Endocrine reviews最新文献

Immune checkpoint inhibitors in high-grade gastroenteropancreatic neuroendocrine neoplasms. 免疫检查点抑制剂在高级别胃肠胰神经内分泌肿瘤中的应用。

IF 20.3 1区医学

Endocrine reviews Pub Date : 2025-10-09 DOI: 10.1210/endrev/bnaf037

Nicola Fazio,Anna La Salvia

{"title":"Immune checkpoint inhibitors in high-grade gastroenteropancreatic neuroendocrine neoplasms.","authors":"Nicola Fazio,Anna La Salvia","doi":"10.1210/endrev/bnaf037","DOIUrl":"https://doi.org/10.1210/endrev/bnaf037","url":null,"abstract":"High-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (HG-NENs) comprise both highly proliferating well-differentiated NENs, called grade 3 NE tumors, NETs) and poorly differentiated NENs (also named NE carcinomas, NECs). The clinical management of these neoplasms poses unique challenges, and, while platinum plus etoposide is the first-line therapy in advanced setting of NECs, this is not the optimal regimen in G3 NETs in which other chemotherapy schemes, targeted agents and somatostatin analogues have shown to be active. However, overall response rates and clinical benefit are not satisfactory. Interestingly, HG-NENs may be a more suitable target for ICIs than low-grade NENs, because of their higher tumor mutational burden (TMB), increased PD-1 expression, probable increased PD-L1 expression and higher immune infiltration of tumor microenvironment. With these premises, few clinical trials have investigated the efficacy and safety of immune checkpoints inhibitors (ICIs) in HG GEP NENs. With our work we aimed to provide a comprehensive overview of the available literature data about ICIs' role in HG GEPNENs, by analyzing the critical points regarding study population, study design, study results, and potential useful biomarkers for selecting HG-GEP-NENs patients for ICI therapy.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"1 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Novel GLP-1-Based Medications for Type 2 Diabetes and Obesity. 基于glp -1的新型2型糖尿病和肥胖症药物。

IF 20.3 1区医学

Endocrine reviews Pub Date : 2025-10-07 DOI: 10.1210/endrev/bnaf036

Jang Won Son,Carel W le Roux,Matthias Blüher,Michael A Nauck,Soo Lim

{"title":"Novel GLP-1-Based Medications for Type 2 Diabetes and Obesity.","authors":"Jang Won Son,Carel W le Roux,Matthias Blüher,Michael A Nauck,Soo Lim","doi":"10.1210/endrev/bnaf036","DOIUrl":"https://doi.org/10.1210/endrev/bnaf036","url":null,"abstract":"The approvals of semaglutide and tirzepatide have set new benchmarks in the treatment of type 2 diabetes and obesity. Building on their success, novel GLP-1-based therapeutics are rapidly advancing. These next-generation agents engage not only GLP-1 receptors but also those for other gastro-entero-pancreatic hormones such as glucose-dependent insulinotropic polypeptide (GIP), glucagon, amylin, and peptide YY (PYY) to enhance energy uptake, storage, and expenditure through synergistic mechanisms. Both GIP receptor agonism and antagonism, particularly in combination with GLP-1 receptor agonism, have shown promise. Maridebart cafraglutide, combining GLP-1R agonism with GIPR antagonism, exemplifies this innovative approach. Glucagon co-agonists like survodutide and mazdutide have demonstrated significant weight loss and improved glycemic control. Amylin-based agents, including CagriSema (cagrilintide + semaglutide) and amycretin, enhance satiety and glycemic outcomes through complementary actions. Further innovation is seen in triple agonists such as retatrutide, which targets GIP, GLP-1, and glucagon receptors to amplify metabolic effects. Meanwhile, the emergence of orally active small-molecule GLP-1 receptor agonists like danuglipron and orforglipron, which are resistant to enzymatic degradation, marks a major advance in patient-friendly drug delivery. This review explores the mechanisms, clinical development, and therapeutic potential of these novel agents, excluding already approved drugs like liraglutide, semaglutide, and tirzepatide. We highlight how multi-receptor agonists and oral GLP-1-based therapies may reshape the future landscape of obesity and type 2 diabetes treatment by offering more effective and better-tolerated options.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"107 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Epidemiology, Genetic Etiology, and Intervention of Premature Ovarian Insufficiency. 卵巢功能不全的流行病学、遗传病因及干预措施。

IF 22 1区医学

Endocrine reviews Pub Date : 2025-09-16 DOI: 10.1210/endrev/bnaf011

Ting Guo, Hongyuan Liu, Bingying Xu, Yu Qi, Keyan Xu, Xinyi Wu, Xinmiao He, Yingying Qin, Zi-Jiang Chen

{"title":"Epidemiology, Genetic Etiology, and Intervention of Premature Ovarian Insufficiency.","authors":"Ting Guo, Hongyuan Liu, Bingying Xu, Yu Qi, Keyan Xu, Xinyi Wu, Xinmiao He, Yingying Qin, Zi-Jiang Chen","doi":"10.1210/endrev/bnaf011","DOIUrl":"10.1210/endrev/bnaf011","url":null,"abstract":"Premature ovarian insufficiency (POI) is a highly heterogeneous reproductive disorder in both its etiology and clinical presentation. The epidemiological characteristics of POI suggest that its occurrence likely involves a combination of genetic and environmental factors. Deciphering the pathogenic mechanisms of POI is crucial for improving reproductive outcomes as well as managing the long-term complications associated with ovarian dysfunction. Recent studies expand the list of POI causal genes and promote the viability of genetic diagnosis. However, whole exome sequencing studies in large-scale POI cohorts and genome-wide association studies on the age at natural menopause have uncovered a complex genetic architecture underlying POI that includes monogenic and oligogenic inheritance modes, emphasizing the difficulties in genetic diagnosis, especially for the isolated cases. Moreover, our understanding of the physiology of ovarian aging has greatly benefited from recent advances in multiomics analysis, expanding our perspective on the pathogenic mechanisms and potential targeted therapeutic strategies for POI. In this review, we summarize the epidemiological characteristics of POI, as well as progress in genetic and epigenetic etiologies, and discuss advances in pharmacology and material science that will likely contribute to new interventions for ovarian aging. Finally, this review offers new insights into prospects for early diagnosis and treatment of POI, while identifying persistent challenges and potential solutions to be addressed through future research.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":"621-651"},"PeriodicalIF":22.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Stress and Thyroid Function-From Bench to Bedside. 压力和甲状腺功能-从实验室到床边。

IF 22 1区医学

Endocrine reviews Pub Date : 2025-09-16 DOI: 10.1210/endrev/bnaf015

Katja Petrowski, George J Kahaly

{"title":"Stress and Thyroid Function-From Bench to Bedside.","authors":"Katja Petrowski, George J Kahaly","doi":"10.1210/endrev/bnaf015","DOIUrl":"10.1210/endrev/bnaf015","url":null,"abstract":"Experimental animal and human studies illustrate the effect of various stress forms on the thyroid gland and the regulation of thyroid hormones (THs) through the thyrotropic multiloop control circuit. The hypothalamic-pituitary-thyroid axis (HPT) axis is part of the physiological stress system and mediates key regulators of metabolic activity during stress response. Genetically characterized individuals are more affected in their response to stressors, and their psychological response is extremely amplified. This leads to significant increases in TH serum levels as soon as a negative stressor appears. Physical stressors are used to induce psychological stress (eg, physical exercise, starvation, sleep deprivation, hypoxia, and cold temperatures), all of which impact thyroid function. In addition, somatic illnesses may also affect the thyroid gland or may be related to a thyroidal dysfunction. As a psychosocial stressor in animal models, neonatal separation from the mother was used, affecting energy homeostasis and causing an increase in thyroliberin (TRH) expression in female rats and an increase in TRH degrading ectoenzyme in male rats. In mice with restrained stress, THs are important mediators of accelerated tumor growth. In human studies, isolated sexual abuse in childhood doubles the risk of thyroid dysfunction, with puerperal depression after sexual abuse in childhood increasing the risk for HPT axis disorders and elevated thyroid autoantibodies 4-fold. In addition, psychological illnesses influence thyroid function. In the future, laboratory studies with standardized induction of various stress forms are warranted to better understand stress-induced effects on the HPT axis and their corresponding mechanisms.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":"709-735"},"PeriodicalIF":22.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

DNA Damage and Repair in Thyroid Physiology and Disease. 甲状腺生理和疾病中的DNA损伤和修复。

IF 22 1区医学

Endocrine reviews Pub Date : 2025-09-11 DOI: 10.1210/endrev/bnaf035

Katarzyna D Arczewska, Dorota Sys, Hilde L Nilsen, Agnieszka Piekiełko-Witkowska

{"title":"DNA Damage and Repair in Thyroid Physiology and Disease.","authors":"Katarzyna D Arczewska, Dorota Sys, Hilde L Nilsen, Agnieszka Piekiełko-Witkowska","doi":"10.1210/endrev/bnaf035","DOIUrl":"https://doi.org/10.1210/endrev/bnaf035","url":null,"abstract":"The thyroid is exposed to DNA damage induced by normal physiological processes (eg, oxidative stress resulting from thyroid hormone synthesis or mitochondrial respiration) or through environmental insults (eg, environmental pollutants, ionizing radiation exposure). Robust antioxidative stress defense and DNA repair mechanisms protect thyrocyte genome integrity, but defective or dysregulated DNA repair pathways have been implicated in thyroid pathology, including autoimmune thyroid disease and thyroid malignancy. In thyroid cancer, disturbed antioxidative stress defense, Mismatch Repair, Non-Homologous End-Joining, or DNA damage response pathways contribute to both the onset and progression of the disease. The insight into mechanisms governing thyrocyte genome integrity may help to gain better understanding of the pathology and suggest novel therapeutic regimens, urgently needed in treatment-refractory disease. In the current review, we provide comprehensive description of the exogenous and endogenous factors, as well as DNA repair mechanisms influencing thyrocyte genome integrity. Moreover, we pinpoint major research avenues that should be pursued in future research. This information will be valuable in directing new discoveries to better understand thyroid disease pathomechanisms, as well as aid development of novel diagnostic and therapeutic tools.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":""},"PeriodicalIF":22.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Advances in Adipose Tissue Biology. 脂肪组织生物学进展。

IF 22 1区医学

Endocrine reviews Pub Date : 2025-09-11 DOI: 10.1210/endrev/bnaf032

Silvia Corvera, Akhila Rajan, Kristy L Townsend, Farnaz Shamsi, Jun Wu, Katrin J Svensson, Lori M Zeltser, Sheila Collins, Tânia Reis, Yu-Hua Tseng, Laurie J Goodyear

引用次数: 0

Glycerol and glycerol-3-phosphate: multifaceted metabolites in metabolism, cancer and other diseases. 甘油和甘油-3-磷酸：代谢、癌症和其他疾病中的多方面代谢物。

IF 20.3 1区医学

Endocrine reviews Pub Date : 2025-09-10 DOI: 10.1210/endrev/bnaf033

S R Murthy Madiraju,Elite Possik,Fahd Al-Mulla,Christopher J Nolan,Marc Prentki

{"title":"Glycerol and glycerol-3-phosphate: multifaceted metabolites in metabolism, cancer and other diseases.","authors":"S R Murthy Madiraju,Elite Possik,Fahd Al-Mulla,Christopher J Nolan,Marc Prentki","doi":"10.1210/endrev/bnaf033","DOIUrl":"https://doi.org/10.1210/endrev/bnaf033","url":null,"abstract":"Glycerol and glycerol-3-phosphate are key metabolites at the intersection of carbohydrate, lipid and energy metabolism. Their production and usage are organismal and cell type specific. Glycerol has unique physicochemical properties enabling it to function as an osmolyte, protein structure stabilizer, antimicrobial and antifreeze agent, important to preservation of many biological functions. Glycerol and glycerol-3-phosphate are implicated in many physiological and disease processes relating to energy metabolism, thermoregulation, hydration, skin health, male fertility, aging, and cancer. Glycerol has countless applications in the food, pharmaceutical and cosmetics industries. It is used as a sweetener, preservative, thickening agent, humectant, osmolyte and cryoprotectant. It is widely used in skin and wound care products, laxatives, in cell and tissue preservation and in medicines for numerous conditions. Here, we review the multiple uses and functions of glycerol and glycerol-3-phosphate and associated transporters, enzymes and target genes in health, senescence and disease. We discuss the evidence that glycerol may be present at much higher levels in tissues and cells than in the blood. We bring particular focus to the newly identified glycerol shunt in the direct formation of glycerol independent of lipolysis and as a pathway allowing cells to adapt to various stresses. Relevant to chronic metabolic diseases, cancer and aging, glycerol and glycerol-3-phosphate presents important translational implications and thus warrants much more attention.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"24 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Cognitive Assessment in Adults with Adrenal Cortisol Insufficiency: Challenges and Opportunities. 成人肾上腺皮质醇不全的认知评估：挑战与机遇。

IF 22 1区医学

Endocrine reviews Pub Date : 2025-09-03 DOI: 10.1210/endrev/bnaf029

Anat Ben-Shlomo, Michelle Koh, Sarah A Kremen, Jeffrey Wertheimer

引用次数: 0

Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis. 肝糖皮质激素受体作用与葡萄糖稳态。

IF 22 1区医学

Endocrine reviews Pub Date : 2025-09-02 DOI: 10.1210/endrev/bnaf030

Maggie Chang, Jen-Chywan Wang

{"title":"Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.","authors":"Maggie Chang, Jen-Chywan Wang","doi":"10.1210/endrev/bnaf030","DOIUrl":"10.1210/endrev/bnaf030","url":null,"abstract":"One of the major metabolic functions of glucocorticoids (GC) is to maintain circulating glucose levels during stress, as glucose is the preferred energy source for the brain. Because of their potent anti-inflammatory and immune modulatory activities, GC are frequently used to treat inflammatory and autoimmune diseases. Chronic GC exposure, which can be a result from long-term GC pharmacotherapy and prolonged stress, however, causes undesired adverse effects that include hyperglycemia and insulin resistance. These adverse effects limit the application of GC therapy. GC act through an intracellular GC receptor (GR), a transcriptional regulator, to modulate the transcriptional rate of specific genes to exert physiological responses. The liver is a major target tissue of GC to modulate glucose homeostasis. In this review, we discuss the mechanisms of GR-activated transcription of genes involved in glucose metabolism and how hepatic GR primary target genes participate in the regulation of insulin sensitivity and glucose homeostasis. Transcriptional coregulators involved in GR-regulated transcription of glucose metabolism genes and signaling pathways specifically activated upon chronic GC exposure to induce glucose disorders are introduced. Metabolic profiles of liver-specific GR knockout mice are also reviewed. Finally, individual-specific GC responses and mechanisms underlying these phenomena are discussed. Overall, more extensive studies of the mechanisms of GR-regulated hepatic glucose homeostasis not only will expand our knowledge of the regulation of metabolic homeostasis but are also critical for developing improved GC pharmacotherapy and novel approaches to tackle metabolic disorders by targeting GR.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":""},"PeriodicalIF":22.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Correction to: "Glucose-Dependent Insulinotropic Polypeptide in Incretin Physiology: Role in Health and Disease". 更正：“肠促胰岛素生理学中的葡萄糖依赖性胰岛素多肽：在健康和疾病中的作用”。

IF 20.3 1区医学

Endocrine reviews Pub Date : 2025-08-20 DOI: 10.1210/endrev/bnaf028

引用次数: 0