effects, raising further concerns about their long-term effect. However, most EDCs have not been thoroughly evaluated for their effects on the function of the adrenal glands, especially in human studies. Thus, developing regulatory testing guideline to include the adrenal glands in the screening of EDCs is urgently needed.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572563","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}

引用次数: 0

Single-Cell Landscape of Peripheral Blood Mononuclear Cells in Patients With Graves Disease.

IF 3.8 3区医学

Endocrinology Pub Date : 2025-02-27 DOI: 10.1210/endocr/bqaf038

Yixuan Wang, Xinjie Zhang, Junfeng Ge, Jiajia Jin, Zhijian Zheng, Jiaxuan Li, Xiaowei Wang, Shucui Zhang, Zhe Wang, Guangguo Dong

{"title":"Single-Cell Landscape of Peripheral Blood Mononuclear Cells in Patients With Graves Disease.","authors":"Yixuan Wang, Xinjie Zhang, Junfeng Ge, Jiajia Jin, Zhijian Zheng, Jiaxuan Li, Xiaowei Wang, Shucui Zhang, Zhe Wang, Guangguo Dong","doi":"10.1210/endocr/bqaf038","DOIUrl":"10.1210/endocr/bqaf038","url":null,"abstract":"Context: Graves disease (GD) is a thyroid-specific autoimmune disease and the most common cause of hyperthyroidism. Its pathogenesis is associated with the disruption of immune tolerance and autoantibody production. However, the mechanisms underlying immune abnormalities remain incompletely elucidated.Objective: To investigate changes in the cellular composition and function of peripheral blood mononuclear cells (PBMCs) in GD patients at single-cell resolution.Methods: We employed single-cell RNA sequencing (scRNA-seq) and analyzed 22 680 peripheral blood mononuclear cells (PBMCs) from 8 GD patients and 12 healthy controls.Results: Our results unveiled the single-cell landscape of PBMCs in GD patients, revealing substantial heterogeneity and changes in the cellular composition and function of PBMCs. We observed an increase in the proportion of CD16+ natural killer (NK) cells and memory cells in T and B lymphocyte subsets. This increase was accompanied by significantly enhanced functions, including cell activation, immune/defense responses, and inflammatory reactions. Additionally, we detected changes in the activity of transcription factors in various cell types, which were linked to the regulation of genes critical for immune and inflammation responses. Furthermore, we found a reduction in communication between NK cells and other immune cells, including CD4+ T cells, monocytes, and B cells, mediated by killer cell immunoglobulin-like receptor (KIR)-like inhibitory receptors, suggesting their involvement in the pathogenesis of GD.Conclusion: Our study revealed characteristic alterations in the composition and function of immune cell subsets in the PBMCs of GD patients. These findings shed light on the mechanisms underlying immune dysregulation in GD.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491286","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}

引用次数: 0

Role of Protein Regulators of Cholesterol Homeostasis in Immune Modulation and Cancer Pathophysiology.

IF 3.8 3区医学

Endocrinology Pub Date : 2025-02-27 DOI: 10.1210/endocr/bqaf031

Yu Wang, Shruti V Bendre, Steven A Krauklis, Andrew J Steelman, Erik R Nelson

引用次数: 0

Deciphering Sperm-Carried IGF2 Transcript Variants: Cloning, qPCR Detection, and Variant Analysis.

IF 3.8 3区医学

Endocrinology Pub Date : 2025-02-27 DOI: 10.1210/endocr/bqaf035

Rossella Cannarella, Mangesh Suryavanshi, Aldo E Calogero, Nina Desai, Scott D Lundy, Aaron W Miller

{"title":"Deciphering Sperm-Carried IGF2 Transcript Variants: Cloning, qPCR Detection, and Variant Analysis.","authors":"Rossella Cannarella, Mangesh Suryavanshi, Aldo E Calogero, Nina Desai, Scott D Lundy, Aaron W Miller","doi":"10.1210/endocr/bqaf035","DOIUrl":"10.1210/endocr/bqaf035","url":null,"abstract":"Context: The insulin-like growth factor 2 (IGF2) gene, a paternally imprinted gene inactive in oocytes, plays a vital role in early embryo development. While 5 IGF2 variants have been described, the specific variants expressed in human spermatozoa compared to granulosa cells (GCs) remain unclear.Objective: To characterize the quantity and variants of IGF2 transcripts expressed in human spermatozoa.Methods: Post-gradient sperm samples were collected from 2 healthy, fertile men with normal semen parameters, while GCs were isolated following an oocyte retrieval procedure of a woman undergoing in vitro fertilization due to male factor infertility. RNA extraction, cDNA synthesis, PCR amplification, and cloning were performed. PCR products were ligated into PCR4-TOPO vectors and transformed into Escherichia coli DH-10α. A total of 96 positive clones (32 per sample) were characterized via Sanger sequencing to identify variants. Quantitative PCR (qPCR) with gene-specific primers analyzed transcript quantities, single nucleotide polymorphisms (SNPs), product sizes, and melting temperatures.Results: Of the 96 true-positive IGF2 cDNA clones, 14 distinct variants were identified, including deletions, insertions, and SNPs, resulting in amino acid sequence changes. Two common variants were present in both sperm and GCs, while 2 were GC-specific, and the remaining were exclusive to spermatozoa. Some clustered with known NCBI variants, while others formed 2 novel phylogenetic clusters.Conclusion: This study expands the repertoire of IGF2 variants and highlights differences between spermatozoa and GC transcripts. It is the first to analyze IGF2 variants in sperm from fertile men, paving the way for future research into their role in embryogenesis.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412745","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}

引用次数: 0

Inhibition of TSH Receptor Expression by a Cyclotriazadisulfonamide as a Potential Treatment of Graves Hyperthyroidism.

IF 3.8 3区医学

Endocrinology Pub Date : 2025-02-27 DOI: 10.1210/endocr/bqaf037

Christine C Krieger, Susanne Neumann, Xiangliang Sui, Jay Scott Templin, Topprasad Kapri, Violeta G Demillo, Ryan K Olsen, Amarawan Intasiri, Marvin C Gershengorn, Thomas W Bell

{"title":"Inhibition of TSH Receptor Expression by a Cyclotriazadisulfonamide as a Potential Treatment of Graves Hyperthyroidism.","authors":"Christine C Krieger, Susanne Neumann, Xiangliang Sui, Jay Scott Templin, Topprasad Kapri, Violeta G Demillo, Ryan K Olsen, Amarawan Intasiri, Marvin C Gershengorn, Thomas W Bell","doi":"10.1210/endocr/bqaf037","DOIUrl":"10.1210/endocr/bqaf037","url":null,"abstract":"Graves hyperthyroidism (GH) is a condition in which autoantibodies chronically activate the thyrotropin (TSH) receptor (TSHR). TSHR is one of the few G protein-coupled receptors (GPCRs) predicted to have a signal peptide, making it a potential target for cyclotriazadisulfonamide (CADA) compounds. We sought to determine whether a small-molecule drug that selectively induces nascent protein degradation could decrease TSHR expression in vitro and in vivo at therapeutically relevant levels. We tested several CADA compounds for their ability to reduce TSHR surface expression in HEK 293 cells overexpressing human TSHR (HEK-TSHR cells) using flow cytometry. Inhibition of downstream cAMP production and thyroglobulin (Tg) secretion were measured in HEK-TSHR and human thyrocytes, respectively. Follow-up studies in VGD040-treated BALB/c mice assessed plasma levels of free T4 in response to TSH stimulation. Among a number of CADA analogues, VGD040 decreased TSHR at the surface of HEK-TSHR cells. VGD040 was found to be selective toward TSHR compared to similar glycoprotein hormone receptors. In human thyrocytes, reduction of TSHR surface expression by VGD040 decreased cyclic adenosine monophosphate production and Tg secretion. Most important, VGD040 decreased TH secretion in mice without apparent toxicity at the effective dose studied. VGD040 is an important new lead with potential for developing safe drug treatments for GH.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448224","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}

引用次数: 0

Body Mass Index and Risk of All-Cause and Cardiovascular Disease Mortality in Patients With Type 2 Diabetes Mellitus.

IF 3.8 3区医学

Endocrinology Pub Date : 2025-02-27 DOI: 10.1210/endocr/bqaf040

Cui Wu, Yuandong Li, Na Li, Ka Kei Chan, Chunli Piao

{"title":"Body Mass Index and Risk of All-Cause and Cardiovascular Disease Mortality in Patients With Type 2 Diabetes Mellitus.","authors":"Cui Wu, Yuandong Li, Na Li, Ka Kei Chan, Chunli Piao","doi":"10.1210/endocr/bqaf040","DOIUrl":"10.1210/endocr/bqaf040","url":null,"abstract":"Context: The correlations between body mass index (BMI) and risk of all-cause and cardiovascular disease (CVD) mortality in patients with type 2 diabetes mellitus (T2DM) are still controversial.Objective: To explore the correlation between BMI and the risk of all-cause and CVD mortality in patients with T2DM.Methods: The data sources China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed, Web of Science, Embase, and The Cochrane Library were searched up until May 25, 2024. After adjusting for confounding factors, the original study on the association between BMI and all-cause and CVD mortality in patients with T2DM was analyzed. Number of all-cause and CVD mortality events, BMI, and basic characteristics were extracted.Results: Twenty-eight papers with a total of 728 321 participants were finally included. Compared to normal-weight patients with T2DM, the risk of all-cause (HR = 1.61; 95% CI [1.51, 1.72]; P = .000) and CVD (HR = 1.31; 95% CI [1.10, 1.54]; P = .002) mortality were increased in underweight patients; however, they were reduced (HR = 0.85; 95% CI [0.81, 0.89]; P = .000) and (HR = 0.86; 95% CI [0.78, 0.96]; P = .007), respectively in patients with overweight. Also, there were significant reductions in the risk of all-cause (HR = 0.85; 95% CI [0.78, 0.92]; P = .000) and CVD (HR = 0.81; 95% CI [0.74, 0.89]; P = .000] mortality in patients with mild obesity. The difference in the risk of all-cause mortality (HR = 0.98; 95% CI [0.80, 1.21]; P = .881) in patients with moderate obesity was not statistically significant.Conclusion: We found that there were correlations between BMI and the risk of all-cause and CVD mortality in patients with T2DM. The obesity paradox remains.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556242","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}

引用次数: 0

Selective Therapeutic Potential of a H2O2-Inducible DNA Interstrand Cross-linker in Anaplastic Thyroid Carcinoma.

IF 3.8 3区医学

Endocrinology Pub Date : 2025-02-27 DOI: 10.1210/endocr/bqaf029

Chenghui Lu, Dehao Yu, Xufu Wang, Jiao Li, Yingying Zhang, Congcong Wang, Qiang Jia, Jian Tan, Wei Zheng, Huabing Sun, Zhaowei Meng

{"title":"Selective Therapeutic Potential of a H2O2-Inducible DNA Interstrand Cross-linker in Anaplastic Thyroid Carcinoma.","authors":"Chenghui Lu, Dehao Yu, Xufu Wang, Jiao Li, Yingying Zhang, Congcong Wang, Qiang Jia, Jian Tan, Wei Zheng, Huabing Sun, Zhaowei Meng","doi":"10.1210/endocr/bqaf029","DOIUrl":"10.1210/endocr/bqaf029","url":null,"abstract":"We aimed to investigate hydrogen peroxide-inducible DNA interstrand cross-link (HP-ICL) as a targeted therapy for anaplastic thyroid cancer (ATC) due to its higher H2O2 content than normal cells. In vitro analysis included fluorescence microscopy for H2O2 levels and exposure of ATC cells to various HP-ICL concentrations followed by assessment of cell viability, apoptosis, cell cycle, and DNA damage using methyl thiazolyl tetrazolium (MTT), flow cytometry, and a γH2AX assay. Protein levels related to apoptosis and the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway were measured by Western blotting. An ATC xenograft mouse model was used to evaluate the HP-ICL's in vivo effects. ATC cells had higher H2O2 levels than normal thyroid cells. HP-ICL treatment caused a dose-dependent decrease in cell viability and an increase in apoptosis, with a slight G2/M phase arrest. A 30 µM HP-ICL treatment doubled γH2AX foci. Bcl-2 levels decreased, while Bax, cleaved-Caspase 3, and PARP increased in a dose-dependent manner. It also inhibited p-PI3K, p-AKT, and p-mTOR. In vivo, the HP-ICL significantly inhibited tumor growth while maintaining body weight and without causing organ damage or altering thyroid hormone levels. Additionally, tumor sections exhibited increased TUNEL staining, decreased Ki67 expression, and reduced levels of p-PI3K, p-AKT, and p-mTOR. The HP-ICL significantly inhibited ATC both in vitro and in vivo, suggesting its potential as an effective therapy for ATC.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412928","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}

引用次数: 0