Nature Reviews Endocrinology最新文献

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Progesterone in pregnancy
IF 40.5 1区 医学
Nature Reviews Endocrinology Pub Date : 2025-03-31 DOI: 10.1038/s41574-025-01106-y
Claire Greenhill
{"title":"Progesterone in pregnancy","authors":"Claire Greenhill","doi":"10.1038/s41574-025-01106-y","DOIUrl":"https://doi.org/10.1038/s41574-025-01106-y","url":null,"abstract":"<p>Maternal sex steroid hormones (such as oestrogen and progesterone) are known to have important roles in reproduction, contributing to maintaining pregnancy and to embryonic development. However, how maternal progesterone might influence the embryo and the maternal metabolism has been unclear; a new study set out to investigate this question.</p><p>The researchers focused on membrane progesterone receptor ε (mPRε), which is one of five progesterone receptors and is highly expressed in adipose tissue. Using an mPRε-deficient mouse model, the researchers showed that progesterone activated mPRε in white adipose tissue, which could promote insulin resistance. Moreover, in pregnancy, mPRε-deficient mice had better insulin sensitivity than wild-type mice, even though plasma levels of progesterone and insulin were similar between the two groups.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"72 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736650","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 new model predicts the best medication for patients with type 2 diabetes mellitus
IF 40.5 1区 医学
Nature Reviews Endocrinology Pub Date : 2025-03-26 DOI: 10.1038/s41574-025-01105-z
Olivia Tysoe
{"title":"A new model predicts the best medication for patients with type 2 diabetes mellitus","authors":"Olivia Tysoe","doi":"10.1038/s41574-025-01105-z","DOIUrl":"https://doi.org/10.1038/s41574-025-01105-z","url":null,"abstract":"<p>Many glucose-lowering medications for type 2 diabetes mellitus (T2DM) have varying levels of efficacy in different patients, but it is currently not well understood which criteria should be used to personalize T2DM treatment. A study published in <i>The Lancet</i> has developed a model to predict the efficacy of different T2DM drug classes in reducing glycaemia in patients, based on routinely recorded clinical features.</p><p>The model was developed using primary and secondary care healthcare records from people in the UK aged 18–79 with T2DM, taken from the Clinical Practice Research Datalink (CPRD) database. The primary outcome predicted by the model was a patient’s HbA<sub>1c</sub> level 12 months after drug initiation for each of the five drug classes. The model’s accuracy was validated by comparing predicted and actual HbA<sub>1c</sub> values for the drug classes in three randomized controlled trials.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"71 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703044","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 novel anti-obesity peptide that targets the hypothalamus
IF 40.5 1区 医学
Nature Reviews Endocrinology Pub Date : 2025-03-24 DOI: 10.1038/s41574-025-01104-0
Senegal Carty
{"title":"A novel anti-obesity peptide that targets the hypothalamus","authors":"Senegal Carty","doi":"10.1038/s41574-025-01104-0","DOIUrl":"https://doi.org/10.1038/s41574-025-01104-0","url":null,"abstract":"<p>Computational tools that predict which amino acid sequences are produced by cleavage enzymes can accelerate the discovery of bioactive peptides with therapeutic potential. A study recently published in <i>Nature</i> presents a peptide prediction programme that was used to search for novel anti-obesity peptides made by prohormone convertase enzymes (also known as proprotein convertase subtilisin/kexin (PCSK) enzymes).</p><p>After using their programme to predict the amino acid sequences of putative peptide products of PCSK enzyme activity, the team created a library containing 100 predicted peptides that had no known function. Next, they tested which of these peptides might be able to influence neuronal signalling and pancreatic β-cell activity to regulate metabolism. They treated cells from a rat phaeochromocytoma cell line and cells from a rat β-cell line with the peptides, then measured changes in <i>Fos</i> mRNA transcription. BRP, which is a predicted product of PCSK cleavage of the protein BRINP2, elicited a notable increase in <i>Fos</i> expression in both of the cell lines. To confirm whether BRP is produced in humans and in mice, the researchers performed liquid chromatography–mass spectrometry on samples of cerebrospinal fluid from human donors and mouse brain tissue. Their results showed that BRP was present in both sample types. They also tested whether PCSK1 produces BRP in vivo by measuring brain levels of BRP in wild-type mice and in transgenic mice in which PCSK1 function is impaired. They found that the levels of BRP were considerably reduced in the brains of the transgenic mice, which suggests that PCSK1 activity contributes to BRP production.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"17 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677707","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
Steroid hormones as modulators of anti-tumoural immunity
IF 40.5 1区 医学
Nature Reviews Endocrinology Pub Date : 2025-03-24 DOI: 10.1038/s41574-025-01102-2
Paul Schwarzlmueller, Alexandra Triebig, Guillaume Assié, Anne Jouinot, Sebastian Theurich, Tanja Maier, Felix Beuschlein, Sebastian Kobold, Matthias Kroiss
{"title":"Steroid hormones as modulators of anti-tumoural immunity","authors":"Paul Schwarzlmueller, Alexandra Triebig, Guillaume Assié, Anne Jouinot, Sebastian Theurich, Tanja Maier, Felix Beuschlein, Sebastian Kobold, Matthias Kroiss","doi":"10.1038/s41574-025-01102-2","DOIUrl":"https://doi.org/10.1038/s41574-025-01102-2","url":null,"abstract":"<p>Immune evasion is a hallmark of cancer progression but the role of steroid hormones in this evasion has long been underrated. This oversight is particularly notable for glucocorticoids given that exogenous glucocorticoids remain a cornerstone therapy in various oncological treatment regimens, supportive care and treatment of immune-related adverse events caused by immune-checkpoint inhibitors. Cortisol, the main endogenous glucocorticoid in humans, is secreted by the adrenal cortex in response to stress. Additionally, cortisol and its inactive metabolite cortisone can be interconverted to further modulate tissue-dependent glucocorticoid action. In the past 5 years, intratumoural production of glucocorticoids, by both immune and tumour cells, has been shown to support tumour immune evasion. Here, we summarize current progress at the crossroads of endocrinology and immuno-oncology. We outline the known effects of steroid hormones on different immune cell types with a focus on glucocorticoids and androgens. We conclude with options for pharmaceutical intervention, including the engineering of cell-based therapies that resist the immunosuppressive action of steroid hormones. Overall, local steroid production and metabolism are emerging elements of tumour immune suppression that are potentially amenable to therapeutic intervention. Targeting steroid hormones to enhance anticancer therapies could increase their efficacy but will require expertise in endocrine care.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"90 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695426","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
Mitigating the environmental effects of healthcare: the role of the endocrinologist
IF 40.5 1区 医学
Nature Reviews Endocrinology Pub Date : 2025-03-13 DOI: 10.1038/s41574-025-01098-9
Chantelle Rizan, Jeanette M. Rotchell, Pei Chia Eng, Bernard Robaire, Corina Ciocan, Nitin Kapoor, Sanjay Kalra, Jodi D. Sherman
{"title":"Mitigating the environmental effects of healthcare: the role of the endocrinologist","authors":"Chantelle Rizan, Jeanette M. Rotchell, Pei Chia Eng, Bernard Robaire, Corina Ciocan, Nitin Kapoor, Sanjay Kalra, Jodi D. Sherman","doi":"10.1038/s41574-025-01098-9","DOIUrl":"https://doi.org/10.1038/s41574-025-01098-9","url":null,"abstract":"<p>Human health depends on planetary health, and yet healthcare provision can have unintended consequences for the health of the planet. Emissions from the healthcare sector include greenhouse gases, air pollution and plastic pollution, alongside chemical contamination. Chemical pollution resulting in endocrine disruption has been associated with plastics, which are a source of concerning additives such as phthalates, bisphenols, perfluoroalkyl and polyfluoroalkyl substances, and flame retardants (all routinely found in healthcare products). Many endocrine-disrupting chemicals are persistent and ubiquitous in the environment (including water and food sources), with potential secondary harms for human health, including disrupting reproductive, metabolic and thyroid function. Here we review evidence-based strategies for mitigating environmental effects of healthcare delivery. We focus on what endocrinologists can do, including reducing demand for healthcare services through better preventative health, focusing on high-value care and improving sustainability of medical equipment and pharmaceuticals through adopting circular economy principles (including reduce, reuse and, as a last resort, recycle). The specific issue of endocrine-disrupting chemicals might be mitigated through responsible disposal and processing, alongside advocating for the use of alternative materials and replacing additive chemicals with those that have lower toxicity profiles, as well as tighter regulations. We must work to urgently transition to sustainable models of care provision, minimizing negative effects on human and planetary health.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"13 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607972","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
Adrenocortical stem cells in health and disease
IF 40.5 1区 医学
Nature Reviews Endocrinology Pub Date : 2025-03-10 DOI: 10.1038/s41574-025-01091-2
Yulan Chu, Jordan Setayesh, Typhanie Dumontet, Lauren Krumeich, Johanna Werner, Isabele F. Moretti, Kelly De Sousa, Christopher Kennedy, Christopher La Pensee, Antonio M. Lerario, Gary D. Hammer
{"title":"Adrenocortical stem cells in health and disease","authors":"Yulan Chu, Jordan Setayesh, Typhanie Dumontet, Lauren Krumeich, Johanna Werner, Isabele F. Moretti, Kelly De Sousa, Christopher Kennedy, Christopher La Pensee, Antonio M. Lerario, Gary D. Hammer","doi":"10.1038/s41574-025-01091-2","DOIUrl":"https://doi.org/10.1038/s41574-025-01091-2","url":null,"abstract":"<p>The adrenal cortex is the major site of production of steroid hormones, which are essential for life. The normal development and homeostatic renewal of the adrenal cortex depend on capsular stem cells and cortical progenitor cells. These cell populations are highly plastic and support adaptation to physiological demands, injury and disease, linking steroid production and adrenal (organ) homeostasis with systemic endocrine cues and organismal homeostasis. This Review integrates findings from the past decade, outlining the mechanisms that govern the establishment and maintenance of the adrenal stem cell niche under different physiological and pathological conditions. The sophisticated regulation of the stem cell niche by gene regulatory networks, coordinated through paracrine and endocrine signalling, is highlighted in a context-dependent and sex-specific manner. We discuss how dysregulation of this intricate regulatory network is implicated in a wide range of adrenal diseases, and how emerging knowledge from adrenal stem cell research is inspiring the future development of gene-based and cell-based therapeutic strategies.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"83 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583102","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
Leptin–thyroid hormone axis affects energy use in muscle 瘦素-甲状腺激素轴影响肌肉的能量利用
IF 40.5 1区 医学
Nature Reviews Endocrinology Pub Date : 2025-03-10 DOI: 10.1038/s41574-025-01103-1
Claire Greenhill
{"title":"Leptin–thyroid hormone axis affects energy use in muscle","authors":"Claire Greenhill","doi":"10.1038/s41574-025-01103-1","DOIUrl":"https://doi.org/10.1038/s41574-025-01103-1","url":null,"abstract":"<p>Thyroid hormones have a wide range of functions, including regulating energy metabolism. In a study published in <i>Cell Metabolism</i>, a group of researchers show that leptin is involved in thyroid hormone activation, which results in an increased metabolic rate in the context of obesity.</p><p>In mice, leptin injection increased the expression of type 2 deiodinase mRNA. Of note, this effect was not seen in <i>db/db</i> mice, which lack the leptin receptor. Leptin injection also increased intramuscular levels of triiodothyronine in wild-type mice, but not in <i>db/db</i> mice. Systemic levels of thyroid hormones were not changed following leptin injection, which indicates that the hypothalamus–pituitary–thyroid axis was not affected by leptin treatment. The authors also demonstrated that leptin alters type 2 deiodinase expression via a mechanism that is dependent on STAT3 and α-MSH.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"18 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582821","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
Islet hormones at the intersection of glucose and amino acid metabolism
IF 40.5 1区 医学
Nature Reviews Endocrinology Pub Date : 2025-03-07 DOI: 10.1038/s41574-025-01100-4
Phillip J. White, Nicolai J. Wewer Albrechtsen, Jonathan E. Campbell
{"title":"Islet hormones at the intersection of glucose and amino acid metabolism","authors":"Phillip J. White, Nicolai J. Wewer Albrechtsen, Jonathan E. Campbell","doi":"10.1038/s41574-025-01100-4","DOIUrl":"https://doi.org/10.1038/s41574-025-01100-4","url":null,"abstract":"<p>The pancreatic islets of Langerhans are central to fine-tuning metabolism to ensure metabolic homeostasis during the transition between fasting and feeding. Insulin and glucagon, the principal hormones generated and secreted by islets, exert powerful control in various metabolic tissues to drive nutrient uptake, storage and metabolism. Their canonical actions on glycaemia have positioned these hormones in opposition, however, their metabolic actions extend beyond controlling blood levels of glucose. Indeed, these islet hormones are just as influential in regulating lipid and amino acid metabolism and it is becoming clear that many of these actions involve an interplay between insulin and glucagon, which is contrary to the dogmatic view that these hormones are antagonistic in nature. Finally, we postulate that examining the effects of islet hormones on the metabolism of individual metabolites is overly simplistic. Here, we discuss the actions of each islet hormone alone and in combination with the others in regulating glucose and amino acid metabolism and explore how these signalling networks are closely linked and strongly influence one another.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"63 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569468","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
How the WHIMS clinical trial shaped the future of women’s health research
IF 40.5 1区 医学
Nature Reviews Endocrinology Pub Date : 2025-03-05 DOI: 10.1038/s41574-025-01101-3
Phaedra R. Keller-Norrell
{"title":"How the WHIMS clinical trial shaped the future of women’s health research","authors":"Phaedra R. Keller-Norrell","doi":"10.1038/s41574-025-01101-3","DOIUrl":"https://doi.org/10.1038/s41574-025-01101-3","url":null,"abstract":"<p>In 1993, the 103<sup>rd</sup> United States Congress signed the NIH Revitalization Act into law; prior to this date, women (and members of minority groups) were largely excluded from clinical trials. To this day, women experience more adverse reactions to medication and surgical complications involving medical device implants than men, as the studies regarding the safety and efficacy of medications and devices have largely been conducted in men.</p><p>It was not until the early 2000s that women’s health research truly began to gain momentum in the USA, driven in part by an increase in the prevalence of sex-biased diseases, such as Alzheimer disease. Globally, women account for two-thirds of the current population of patients with Alzheimer disease; however, the mechanism underlying the susceptibility of women to Alzheimer disease remains unclear and is likely to be multifactorial. Numerous high-profile studies, the most notable being the Women’s Health Initiative Memory Study (WHIMS), have begun to investigate the role of female sex hormones in this disease.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"1 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545926","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
Anti-PIT1 hypophysitis after immune checkpoint inhibitor treatment 免疫检查点抑制剂治疗后的抗 PIT1 下丘脑炎
IF 40.5 1区 医学
Nature Reviews Endocrinology Pub Date : 2025-02-27 DOI: 10.1038/s41574-025-01099-8
Shin Urai, Genzo Iguchi, Yutaka Takahashi
{"title":"Anti-PIT1 hypophysitis after immune checkpoint inhibitor treatment","authors":"Shin Urai, Genzo Iguchi, Yutaka Takahashi","doi":"10.1038/s41574-025-01099-8","DOIUrl":"https://doi.org/10.1038/s41574-025-01099-8","url":null,"abstract":"Anti-PIT1 hypophysitis is a form of paraneoplastic autoimmune hypophysitis. The condition is attributable to the ectopic expression of pituitary-specific positive transcription factor 1 (PIT1) in tumour tissues, which leads to autoimmunity against PIT1-positive anterior pituitary cells. In the past few years, it has been reported that anti-PIT1 hypophysitis can occur as an immune checkpoint inhibitor-related hypophysitis.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"28 4 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506788","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
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