Endocrine reviews最新文献_第8页

A State of Natriuretic Peptide Deficiency. 钠肽缺乏状态。

IF 20.3 1区医学

Endocrine reviews Pub Date : 2023-05-08 DOI: 10.1210/endrev/bnac029

Michael Nyberg, Dijana Terzic, Trine P Ludvigsen, Peter D Mark, Natasha B Michaelsen, Steen Z Abildstrøm, Mads Engelmann, A Mark Richards, Jens P Goetze

{"title":"A State of Natriuretic Peptide Deficiency.","authors":"Michael Nyberg, Dijana Terzic, Trine P Ludvigsen, Peter D Mark, Natasha B Michaelsen, Steen Z Abildstrøm, Mads Engelmann, A Mark Richards, Jens P Goetze","doi":"10.1210/endrev/bnac029","DOIUrl":"https://doi.org/10.1210/endrev/bnac029","url":null,"abstract":"Measurement of natriuretic peptides (NPs) has proven its clinical value as biomarker, especially in the context of heart failure (HF). In contrast, a state of partial NP deficiency appears integral to several conditions in which lower NP concentrations in plasma presage overt cardiometabolic disease. Here, obesity and type 2 diabetes have attracted considerable attention. Other factors-including age, sex, race, genetics, and diurnal regulation-affect the NP \"armory\" and may leave some individuals more prone to development of cardiovascular disease. The molecular maturation of NPs has also proven complex, with highly variable O-glycosylation within the biosynthetic precursors. The relevance of this regulatory step in post-translational propeptide maturation has recently become recognized in biomarker measurement/interpretation and cardiovascular pathophysiology. An important proportion of people appear to have reduced effective net NP bioactivity in terms of receptor activation and physiological effects. The state of NP deficiency both entails a potential for further biomarker development and could also offer novel pharmacological possibilities. Alleviating the state of NP deficiency before development of overt cardiometabolic disease in selected patients could be a future path for improving precision medicine.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 3","pages":"379-392"},"PeriodicalIF":20.3,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 4

Contemporary Biological Insights and Clinical Management of Craniopharyngioma. 颅咽管瘤的当代生物学见解和临床管理。

IF 20.3 1区医学

Endocrine reviews Pub Date : 2023-05-08 DOI: 10.1210/endrev/bnac035

John Richard Apps, Hermann Lothar Muller, Todd Cameron Hankinson, Torunn Ingrid Yock, Juan Pedro Martinez-Barbera

{"title":"Contemporary Biological Insights and Clinical Management of Craniopharyngioma.","authors":"John Richard Apps, Hermann Lothar Muller, Todd Cameron Hankinson, Torunn Ingrid Yock, Juan Pedro Martinez-Barbera","doi":"10.1210/endrev/bnac035","DOIUrl":"10.1210/endrev/bnac035","url":null,"abstract":"Craniopharyngiomas (CPs) are clinically aggressive tumors because of their invasive behavior and recalcitrant tendency to recur after therapy. There are 2 types based on their distinct histology and molecular features: the papillary craniopharyngioma (PCP), which is associated with BRAF-V600E mutations and the adamantinomatous craniopharyngioma (ACP), characterized by mutations in CTNNB1 (encoding β-catenin). Patients with craniopharyngioma show symptoms linked to the location of the tumor close to the optic pathways, hypothalamus, and pituitary gland, such as increased intracranial pressure, endocrine deficiencies, and visual defects. Treatment is not specific and mostly noncurative, and frequently includes surgery, which may achieve gross total or partial resection, followed by radiotherapy. In cystic tumors, frequent drainage is often required and intracystic instillation of drugs has been used to help manage cyst refilling. More recently targeted therapies have been used, particularly in PCP, but also now in ACP and clinical trials are underway or in development. Although patient survival is high, the consequences of the tumor and its treatment can lead to severe comorbidities resulting in poor quality of life, in particular for those patients who bear tumors with hypothalamic involvement. Accordingly, in these patients at risk for the development of a hypothalamic syndrome, hypothalamus-sparing treatment strategies such as limited resection followed by irradiation are recommended. In this review, we provide an update on various aspects of CP, with emphasis on recent advances in the understanding of tumor pathogenesis, clinical consequences, management, and therapies.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 3","pages":"518-538"},"PeriodicalIF":20.3,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542865","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

A Century-long Journey From the Discovery of Insulin to the Implantation of Stem Cell-derived Islets. 从胰岛素的发现到干细胞胰岛移植的百年历程。

IF 20.3 1区医学

Endocrine reviews Pub Date : 2023-03-04 DOI: 10.1210/endrev/bnac021

Adam Ramzy, Paul J Belmonte, Mitchell J S Braam, Shogo Ida, Emily M Wilts, Megan K Levings, Alireza Rezania, Timothy J Kieffer

{"title":"A Century-long Journey From the Discovery of Insulin to the Implantation of Stem Cell-derived Islets.","authors":"Adam Ramzy, Paul J Belmonte, Mitchell J S Braam, Shogo Ida, Emily M Wilts, Megan K Levings, Alireza Rezania, Timothy J Kieffer","doi":"10.1210/endrev/bnac021","DOIUrl":"https://doi.org/10.1210/endrev/bnac021","url":null,"abstract":"For the past century, insulin injections have saved millions of lives, but glycemic instability is still a persistent challenge for people with diabetes, leading to tremendous morbidity and premature mortality. Research in the field of islet transplantation has demonstrated that replacing insulin-producing β cells can restore euglycemia comparable to individuals without diabetes. However, a short supply of cadaveric islet donors, the technically challenging process of isolating islets, and the requirement for chronic immune suppression have impeded widespread clinical adoption. Rather than relying on cadaveric cells, pluripotent stem cells could serve as a virtually unlimited supply of insulin-producing β cells. Protocols have been developed that mimic the normal in vivo development of the human pancreas to generate pancreatic progenitor cells in vitro. Ongoing investigations have yielded progressively more mature β-like cells in vitro that produce insulin but do not yet fully mimic healthy mature β cells. Alongside development of differentiation protocols, other work has provided insight into potential implantation sites for stem cell-derived islet cells including the subcutaneous space, portal vein, and omentum. To optimize implanted cell survival and function, development of immune modulation therapies is ongoing, including selection of immunomodulatory medications and genetic modification of implanted cells to evade immune responses. Further, macroencapsulation or microencapsulation devices could be used to contain and/or immunoprotect implanted cells from the immune response including by using 3-dimensional bioprinting to facilitate the process. Remarkably, ongoing clinical trials have now yielded the first patient relying on differentiated stem cells rather than syringes as their insulin replacement therapy.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 2","pages":"222-253"},"PeriodicalIF":20.3,"publicationDate":"2023-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9145671","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: 12

Biological and Therapeutic Implications of the Tumor Microenvironment in Pituitary Adenomas. 垂体腺瘤肿瘤微环境的生物学和治疗意义。

IF 20.3 1区医学

Endocrine reviews Pub Date : 2023-03-04 DOI: 10.1210/endrev/bnac024

Mirela-Diana Ilie, Alexandre Vasiljevic, Philippe Bertolino, Gérald Raverot

{"title":"Biological and Therapeutic Implications of the Tumor Microenvironment in Pituitary Adenomas.","authors":"Mirela-Diana Ilie, Alexandre Vasiljevic, Philippe Bertolino, Gérald Raverot","doi":"10.1210/endrev/bnac024","DOIUrl":"https://doi.org/10.1210/endrev/bnac024","url":null,"abstract":"Pituitary adenomas (PAs) are neoplasms derived from the endocrine cells of the anterior pituitary gland. Most frequently, they are benign tumors, but may sometimes display an aggressive course, and in some cases metastasize. Their biology, including their wide range of behavior, is only partly understood. In terms of therapeutic targeting, most PAs are easily treated with available medical treatments, surgery, and sometimes radiotherapy. Nevertheless, gonadotroph adenomas lack medical therapeutic options, and treatment of aggressive PAs and pituitary carcinomas remains challenging. Here, we present an overview of the implications of the tumor microenvironment in PAs, reviewing its composition and function, as well as published cases that have been treated thus far using tumor microenvironment-targeting therapies. Additionally, we discuss emerging views, such as the concept of nonangiogenic tumors, and present perspectives regarding treatments that may represent future potential therapeutic options. Tumor-infiltrating lymphocytes, tumor-associated macrophages, folliculostellate cells, tumor-associated fibroblasts, angiogenesis, as well as the extracellular matrix and its remodeling, all have complex roles in the biology of PAs. They have been linked to hormone production/secretion, size, invasion, proliferation, progression/recurrence, and treatment response in PAs. From a therapeutic perspective, immune-checkpoint inhibitors and bevacizumab have already shown a degree of efficacy in aggressive PAs and pituitary carcinomas, and the use of numerous other tumor microenvironment-targeting therapies can be foreseen. In conclusion, similar to other cancers, understanding the tumor microenvironment improves our understanding of PA biology beyond genetics and epigenetics, and constitutes an important tool for developing future therapies.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 2","pages":"297-311"},"PeriodicalIF":20.3,"publicationDate":"2023-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9521257","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: 9

Hypoxia-Inducible Factor 2 Alpha (HIF2α) Inhibitors: Targeting Genetically Driven Tumor Hypoxia. 缺氧诱导因子2α (HIF2α)抑制剂:靶向基因驱动的肿瘤缺氧。

IF 20.3 1区医学

Endocrine reviews Pub Date : 2023-03-04 DOI: 10.1210/endrev/bnac025

Rodrigo A Toledo, Camilo Jimenez, Gustavo Armaiz-Pena, Carlota Arenillas, Jaume Capdevila, Patricia L M Dahia

{"title":"Hypoxia-Inducible Factor 2 Alpha (HIF2α) Inhibitors: Targeting Genetically Driven Tumor Hypoxia.","authors":"Rodrigo A Toledo, Camilo Jimenez, Gustavo Armaiz-Pena, Carlota Arenillas, Jaume Capdevila, Patricia L M Dahia","doi":"10.1210/endrev/bnac025","DOIUrl":"https://doi.org/10.1210/endrev/bnac025","url":null,"abstract":"Tumors driven by deficiency of the VHL gene product, which is involved in degradation of the hypoxia-inducible factor subunit 2 alpha (HIF2α), are natural candidates for targeted inhibition of this pathway. Belzutifan, a highly specific and well-tolerated HIF2α inhibitor, recently received FDA approval for the treatment of nonmetastatic renal cell carcinomas, pancreatic neuroendocrine tumors, and central nervous system hemangioblastomas from patients with von Hippel-Lindau disease, who carry VHL germline mutations. Such approval is a milestone in oncology; however, the full potential, and limitations, of HIF2α inhibition in the clinic are just starting to be explored. Here we briefly recapitulate the molecular rationale for HIF2α blockade in tumors and review available preclinical and clinical data, elaborating on mutations that might be particularly sensitive to this approach. We also outline some emerging mechanisms of intrinsic and acquired resistance to HIF2α inhibitors, including acquired mutations of the gatekeeper pocket of HIF2α and its interacting partner ARNT. Lastly, we propose that the high efficacy of belzutifan observed in tumors with genetically driven hypoxia caused by VHL mutations suggests that a focus on other mutations that similarly lead to HIF2α stabilization, such as those occurring in neuroendocrine tumors with disruptions in the tricarboxylic acid cycle (SDHA/B/C/D, FH, MDH2, IDH2), HIF hydroxylases (EGLN/PHDs), and the HIF2α-encoding gene, EPAS1, are warranted.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 2","pages":"312-322"},"PeriodicalIF":20.3,"publicationDate":"2023-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9882714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 10

Correction to: "Brown Adipose Tissue-A Translational Perspective". 更正:“棕色脂肪组织-翻译视角”。

IF 20.3 1区医学

Endocrine reviews Pub Date : 2023-03-04 DOI: 10.1210/endrev/bnac027

引用次数: 0

Correction to: "The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty". 更正:“与中枢性性早熟病因有关的先天和后天机制”。

IF 20.3 1区医学

Endocrine reviews Pub Date : 2023-03-04 DOI: 10.1210/endrev/bnac036

引用次数: 0

The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty. 中枢性性早熟病因中的先天和后天机制。

IF 20.3 1区医学

Endocrine reviews Pub Date : 2023-03-04 DOI: 10.1210/endrev/bnac020

Vinicius N Brito, Ana P M Canton, Carlos Eduardo Seraphim, Ana Paula Abreu, Delanie B Macedo, Berenice B Mendonca, Ursula B Kaiser, Jesús Argente, Ana Claudia Latronico

{"title":"The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty.","authors":"Vinicius N Brito, Ana P M Canton, Carlos Eduardo Seraphim, Ana Paula Abreu, Delanie B Macedo, Berenice B Mendonca, Ursula B Kaiser, Jesús Argente, Ana Claudia Latronico","doi":"10.1210/endrev/bnac020","DOIUrl":"10.1210/endrev/bnac020","url":null,"abstract":"The etiology of central precocious puberty (CPP) is multiple and heterogeneous, including congenital and acquired causes that can be associated with structural or functional brain alterations. All causes of CPP culminate in the premature pulsatile secretion of hypothalamic GnRH and, consequently, in the premature reactivation of hypothalamic-pituitary-gonadal axis. The activation of excitatory factors or suppression of inhibitory factors during childhood represent the 2 major mechanisms of CPP, revealing a delicate balance of these opposing neuronal pathways. Hypothalamic hamartoma (HH) is the most well-known congenital cause of CPP with central nervous system abnormalities. Several mechanisms by which hamartoma causes CPP have been proposed, including an anatomical connection to the anterior hypothalamus, autonomous neuroendocrine activity in GnRH neurons, trophic factors secreted by HH, and mechanical pressure applied to the hypothalamus. The importance of genetic and/or epigenetic factors in the underlying mechanisms of CPP has grown significantly in the last decade, as demonstrated by the evidence of genetic abnormalities in hypothalamic structural lesions (eg, hamartomas, gliomas), syndromic disorders associated with CPP (Temple, Prader-Willi, Silver-Russell, and Rett syndromes), and isolated CPP from monogenic defects (MKRN3 and DLK1 loss-of-function mutations). Genetic and epigenetic discoveries involving the etiology of CPP have had influence on the diagnosis and familial counseling providing bases for potential prevention of premature sexual development and new treatment targets in the future. Global preventive actions inducing healthy lifestyle habits and less exposure to endocrine-disrupting chemicals during the lifespan are desirable because they are potentially associated with CPP.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 2","pages":"193-221"},"PeriodicalIF":20.3,"publicationDate":"2023-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9940603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Brown Adipose Tissue-A Translational Perspective. 棕色脂肪组织--转化视角。

IF 22 1区医学

Endocrine reviews Pub Date : 2023-03-04 DOI: 10.1210/endrev/bnac015

André C Carpentier, Denis P Blondin, François Haman, Denis Richard

{"title":"Brown Adipose Tissue-A Translational Perspective.","authors":"André C Carpentier, Denis P Blondin, François Haman, Denis Richard","doi":"10.1210/endrev/bnac015","DOIUrl":"10.1210/endrev/bnac015","url":null,"abstract":"Brown adipose tissue (BAT) displays the unique capacity to generate heat through uncoupled oxidative phosphorylation that makes it a very attractive therapeutic target for cardiometabolic diseases. Here, we review BAT cellular metabolism, its regulation by the central nervous and endocrine systems and circulating metabolites, the plausible roles of this tissue in human thermoregulation, energy balance, and cardiometabolic disorders, and the current knowledge on its pharmacological stimulation in humans. The current definition and measurement of BAT in human studies relies almost exclusively on BAT glucose uptake from positron emission tomography with 18F-fluorodeoxiglucose, which can be dissociated from BAT thermogenic activity, as for example in insulin-resistant states. The most important energy substrate for BAT thermogenesis is its intracellular fatty acid content mobilized from sympathetic stimulation of intracellular triglyceride lipolysis. This lipolytic BAT response is intertwined with that of white adipose (WAT) and other metabolic tissues, and cannot be independently stimulated with the drugs tested thus far. BAT is an interesting and biologically plausible target that has yet to be fully and selectively activated to increase the body's thermogenic response and shift energy balance. The field of human BAT research is in need of methods able to directly, specifically, and reliably measure BAT thermogenic capacity while also tracking the related thermogenic responses in WAT and other tissues. Until this is achieved, uncertainty will remain about the role played by this fascinating tissue in human cardiometabolic diseases.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 2","pages":"143-192"},"PeriodicalIF":22.0,"publicationDate":"2023-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9985413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9504121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 Significance of Hypothalamic Inflammation and Gliosis for the Pathogenesis of Obesity in Humans. 下丘脑炎症和神经胶质瘤在人类肥胖发病中的意义。

IF 20.3 1区医学

Endocrine reviews Pub Date : 2023-03-04 DOI: 10.1210/endrev/bnac023

Leticia E Sewaybricker, Alyssa Huang, Suchitra Chandrasekaran, Susan J Melhorn, Ellen A Schur

{"title":"The Significance of Hypothalamic Inflammation and Gliosis for the Pathogenesis of Obesity in Humans.","authors":"Leticia E Sewaybricker, Alyssa Huang, Suchitra Chandrasekaran, Susan J Melhorn, Ellen A Schur","doi":"10.1210/endrev/bnac023","DOIUrl":"https://doi.org/10.1210/endrev/bnac023","url":null,"abstract":"Accumulated preclinical literature demonstrates that hypothalamic inflammation and gliosis are underlying causal components of diet-induced obesity in rodent models. This review summarizes and synthesizes available translational data to better understand the applicability of preclinical findings to human obesity and its comorbidities. The published literature in humans includes histopathologic analyses performed postmortem and in vivo neuroimaging studies measuring indirect markers of hypothalamic tissue microstructure. Both support the presence of hypothalamic inflammation and gliosis in children and adults with obesity. Findings predominantly point to tissue changes in the region of the arcuate nucleus of the hypothalamus, although findings of altered tissue characteristics in whole hypothalamus or other hypothalamic regions also emerged. Moreover, the severity of hypothalamic inflammation and gliosis has been related to comorbid conditions, including glucose intolerance, insulin resistance, type 2 diabetes, and low testosterone levels in men, independent of elevated body adiposity. Cross-sectional findings are augmented by a small number of prospective studies suggesting that a greater degree of hypothalamic inflammation and gliosis may predict adiposity gain and worsening insulin sensitivity in susceptible individuals. In conclusion, existing human studies corroborate a large preclinical literature demonstrating that hypothalamic neuroinflammatory responses play a role in obesity pathogenesis. Extensive or permanent hypothalamic tissue remodeling may negatively affect the function of neuroendocrine regulatory circuits and promote the development and maintenance of elevated body weight in obesity and/or comorbid endocrine disorders.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 2","pages":"281-296"},"PeriodicalIF":20.3,"publicationDate":"2023-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9899016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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: 4