Current Opinion in Endocrine and Metabolic Research最新文献

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Disparities in endocrine-disrupting chemical exposures and thyroid disorders 内分泌干扰化学物质暴露与甲状腺疾病的差异

Current Opinion in Endocrine and Metabolic Research

Pub Date : 2025-12-01 DOI: 10.1016/j.coemr.2025.100591

Luyu Wang , Jennifer Flores , Robert M. Sargis

Over the last twenty years, thyroid disorder prevalence has more than doubled in the United States, with notable disparities emerging in disease incidence and outcomes. While partially attributable to inequities in healthcare delivery, whether environmental factors such as exposure to endocrine-disrupting chemicals (EDCs) contribute to differences in thyroid disease pathogenesis in vulnerable populations is plausible but understudied. To better understand how environmental factors may contribute to thyroid disease disparities, this review discusses differences in exposure to several thyroid-disrupting EDCs among historically disadvantaged communities, including polychlorinated biphenyls, bisphenols, brominated flame retardants, organochlorine pesticides, phthalates, per-/polyfluoroalkyl substances, and non-ess metals. Coupled with knowledge of exposure sources, these data may empower individual- and policy-level interventions to address thyroid disease disparities and promote health equity.

在过去的二十年中，甲状腺疾病的患病率在美国增加了一倍多，在疾病发病率和结果方面出现了显著的差异。虽然部分归因于医疗保健服务的不公平，但环境因素（如暴露于内分泌干扰化学物质（EDCs））是否导致脆弱人群甲状腺疾病发病机制的差异似乎是合理的，但尚未得到充分研究。为了更好地了解环境因素如何导致甲状腺疾病的差异，本综述讨论了在历史上处于不利地位的社区中暴露于几种干扰甲状腺的EDCs的差异，包括多氯联苯、双酚、溴化阻燃剂、有机氯农药、邻苯二甲酸盐、全氟/多氟烷基物质和非金属。再加上对暴露源的了解，这些数据可以增强个人和政策层面的干预措施，以解决甲状腺疾病的差异并促进卫生公平。

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Cholesterol metabolism and oxysterols in neurodegenerative disorders: Spotlight on Alzheimer's disease 神经退行性疾病中的胆固醇代谢和氧甾醇：聚焦于阿尔茨海默病

Current Opinion in Endocrine and Metabolic Research

Pub Date : 2025-10-16 DOI: 10.1016/j.coemr.2025.100590

Ljerka Delac , Silvia Maioli

Cholesterol metabolism in the brain is tightly regulated and differs from the periphery due to the blood–brain barrier (BBB). Oxysterols, oxidized cholesterol metabolites, can cross the BBB and play key roles in brain cholesterol homeostasis and neurodegeneration, particularly in Alzheimer's disease (AD). This review highlights two major oxysterols: brain-derived 24S-hydroxycholesterol (24-OH) and peripherally derived 27-hydroxycholesterol (27-OH). Both have been studied as potential AD biomarkers, with altered levels observed in cerebrospinal fluid and plasma, though findings vary due to sex, age, and comorbidities. Animal studies suggest that CYP46A1 and its product 24-OH support cognitive function, reduce neuroinflammation, and attenuate AD pathology, especially in females. Conversely, increased 27-OH is linked to metabolic dysfunction, synaptic deficits, and memory loss, possibly bridging peripheral hypercholesterolemia and AD risk. This review summarizes recent advances in oxysterol research and their implications for AD, emphasizing sex-specific effects and their potential as biomarkers and therapeutic targets.

由于血脑屏障（BBB），大脑中的胆固醇代谢受到严格调节，与外周不同。氧化胆固醇代谢物氧化甾醇可以穿过血脑屏障，在脑胆固醇稳态和神经变性中发挥关键作用，特别是在阿尔茨海默病（AD）中。本文综述了两种主要的氧甾醇：脑源性24s -羟基胆固醇（24-OH）和外周性27-羟基胆固醇（27-OH）。两者都作为潜在的阿尔茨海默病生物标志物进行了研究，在脑脊液和血浆中观察到水平改变，尽管结果因性别、年龄和合并症而异。动物研究表明CYP46A1及其产物24-OH支持认知功能，减少神经炎症，减轻AD病理，尤其是在女性中。相反，27-OH的增加与代谢功能障碍、突触缺陷和记忆丧失有关，可能是外周高胆固醇血症和AD风险的桥梁。本文综述了近年来羟甾醇的研究进展及其对阿尔茨海默病的影响，强调了其性别特异性作用及其作为生物标志物和治疗靶点的潜力。

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Advances in medical and surgical therapies for transgender and gender-diverse individuals 跨性别者和性别多样化个体的医疗和外科治疗进展

Current Opinion in Endocrine and Metabolic Research

Pub Date : 2025-09-30 DOI: 10.1016/j.coemr.2025.100588

Aaron L. Misakian , Maja Marinkovic

This review aims to highlight new advances in transgender medicine, including innovative approaches to pubertal and menstrual suppression, gender-affirming hormone therapy, and management of voice dysphoria for both adolescent and adult patients.

本文综述了跨性别医学的新进展，包括青春期和月经抑制的创新方法，性别肯定激素治疗，以及青少年和成人患者声音不安的管理。

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Perchlorate and thyroid function 高氯酸盐和甲状腺功能

Current Opinion in Endocrine and Metabolic Research

Pub Date : 2025-09-27 DOI: 10.1016/j.coemr.2025.100589

Stacy N. Handler, Maria A. Luna Cuadros, Elizabeth N. Pearce

Perchlorate is an environmental contaminant found around the world. Perchlorate disrupts thyroid function by inhibiting the sodium iodide symporter, which transports iodide into the thyroid. The impact of perchlorate on thyroid function is of particular concern during gestation. This review focuses on human studies related to the thyroidal effects of perchlorate. Some of the earliest human studies of perchlorate and thyroid function studied high-dose exposure through randomized control trials and occupational studies. These gave way to epidemiologic and cohort studies focusing on environmental exposures. The results of these studies have been variable but suggest that high levels of environmental perchlorate exposure, particularly in the setting of iodine deficiency, may impair thyroid function and fetal neurological development. Regulatory efforts have been supported by the advent of biologically dose-dependent response models. Understanding this body of the literature is critical for developing policies aimed at regulating perchlorate exposures and protecting society’s most vulnerable populations.

高氯酸盐是一种世界各地都存在的环境污染物。高氯酸盐通过抑制碘化钠同向转运体来破坏甲状腺功能，碘化钠同向转运体将碘化物运送到甲状腺。高氯酸盐对妊娠期甲状腺功能的影响尤其值得关注。本文综述了高氯酸盐对甲状腺功能的人体研究。一些关于高氯酸盐和甲状腺功能的早期人体研究是通过随机对照试验和职业研究来研究高剂量暴露的。这些让位于关注环境暴露的流行病学和队列研究。这些研究的结果各不相同，但表明高水平的环境高氯酸盐暴露，特别是在碘缺乏的情况下，可能损害甲状腺功能和胎儿神经发育。生物剂量依赖性反应模型的出现为监管工作提供了支持。理解这些文献对于制定旨在调节高氯酸盐暴露和保护社会最弱势群体的政策至关重要。

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Endocrine disruptive chemicals (EDCs) and autoimmune thyroid diseases (AITD): A systematic literature review 内分泌干扰物（EDCs）与自身免疫性甲状腺疾病（AITD）：系统的文献综述

Current Opinion in Endocrine and Metabolic Research

Pub Date : 2025-09-03 DOI: 10.1016/j.coemr.2025.100585

Mathilda Monaghan , Sonia Rodrigues , Shiven Sharma , Angela M. Leung , Maaike van Gerwen

The association between endocrine disruptive chemicals (EDCs) and autoimmune thyroid disease (AITD) has not been well established. This systematic review aimed to summarize existing literature and provide an up-to-date overview of EDCs and their association with AITD. A search of the National Library of Medicine PubMed and Scopus databases was completed to identify relevant articles published in English through September 2024. A total of 4 studies met inclusion criteria. Results of the included studies varied, ranging from significant positive to significant negative associations with AITD for different EDCs. This comprehensive review highlights the limited knowledge of this association. Besides investigating individual EDCs, it is important to include dose–response studies and exposures to EDC mixtures.

内分泌干扰化学物质（EDCs）与自身免疫性甲状腺疾病（AITD）之间的关系尚未得到很好的证实。本系统综述旨在总结现有文献，并提供最新的EDCs及其与AITD的关系综述。对美国国家医学图书馆PubMed和Scopus数据库进行检索，以确定截至2024年9月发表的相关英文文章。共有4项研究符合纳入标准。纳入的研究结果各不相同，不同EDCs与AITD的相关性从显著正相关到显著负相关不等。这篇全面的综述强调了这种关联的有限知识。除了调查个别EDC外，重要的是纳入剂量反应研究和暴露于EDC混合物。

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Editorial board page 编委会页面

Current Opinion in Endocrine and Metabolic Research

Pub Date : 2025-09-01 DOI: 10.1016/S2451-9650(25)00017-1

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Psychological outcomes of gender-affirming medical treatment in transgender youth 变性青年性别肯定医疗的心理结果

Current Opinion in Endocrine and Metabolic Research

Pub Date : 2025-07-29 DOI: 10.1016/j.coemr.2025.100584

Puja Singh , Ximena Lopez

The evaluation and management for transgender and gender-diverse (TGD) youth is multidisciplinary, and treatment involves social support, mental health care, and gender affirming medical care such as use of puberty suppression and/or gender-affirming hormone therapy (GAH). Gender-affirming medical care has been proven to improve psychosocial outcomes in TGD youth. This includes decreased rates of depression and anxiety and decreased suicidal ideation. Furthermore, youth who receive GAH have improvements in experienced body dysphoria, general well-being, and quality of life. Available studies show that rates of regret are low. The goal of this article is to highlight the most significant research on the effects of gender-affirming medical treatments on the psychosocial health of TGD youth.

对跨性别和性别多样化（TGD）青年的评估和管理是多学科的，治疗涉及社会支持、精神卫生保健和性别肯定医疗护理，如使用青春期抑制和/或性别肯定激素治疗（GAH）。性别肯定医疗保健已被证明可改善TGD青年的社会心理结果。这包括抑郁、焦虑和自杀意念的减少。此外，接受GAH治疗的青少年在经历过的身体不安、总体幸福感和生活质量方面都有所改善。现有的研究表明，后悔的比率很低。本文的目的是强调性别肯定医学治疗对TGD青年心理社会健康影响的最重要研究。

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Oxysterol-related disorders Oxysterol-related障碍

Current Opinion in Endocrine and Metabolic Research

Pub Date : 2025-06-25 DOI: 10.1016/j.coemr.2025.100583

Akira Honda , Hajime Ueda , Teruo Miyazaki , Tadashi Ikegami

Recent advances in oxysterol analysis and studies on their molecular targets indicate that oxysterols, enzymatic or non-enzymatic cholesterol derivatives, are active molecules involved in the pathophysiology of various diseases. This review describes and discusses the recent developments in several oxysterol-related disorders, including atherosclerosis, metabolic dysfunction-associated steatotic liver disease, Alzheimer’s disease, multiple sclerosis, and breast and lung cancers. Unlike congenital abnormalities of oxysterol-metabolizing enzymes, such as cerebrotendinous xanthomatosis and hereditary spastic paraplegia type 5, it is often difficult to assess whether altered oxysterol levels in acquired diseases are the cause or the consequence of disease. In addition, oxysterols exert beneficial or deleterious effects on diseases depending on their structures. Despite these limitations, accumulated experimental evidence is beginning to clarify the impact of oxysterols on the pathophysiology of various diseases.

近年来氧甾醇分析及其分子靶点的研究进展表明，氧甾醇作为酶促或非酶促胆固醇衍生物，是参与多种疾病病理生理的活性分子。这篇综述描述并讨论了几种与氧甾醇相关的疾病的最新进展，包括动脉粥样硬化、代谢功能障碍相关的脂肪变性肝病、阿尔茨海默病、多发性硬化症、乳腺癌和肺癌。与先天性的羟甾醇代谢酶异常不同，如脑腱黄瘤病和遗传性痉挛性截瘫5型，通常很难评估获得性疾病中的羟甾醇水平改变是疾病的原因还是结果。此外，氧甾醇根据其结构对疾病产生有益或有害的影响。尽管存在这些局限性，积累的实验证据开始阐明氧化甾醇对各种疾病病理生理的影响。

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25-hydroxycholesterol in inflammation 25-羟基胆固醇在炎症中的作用

Current Opinion in Endocrine and Metabolic Research

Pub Date : 2025-06-25 DOI: 10.1016/j.coemr.2025.100582

Romeo Carre, Solenne Vigne, Caroline Pot

Oxysterols, biological active oxidized forms of cholesterol, regulate cholesterol metabolism and intracellular cholesterol levels. They have been attributed additional roles during inflammation and recent data have highlighted their implication in human diseases. The oxysterol downstream of cholesterol 25-hydroxylase (Ch25h), 25-Hydroxycholesterol (25-HC), is largely produced during inflammatory processes. 25-HC and its derived oxysterols play critical roles in immune cell chemotaxis, viral replication inhibition, and neuroinflammation. Mechanistically, mitochondrial function, inflammasomes, endoplasmic reticulum stress, cell death, and cellular metabolism are involved. This review aims to bring the latest knowledge about the role of Ch25h-derived oxysterols under inflammatory conditions related to human diseases, specifically autoimmunity, neurological disorders, and cancers.

氧化甾醇是胆固醇的生物活性氧化形式，调节胆固醇代谢和细胞内胆固醇水平。它们被认为在炎症过程中起着额外的作用，最近的数据强调了它们在人类疾病中的意义。胆固醇25-羟化酶（Ch25h）下游的羟甾醇，25-羟基胆固醇（25-HC），在炎症过程中大量产生。25-HC及其衍生的氧甾醇在免疫细胞趋化、病毒复制抑制和神经炎症中发挥关键作用。机制上涉及线粒体功能、炎性小体、内质网应激、细胞死亡和细胞代谢。本文综述了ch25h衍生的氧化甾醇在与人类疾病相关的炎症条件下的作用的最新知识，特别是自身免疫、神经系统疾病和癌症。

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A revised Oxysterol Hypothesis highlighting the special roles played by 24(S),25-Epoxycholesterol 修正后的氧甾醇假说强调了24(S)，25-环氧胆固醇的特殊作用

Current Opinion in Endocrine and Metabolic Research

Pub Date : 2025-06-01 DOI: 10.1016/j.coemr.2025.100578

Nicole M. Fenton, Laura J. Sharpe, Andrew J. Brown

First proposed in 1978, the Oxysterol Hypothesis asserted that oxysterols exert feedback regulation on cholesterol synthesis rather than cholesterol itself. We argue for a revised Oxysterol Hypothesis focussing on recent findings regarding one oxysterol in particular. 24(S),25-epoxycholesterol (24,25EC) is synthesised by a shunt in the cholesterol synthesis pathway, in addition to being produced in the brain from a cholesterol precursor by a sterol hydroxylase (CYP46A1). 24,25EC is implicated in biological processes far beyond just cholesterol metabolism, including being an agonist for Smoothened which transduces the signal in the Hedgehog development pathway, and exerting profound effects on immune functions. We discuss how manipulating 24,25EC is of clinical interest in treating a wide range of disorders, including liver diseases, neurological diseases, and cancers.

1978年首次提出的“氧甾醇假说”认为，氧甾醇对胆固醇合成发挥反馈调节作用，而不是胆固醇本身。我们主张修订的羟甾醇假说，重点关注最近的发现，特别是一种羟甾醇。24(S)，25-环氧胆固醇（24,25ec）除了在大脑中由胆固醇前体通过固醇羟化酶（CYP46A1）产生外，还可通过胆固醇合成途径中的分流合成。24,25ec涉及的生物过程远不止胆固醇代谢，包括作为Smoothened的激动剂，在Hedgehog发育途径中传导信号，并对免疫功能产生深远影响。我们讨论了如何操纵24,25ec在治疗包括肝脏疾病、神经系统疾病和癌症在内的广泛疾病方面具有临床意义。

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