Journal of Endocrinology最新文献

{"title":"GLP-1R/NPY2R regulate gene expression, ovarian and adrenal morphology in HFD mice.","authors":"Dawood Khan, Ananyaa Sridhar, Charlotte R Moffett","doi":"10.1530/JOE-24-0189","DOIUrl":"10.1530/JOE-24-0189","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y receptors (NPYRs) are expressed in reproductive tissues contributing to the regulation of gonadal function. This exploratory study examines the potential impact of their modulation by assessing the effects of exendin-4 (Ex-4) and peptide YY (PYY) (3-36) on endocrine ovaries and adrenals in high-fat diet (HFD) mice. Ex-4 and PYY(3-36) reduced blood glucose and energy intake, with no effects on body weight. While HFD did not impact the estrous cycle, Ex-4 increased metestrus frequency and decreased diestrus frequency resulting in 0% mice experiencing repeated diestrus or becoming acyclic. Luteinizing hormone levels were significantly higher in the Ex-4 and PYY(3-36) groups compared to the normal diet and HFD controls. In the adrenals, reduced capsule and zona glomerulosa thickness caused by HFD was reversed after peptide treatments. Within the ovaries, HFD increased the number of atretic follicles, an effect that disappeared after Ex-4 and PYY(3-36) treatments. Ex-4 also increased the number of corpora lutea owing to the prolonged metestrus phase. Gene expression analysis within the adrenals revealed the upregulation of Insr and the downregulation of Prgtr in HFD mice, while Ex-4 downregulated the expression of Gipr. The ovarian gene expression of Gipr, Npy1r and Prgtr was downregulated by Ex-4 treatment, while PYY(3-36) significantly downregulated the Prgtr expression compared to HFD mice. These data indicate that manipulating GLP-1R and NPY2R leads to changes in the reproductive physiology of mice. In addition, the observed alterations in the morphology and gene expression in the adrenals and ovaries imply a direct impact of these peptides on female reproductive function.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846681","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}

{"title":"Identification of a vimentin-expressing α-cell phenotype in CF and normal pancreas.","authors":"Nicole Kattner, Yan Hang, Nicole Aj Krentz, Lydia A Russell, Matthew Palmer, Christine Flaxman, Nadine Plett, Rowan Coulthard, Yara Al-Selwi, Nicola Dyson, Minna Honkanen-Scott, Seung Kim, Dina Tiniakos, Gunter Klöppel, Sarah J Richardson, James Am Shaw","doi":"10.1530/JOE-24-0190","DOIUrl":"10.1530/JOE-24-0190","url":null,"abstract":"<p><p>Endocrine dysfunction and diabetes can develop secondary to fibrotic diseases within the pancreas including cystic fibrosis (CF). Phenotypic shift within epithelial cells has been recognised in association with pro-fibrotic signalling. We sought evidence of endocrine cell epithelial-to-mesenchymal transition in CF and non-CF pancreas. Post mortem pancreatic sections from 24 people with CF and 10 organ donors without CF or diabetes were stained for insulin/glucagon/vimentin and Sirius Red Fast Green with collagen distribution assessed semi-quantitatively (CF) and quantitatively (non-CF). Analysis of existing single-cell RNA-sequencing data sets (three adult donors without diabetes and nine with chronic pancreatitis) for α-cell vimentin expression was performed. Cells co-expressing glucagon/vimentin were detected in a proportion (32(4,61)% (median(Q1,Q3)) of islets in all CF pancreata except donors dying perinatally. CF histopathology was characterised by peri-islet fibrosis and 60(45,80)% of islets were surrounded by collagen strands. A positive correlation between islet fibrosis and vimentin-expressing α-cells was seen in non-CF donors <31 years (r=0.972, p=0.006). A possible association with donor age was seen in all donors (r=0.343, p=0.047). Single-cell RNA-sequencing analysis of isolated islets from non-diabetic donors and donors with chronic pancreatitis confirmed presence of vimentin-positive and vimentin-negative α-cells. Differentiated α-cell function-associated gene expression was maintained. Differentially upregulated processes in co-expressing cells included pathways associated with extracellular matrix organisation, cell-cell adhesion, migratory capability and self-renewal. We have identified and characterised an intermediate epithelial/mesenchymal state in a sub-population of α-cells present throughout post-natal life which may play a role in their response to extrinsic stressors including fibrosis and ageing.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006473","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}

{"title":"Leptin potentiates bone loss at skeletal sites distant from focal inflammation in female ob/ob mice.","authors":"Russell T Turner, Kenneth Philbrick, Carmen P Wong, Aidan R Fichter, Adam J Branscum, Urszula T Iwaniec","doi":"10.1530/JOE-24-0324","DOIUrl":"10.1530/JOE-24-0324","url":null,"abstract":"<p><p>Leptin increases focal inflammation and osteolysis induced by polyethylene particles in leptin-deficient ob/ob mice suggesting the adipokine, an important immune modulator, contributes to orthopedic implant failure. Focal inflammation leads to bone loss at distant skeletal sites, and it is plausible that leptin also contributes to this response. We tested this possibility in 6-week-old female ob/ob mice (6-8/group) by evaluating bone architecture, turnover, and gene expression 12 days following surgical placement of polyethylene particles over calvaria. Particle treatment had minimal effect on bone mass, density, or cancellous bone architecture in femur and 5th lumbar vertebra (LV). However, compared to controls, particle treatment altered tibial expression levels of 32/84 genes related to bone metabolism. Subcutaneous infusion of leptin (6 µg/d) to mice following placement of polyethylene particles over calvaria (combination treatment) resulted in cancellous bone loss in distal femur metaphysis and LV and in the differential expression of 34/84 genes, 15 of which overlapped with particle treatment. Notably, combination treatment, but not particle treatment, resulted in increased expression of genes strongly associated with bone turnover and response to inflammation. Leptin treatment alone (0.1-10 µg/day) did not result in bone loss in femur or LV in the ob/ob mice. These findings suggest that leptin exaggerates the detrimental effects of particle-induced inflammation on bone turnover balance, leading to systemic bone loss.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066138","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}

{"title":"Steroidogenic acute regulatory protein in fish.","authors":"Jannet Kocerha, Nancy D Denslow","doi":"10.1530/JOE-24-0232","DOIUrl":"10.1530/JOE-24-0232","url":null,"abstract":"<p><p>The importance of steroidogenesis is underscored by its vital and conserved functions from higher to lower vertebrate species, such as stress, immune, and inflammatory responses, sexual development and reproduction, osmoregulation, and even the ability to adapt to the environment and environmental changes. Correspondingly, the rate limiting step of steroidogenesis mediated by the steroidogenic acute regulatory protein is an ongoing target for scientific investigation. An expanding collection of studies have now reported key similarities, as well as some differences, in transcriptional and translational regulation of steroidogenic acute regulatory across species. This review will discuss the current understanding of steroidogenic acute regulatory in fish, as these lower vertebrate models uniquely rely on steroid hormones for osmotic balance, reproductive functions, responses to environmental stimuli, and much more.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066148","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}

{"title":"Maternal sucrose consumption alters steroid levels in the mother, placenta, and fetus.","authors":"Désirée R Seib, Minseon M Jung, Kiran K Soma","doi":"10.1530/JOE-24-0238","DOIUrl":"https://doi.org/10.1530/JOE-24-0238","url":null,"abstract":"<p><p>Maternal diet has long-term effects on offspring brain development and behavior. Sucrose (table sugar) intakes are high in modern diets, but it is not clear how a maternal high-sucrose diet (HSD) affects the offspring. In rats, a maternal HSD (26% of calories from sucrose, which is human-relevant) alters maternal metabolism and brain and also alters adult offspring endocrinology and behavior in a sex-specific manner. Maternal sucrose intake increases corticosterone levels in adult female offspring and increases motivation for a sugar reward in adult male offspring. Here, to identify possible underlying mechanisms, we examined how a maternal HSD affects steroids in the dam, placenta, and fetus at embryonic day 19.5 using liquid chromatography tandem mass spectrometry. Maternal sucrose intake increased glucocorticoids (11-deoxycorticosterone and 11-dehydrocorticosterone) and tended to increase the mineralocorticoid aldosterone in maternal serum. In the placenta, maternal sucrose intake decreased androstenedione and testosterone. Maternal HSD increased aldosterone in the fetal blood. Similarly, in the fetal brain, maternal high-sucrose intake increased aldosterone in the medial prefrontal cortex and nucleus accumbens, decreased testosterone in the nucleus accumbens, and decreased corticosterone the orbital cortex. In addition, the 11-dehydrocorticosterone/corticosterone and aldosterone/corticosterone ratios were increased in most examined brain regions. Lastly, maternal HSD increased 11-dehydrocorticosterone and aldosterone in the amniotic fluid. In summary, we found dramatic and widespread changes in maternal, placental, and fetal steroids that might mediate the long-term effects of maternal sucrose consumption on adult offspring neuroendocrinology and behavior.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052624","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}

{"title":"The levels of adropin and its therapeutic potential in diabetes.","authors":"Marek Skrzypski, Tatiana Wojciechowicz, Agnieszka Rak, Małgorzata Krążek, Joanna Fiedorowicz, Mathias Z Strowski, Krzysztof Wojciech Nowak","doi":"10.1530/JOE-24-0117","DOIUrl":"10.1530/JOE-24-0117","url":null,"abstract":"<p><p>Adropin, a peptide hormone encoded by the ENHO gene is expressed in various tissues including the brain. Accumulating evidence from in vivo and in vitro studies highlights adropin's pivotal role in modulating carbohydrate and lipid metabolism. Notably, circulating adropin levels are lower in overweight and obese humans and experimental interventions involving adropin overexpression or synthetic administration demonstrate promising outcomes in mitigating obesity-related metabolic abnormalities and preventing weight gain. This review comprehensively summarizes current understanding of adropin's potential implications in diverse types of diabetes. Specifically, it explores adropin's utility as a biomarker for different types of diabetes and elucidates its significance as a potential predictor of diabetic adverse outcomes. Furthermore, the review delves into the beneficial effects of adropin treatment in animal models of experimentally-induced diabetes, shedding light on its mechanisms of action in modulating glucose metabolism. In this comprehensive overview, we aim to provide a nuanced understanding of multifaceted role of adropin in diabetes pathogenesis and its therapeutic potential in combating this global health challenge.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064668","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}

{"title":"Continuing the success of Journal of Endocrinology and Journal of Molecular Endocrinology: Editor-in-Chief handover.","authors":"Martin Haluzik, Gabriela da Silva Xavier","doi":"10.1530/JOE-24-0305","DOIUrl":"10.1530/JOE-24-0305","url":null,"abstract":"","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"264 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872167","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}

{"title":"Glucocorticoid excess alters metabolic rate and substrate utilisation via 11β-HSD1.","authors":"Samuel R Heaselgrave, Silke Heising, Stuart A Morgan, David M Carthwright, Michael Sagmeister, Rowan S Hardy, Craig L Doig, Nicholas Morton, Kostas Tsintzas, Gareth G Lavery","doi":"10.1530/JOE-24-0205","DOIUrl":"10.1530/JOE-24-0205","url":null,"abstract":"<p><p>Systemic glucocorticoid excess causes several adverse metabolic conditions, most notably Cushing's syndrome. These effects are amplified by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Here, we determined the less well-characterised effects of glucocorticoid excess, and the contribution of 11β-HSD1 amplification on metabolic rate in mice. Male and female C57BL/6J (wild type, WT) and 11β-HSD1 knockout (11β-HSD1 KO) mice were treated with high-dose corticosterone or a vehicle control for 3 weeks. Indirect calorimetry was conducted during the final week of treatment, with or without fasting, to determine the impact on metabolic rate. We found that corticosterone treatment elevated metabolic rate and promoted carbohydrate utilisation primarily in female WT mice, with effects more pronounced during the light phase. Corticosterone treatment also resulted in greater fat accumulation in female WT mice. Corticosterone induced hyperphagia was identified as a likely causal factor altering the respiratory exchange ratio (RER) but not energy expenditure (EE). Male and female 11β-HSD1 KO mice were protected against these effects. We identify novel metabolic consequences of sustained glucocorticoid excess, identify a key mechanism of hyperphagia, and demonstrate that 11β-HSD1 is required to manifest the full metabolic derangement.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288974","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}

{"title":"GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms.","authors":"Neerav Mullur, Arianne Morissette, Nadya M Morrow, Erin E Mulvihill","doi":"10.1530/JOE-24-0046","DOIUrl":"10.1530/JOE-24-0046","url":null,"abstract":"<p><p>Cardiovascular outcome trials (CVOTs) in people living with type 2 diabetes mellitus and obesity have confirmed the cardiovascular benefits of glucagon-like peptide 1 receptor agonists (GLP-1RAs), including reduced cardiovascular mortality, lower rates of myocardial infarction, and lower rates of stroke. The cardiovascular benefits observed following GLP-1RA treatment could be secondary to improvements in glycemia, blood pressure, postprandial lipidemia, and inflammation. Yet, the GLP-1R is also expressed in the heart and vasculature, suggesting that GLP-1R agonism may impact the cardiovascular system. The emergence of GLP-1RAs combined with glucose-dependent insulinotropic polypeptide and glucagon receptor agonists has shown promising results as new weight loss medications. Dual-agonist and tri-agonist therapies have demonstrated superior outcomes in weight loss, lowered blood sugar and lipid levels, restoration of tissue function, and enhancement of overall substrate metabolism compared to using GLP-1R agonists alone. However, the precise mechanisms underlying their cardiovascular benefits remain to be fully elucidated. This review aims to summarize the findings from CVOTs of GLP-1RAs, explore the latest data on dual and tri-agonist therapies, and delve into potential mechanisms contributing to their cardioprotective effects. It also addresses current gaps in understanding and areas for further research.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982464","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}

{"title":"Aldosterone, mitochondria and regulation of cardiovascular metabolic disease.","authors":"Cheng-Hsuan Tsai, Zheng-Wei Chen, Bo-Ching Lee, Che-Wei Liao, Yi-Yao Chang, Yan-Rou Tsai, Chia-Hung Chou, Vin-Cent Wu, Chi-Sheng Hung, Yen-Hung Lin","doi":"10.1530/JOE-23-0350","DOIUrl":"10.1530/JOE-23-0350","url":null,"abstract":"<p><p>Aldosterone is a mineralocorticoid hormone involved in controlling electrolyte balance, blood pressure, and cellular signaling. It plays a pivotal role in cardiovascular and metabolic physiology. Excess aldosterone activates mineralocorticoid receptors, leading to subsequent inflammatory responses, increased oxidative stress, and tissue remodeling. Various mechanisms have been reported to link aldosterone with cardiovascular and metabolic diseases. However, mitochondria, responsible for energy generation through oxidative phosphorylation, have received less attention regarding their potential role in aldosterone-related pathogenesis. Excess aldosterone leads to mitochondrial dysfunction, and this may play a role in the development of cardiovascular and metabolic diseases. Aldosterone has the potential to affect mitochondrial structure, function, and dynamic processes, such as mitochondrial fusion and fission. In addition, aldosterone has been associated with the suppression of mitochondrial DNA, mitochondria-specific proteins, and ATP production in the myocardium through mineralocorticoid receptor, nicotinamide adenine dinucleotide phosphate oxidase, and reactive oxygen species pathways. In this review, we explore the mechanisms underlying aldosterone-induced cardiovascular and metabolic mitochondrial dysfunction, including mineralocorticoid receptor activation and subsequent inflammatory responses, as well as increased oxidative stress. Furthermore, we review potential therapeutic targets aimed at restoring mitochondrial function in the context of aldosterone-associated pathologies. Understanding these mechanisms is vital, as it offers insights into novel therapeutic strategies to mitigate the impact of aldosterone-induced mitochondrial dysfunction, thereby potentially improving the outcomes of individuals affected by cardiovascular and metabolic disorders.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909808","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}