Endocrinology最新文献

Endocrine examples of phase separation in biology. 生物学中相分离的内分泌例子。

IF 3.3 3区医学

Endocrinology Pub Date : 2025-10-23 DOI: 10.1210/endocr/bqaf158

Talia Fargason, Xu Liu

{"title":"Endocrine examples of phase separation in biology.","authors":"Talia Fargason, Xu Liu","doi":"10.1210/endocr/bqaf158","DOIUrl":"https://doi.org/10.1210/endocr/bqaf158","url":null,"abstract":"Over the past 15 years, groundbreaking discoveries have reshaped our understanding of how biomolecules are organized in space and time within cells, revealing that many cellular compartments are separated from their surroundings not by membranes, but by physical forces arising from unique interactions among their biomolecular components. These interactions drive the compartmentalization of biomolecules through liquid-liquid phase separation (LLPS) into dynamic droplets, which can further stabilize through liquid-gel phase separation (LGPS). Phase separation plays essential roles across diverse biological systems, including the endocrine system, where it impacts the function on steroid hormone receptors (SHRs). SHRs are a family of nuclear receptors that transduce steroid signals to regulate transcription of thousands of genes, thereby supporting endocrine homeostasis and contributing to diseases when dysregulated. During gene activation, SHRs form high-density clusters at promoters and enhancers. This minireview summarizes recent literature indicating that these clusters function as transcriptional condensates, where phase separation of SHRs and coregulators mediates chromatin remodeling and enhanced transcription. We also discuss hypotheses suggesting that SHR-driven LLPS at gene loci contributes to hormone therapy resistance, while a transition to LGPS causes reduced hormone responsiveness. Finally, advancements in SHR condensate-modifying drugs to create new therapeutic options for hormone therapy-resistant cancers are highlighted. Overall, emerging evidence on the phase properties of SHR condensates is transforming our understanding of the endocrine regulation and unleashing novel intervention strategies beyond targeting individual proteins.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354169","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

Split Decisions in Hormone Signaling: Distinct Roles for Progesterone Receptor Isoforms in Breast Cancer Biology. 激素信号传导中的分裂决定：孕激素受体异构体在乳腺癌生物学中的独特作用。

IF 3.3 3区医学

Endocrinology Pub Date : 2025-10-23 DOI: 10.1210/endocr/bqaf155

Noelle E Gillis, Susan I Schmidt, Carol A Lange

{"title":"Split Decisions in Hormone Signaling: Distinct Roles for Progesterone Receptor Isoforms in Breast Cancer Biology.","authors":"Noelle E Gillis, Susan I Schmidt, Carol A Lange","doi":"10.1210/endocr/bqaf155","DOIUrl":"https://doi.org/10.1210/endocr/bqaf155","url":null,"abstract":"The progesterone receptor (PR) is a critical regulator of hormone signaling in breast tissue, with its two primary isoforms, PR-A and PR-B, exhibiting distinct and sometimes opposing functions. These isoforms arise from alternative promoter usage within the PGR gene, resulting in structural differences that influence their transcriptional activity, regulatory interactions, and post-translational modifications. While PR-B is a potent transcriptional activator, PR-A can act as a dominant repressor, modulating the activity of PR-B, estrogen receptor-alpha (ER), and other nuclear receptors. This review explores the historical discovery of PR isoforms, their structural and functional differences, and the molecular mechanisms governing their transcriptional regulation. We also discuss their physiological roles in normal mammary gland development and how their dysregulation contributes to breast cancer progression, endocrine resistance, and cancer stem cell expansion. Understanding the distinct roles of PR isoforms in breast cancer biology holds significant implications for developing targeted therapeutic strategies aimed at modulating isoform-specific PR activity in hormone-driven cancers.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344429","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

Thyroid Hormone Receptor Beta Suppresses Cancer Cell Activity by Differential Regulation of Glycogen Metabolism. 甲状腺激素受体β通过糖原代谢的差异调节抑制癌细胞活性。

IF 3.3 3区医学

Endocrinology Pub Date : 2025-10-23 DOI: 10.1210/endocr/bqaf156

Justin M Zielinski, Jennifer A Tomczak, Eyal Amiel, Frances E Carr

{"title":"Thyroid Hormone Receptor Beta Suppresses Cancer Cell Activity by Differential Regulation of Glycogen Metabolism.","authors":"Justin M Zielinski, Jennifer A Tomczak, Eyal Amiel, Frances E Carr","doi":"10.1210/endocr/bqaf156","DOIUrl":"https://doi.org/10.1210/endocr/bqaf156","url":null,"abstract":"Anaplastic thyroid cancer (ATC) is one of the most lethal endocrine cancers with no enduring therapies. Thyroid hormone receptor beta (TRβ), a recognized tumor suppressor, modulates the transcriptome altering gene expression in numerous intracellular signaling pathways. Our recent studies revealed that TRβ agonism inhibits glycogen metabolism in ATC cells. Our goal in the present study was to delineate the molecular mechanisms by which TRβ regulates glycogen synthesis and breakdown. In ATC cells, activation of TRβ induced changes in expression of genes and proteins in glycogen signaling concordant with downregulation of cancer metabolism. The impact on the cancer cell metabolic phenotype was determined by glycogen levels, cell viability, and reactive oxygen species (ROS) characterization. Our results revealed that TRβ activation differentially regulates glycogen signaling pathways reflective of the genetic landscape of the cells. This suggests TRβ can suppress tumor growth and progression through multiple steps in glycogen metabolism, giving it a unique and distinct role in fine-tuning the microenvironment of the cell as an internal sensor of the general environment of the cell. These studies reveal the potential of synergistic impact of TRβ agonism and inhibition of glycogen metabolism in the treatment of aggressive dedifferentiated thyroid cancers.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354170","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

NPFFR2 Deletion Improves Hypothalamic Insulin Sensitivity and Metabolic Outcomes in Mice with Diet-Induced Obesity. NPFFR2缺失改善饮食性肥胖小鼠下丘脑胰岛素敏感性和代谢结果

IF 3.3 3区医学

Endocrinology Pub Date : 2025-10-22 DOI: 10.1210/endocr/bqaf157

Hsiang-Ting Hsu, Chun-Chun Hsu, Sze-Chi Tsai, Jin-Chung Chen, Hui-Yun Li, Ya-Tin Lin

{"title":"NPFFR2 Deletion Improves Hypothalamic Insulin Sensitivity and Metabolic Outcomes in Mice with Diet-Induced Obesity.","authors":"Hsiang-Ting Hsu, Chun-Chun Hsu, Sze-Chi Tsai, Jin-Chung Chen, Hui-Yun Li, Ya-Tin Lin","doi":"10.1210/endocr/bqaf157","DOIUrl":"https://doi.org/10.1210/endocr/bqaf157","url":null,"abstract":"Neuropeptide FF receptor 2 (NPFFR2) is a key regulator of energy homeostasis, influencing feeding behavior, insulin sensitivity, and lipid metabolism. This study investigates the metabolic consequences of Npffr2 deletion in a mouse model of diet-induced obesity. Wild-type and Npffr2 knockout mice were fed a high-fat high-sucrose diet to induce obesity, followed by comprehensive metabolic assessments. Npffr2 knockout mice exhibited reduced food intake, accompanied by significant downregulation of hypothalamic orexigenic neuropeptides agouti-related peptide and neuropeptide Y. Enhanced energy expenditure was observed in knockout mice, as evidenced by increased thermogenic capacity, elevated uncoupling protein 1 expression in brown adipose tissue, and improved core temperature maintenance under cold exposure. Lipid metabolism was also improved, with reduced hepatic and adipose lipid accumulation and lower circulating triglyceride and non-esterified fatty acid levels. Molecular analyses revealed increased AKT phosphorylation in the hypothalamus and skeletal muscle, along with downregulation of protein tyrosine phosphatase 1B in the mediobasal hypothalamus, indicating improved central and peripheral insulin signaling. Here, we demonstrated that NPFFR2 plays a critical role in obesity-associated energy regulation, lipid accumulation, and insulin resistance. These findings highlight NPFFR2 as a potential therapeutic target for obesity and related metabolic disorders.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344264","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

The multifaceted roles of pituitary pericytes in health and disease. 垂体周细胞在健康和疾病中的多方面作用。

IF 3.3 3区医学

Endocrinology Pub Date : 2025-10-21 DOI: 10.1210/endocr/bqaf152

Xiaoxue Chen, Xiaoan Ke, Yixin Lu, Hui Miao, Lian Duan, Hongbo Yang, Hui Pan, Fengying Gong, Linjie Wang, Huijuan Zhu

{"title":"The multifaceted roles of pituitary pericytes in health and disease.","authors":"Xiaoxue Chen, Xiaoan Ke, Yixin Lu, Hui Miao, Lian Duan, Hongbo Yang, Hui Pan, Fengying Gong, Linjie Wang, Huijuan Zhu","doi":"10.1210/endocr/bqaf152","DOIUrl":"https://doi.org/10.1210/endocr/bqaf152","url":null,"abstract":"Pericytes are mural cells distributed in the basement membrane of precapillary arterioles, capillaries and postcapillary venules and are indispensable parts of the vascular microenvironment. To date, pericytes have been found to play a crucial role in vascular homeostasis in several organs. The pituitary gland has a complex network of blood vessels that support endocrine function; thus, pericytes also have irreplaceable functions in the pituitary vascular microenvironment, including angiogenesis, vascular regulation, neuroendocrine, extracellular matrix regulation, and mesenchymal-like differentiation potential. Notably, emerging evidence suggests potential functional heterogeneity between anterior and posterior pituitary pericytes, which may underlie their specialized roles in regulating lobe-specific vascular and neuroendocrine activities. Additionally, the underlying impact of pericytes on pituitary lesions, such as tumors, apoplexy and fibrosis, has been revealed in the past decade. In this review, we introduce the fundamental characteristics of pituitary pericytes on the basis of their morphological characteristics, molecular markers and origin, emphasize their multiple functions under physiological conditions, and explore their latent role in pituitary diseases. This review is the first to provide a comprehensive overview of the physiological functions and pathological mechanisms of pituitary pericytes, in an attempt to develop new ideas for future research.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336713","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

Collaborative Cross Mice Provide New Insights About Vitamin D. 协作杂交小鼠提供关于维生素D的新见解。

IF 3.3 3区医学

Endocrinology Pub Date : 2025-10-14 DOI: 10.1210/endocr/bqaf153

Robert D Blank

引用次数: 0

Osmolarity controls oscillatory calcium signaling to reduce autonomous aldosterone production in zona glomerulosa cells. 渗透压控制振荡钙信号，以减少肾小球带细胞自主醛固酮的产生。

IF 3.3 3区医学

Endocrinology Pub Date : 2025-10-14 DOI: 10.1210/endocr/bqaf147

Mohamed Diagne, Molly R Gerding, David T Breault, Edward H Nieh, Mark P Beenhakker, Paula Q Barrett, Nick A Guagliardo

{"title":"Osmolarity controls oscillatory calcium signaling to reduce autonomous aldosterone production in zona glomerulosa cells.","authors":"Mohamed Diagne, Molly R Gerding, David T Breault, Edward H Nieh, Mark P Beenhakker, Paula Q Barrett, Nick A Guagliardo","doi":"10.1210/endocr/bqaf147","DOIUrl":"https://doi.org/10.1210/endocr/bqaf147","url":null,"abstract":"Primary hyperaldosteronism (PA) is characterized by autonomous aldosterone (Aldo) production, resulting in blood volume/electrolyte imbalance and hypertension. Intracellular calcium (Ca2+) is the principal signal driving Aldo synthesis in adrenal zona glomerulosa (zG) cells, and mutations in ion transport genes that regulate Ca2+ are frequently mediators of PA. When organized in intact rosette structures, zG cells are voltage oscillators; stimulation by Angiotensin II (AngII) or loss of TWIK-Related Acid-Sensitive potassium (TASK) channel function evokes stereotypic Ca²⁺ oscillations with bursting activity proportional to increased steroidogenesis. Here, we delineate the role of the osmolar-volume regulatory axis in the control of Ca2+ and Aldo production in adrenal slices. Strikingly, in both pharmacological and genetic models of PA, extracellular osmolarity (OSMEC) potently and reversibly regulated Aldo secretion and Ca²⁺ signaling. Elevated OSMEC progressively suppressed Aldo production from Angll-stimulated adrenal slices and strongly inhibited autonomous production in both zG-specific TASK knockout slices and wild-type slices incubated with TASK inhibitors. To determine if the effects of OSMEC on Ca²⁺ dynamics were causative, we imaged adrenal slices expressing zG-specific GCaMP6f incubated in variable osmotic media with TASK Inhibitors or AngII. Consistent with Aldo suppression, increasing osmolarity proportionally reduced the number of active cells and the Ca²⁺ activity of bursting cells evoked by TASK loss-of-function or AngII stimulation. Collectively, our findings identify OSMEC as a broad regulator of zG excitability and adrenal steroidogenesis, and suggest that targeting volume-regulatory mechanisms such as the Na+-K+-2Cl- cotransporter may offer a novel strategy to suppress Aldo autonomy in PA.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299352","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

Arginine vasopressin exerts opposing effects on milk ejection via oxytocin and vasopressin V1a receptors in mice. 精氨酸抗利尿激素通过催产素和抗利尿激素V1a受体在小鼠泌乳中发挥相反的作用。

IF 3.3 3区医学

Endocrinology Pub Date : 2025-10-14 DOI: 10.1210/endocr/bqaf151

Akihiro Kamikawa

{"title":"Arginine vasopressin exerts opposing effects on milk ejection via oxytocin and vasopressin V1a receptors in mice.","authors":"Akihiro Kamikawa","doi":"10.1210/endocr/bqaf151","DOIUrl":"https://doi.org/10.1210/endocr/bqaf151","url":null,"abstract":"Milk ejection is the final process in maternal milk transfer from mothers to offspring and is regulated by oxytocin (OT) released from the neurohypophysis in response to the milk ejection reflex. Arginine vasopressin (AVP), another neurohypophyseal hormone well known for its antidiuretic and vasoconstrictive effects, shares structural similarity with OT, and intravenous AVP injection can also induce milk ejection. Nonetheless, AVP has also been reported to inhibit OT-induced milk ejection in rabbits. In this study, we examined the roles of OT and AVP receptors in these opposing effects of AVP on milk ejection using an in vivo assay model in mice. AVP induced milk ejection and this effect was inhibited by an OT receptor antagonist. Intravenous pretreatment with AVP suppressed the following transient milk ejection induced by intravenous OT injection. Furthermore, AVP treatment interrupted the continuous milk ejection induced by intraperitoneal OT. These inhibitory effects of AVP were ameliorated by pretreatment with a selective Avpr1a antagonist. We further examined the role of AVP receptors using Avpr1a and Avpr1b knockout mice. The AVP-dependent inhibition of OT-induced milk ejection was abolished in Avpr1a knockout mice, but not in Avpr1b knockout mice. Our findings suggest that AVP induces milk ejection through the OT receptor while inhibiting OT-induced milk ejection via Avpr1a. This duality might reflect a physiological mechanism for restricting milk transfer under severe stress or hyperosmotic conditions and could provide insights into breastfeeding difficulties in humans, including the perception of insufficient milk and infant failure to thrive.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285829","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

Liquid Crystal Monomers and Their Mixtures Alter Nuclear Receptor Signaling and Promote Adipogenesis In Vitro. 液晶单体及其混合物改变核受体信号并促进体外脂肪形成。

IF 3.3 3区医学

Endocrinology Pub Date : 2025-10-09 DOI: 10.1210/endocr/bqaf143

Samantha M Heldman, Kristin M Eccles, Christopher D Kassotis

{"title":"Liquid Crystal Monomers and Their Mixtures Alter Nuclear Receptor Signaling and Promote Adipogenesis In Vitro.","authors":"Samantha M Heldman, Kristin M Eccles, Christopher D Kassotis","doi":"10.1210/endocr/bqaf143","DOIUrl":"10.1210/endocr/bqaf143","url":null,"abstract":"Liquid crystal monomers (LCMs) are ubiquitous environmental contaminants released from electronic devices' liquid crystal display (LCD) panels, which have led to the contamination of food, breast milk, and serum. As the toxicity of individual LCMs, not to mention their myriad mixtures, is currently very poorly characterized, there is a crucial need for investigations into the health hazards posed by exposure. In this study, 10 nonfluorinated (NF) and fluorinated (F) LCMs and 3 fluorination-based LCM mixtures were screened for metabolism and endocrine-disrupting potential in vitro at exposure-relevant concentrations using adipogenesis assays and luciferase reporter gene assays. Both NF-LCMs, F-LCMs, and their mixtures were found to alter the transcriptional activity of one or more nuclear receptors. Notably, 6 LCMs and all LCM mixtures were able to antagonize the progesterone receptor, with several displaying non-monotonic concentration-response curves. Multiple LCMs and their mixtures also increased triglyceride accumulation in murine preadipocytes and human mesenchymal stem cells in a concentration-dependent manner. The concentration addition principle underestimated the adipogenic potencies of LCM mixtures when compared with those derived from benchmark concentration analyses of empirical adipogenesis assay results, suggesting synergistic interactions. While no mechanistic pattern emerged between the bioactivities, results confirmed the metabolism and endocrine-disrupting potential of both NF-LCMs, F-LCMs, and their mixtures. This emphasizes the need to further investigate the metabolic and reproductive health impacts of LCM exposure in vivo, as well as the necessity of exploring alternative models to predict the toxicity of LCM mixtures.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136905","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

Biological Mechanisms Balancing Torpor and Reproduction in Mammals. 哺乳动物冬眠与繁殖平衡的生物学机制。

IF 3.3 3区医学

Endocrinology Pub Date : 2025-10-09 DOI: 10.1210/endocr/bqaf141

Paul B Vander, Stephanie M Correa

引用次数: 0