Journal of Endocrinology最新文献

Thirty years of StAR gazing: expanding the universe of the steroidogenic acute regulatory protein.

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-01-01 DOI: 10.1530/JOE-24-0310

Walter L Miller

{"title":"Thirty years of StAR gazing: expanding the universe of the steroidogenic acute regulatory protein.","authors":"Walter L Miller","doi":"10.1530/JOE-24-0310","DOIUrl":"https://doi.org/10.1530/JOE-24-0310","url":null,"abstract":"Current understanding of the biology, biochemistry and genetics of the steroidogenic acute regulatory protein (StAR) and its deficiency state (congenital lipoid adrenal hyperplasia, lipoid CAH) involves the complex interplay of four areas of study: the acute regulation of steroidogenesis, clinical phenomena in lipoid CAH, the enzymatic conversion of cholesterol to pregnenolone in steroidogenic mitochondria, and the cell biology of StAR. This review traces the origins of these areas of study, describes how they have been woven into an increasingly coherent fabric, and tries to explore some remaining loose ends in this ongoing field of endocrine research. Abundant research from multiple laboratories establishes that StAR is required for the rapid, abundant steroidal responses of the adrenals and gonads, but all steroidogenic cells, especially the placenta, have StAR-independent steroidogenesis, whose basis remains under investigation. Lipoid CAH is the StAR-knockout of nature whose complex (and unexpected) clinical features are explained by the 'two-hit model' in which StAR-dependent and StAR-independent steroidogenesis are sequentially lost. StAR is targeted to mitochondria and acts on the outer mitochondrial membrane before being imported via the 'translocase of outer membrane' (Tom) system, and then inactivated by mitochondrial proteases. A role for the 'translocator protein' (TSPO) has long been proposed, but an essential role for TSPO is excluded by recent transgenic mouse experiments. Crystal structures show that a StAR molecule can bind one cholesterol, but does not explain how each StAR molecule triggers the import of hundreds on cholesterol molecules; this is the most pressing area for future research.","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":"142949558","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

Cardiovascular effects of tirzepatide.

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-01-01 DOI: 10.1530/JOE-24-0259

Priya Sumithran, Anthony W Russell, Sophia Zoungas

引用次数: 0

The role of glucagon-like peptides in osteosarcopenia.

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2024-12-01 DOI: 10.1530/JOE-24-0210

Enaya Tufail, Somali Sanyal, Ambrish Mithal, Sabyasachi Sanyal, Naibedya Chattopadhyay

{"title":"The role of glucagon-like peptides in osteosarcopenia.","authors":"Enaya Tufail, Somali Sanyal, Ambrish Mithal, Sabyasachi Sanyal, Naibedya Chattopadhyay","doi":"10.1530/JOE-24-0210","DOIUrl":"https://doi.org/10.1530/JOE-24-0210","url":null,"abstract":"Various metabolic abnormalities including obesity, insulin resistance, hypertension, dyslipidemia, hyperthyroidism, and low vitamin D levels have been linked to both osteopenia and sarcopenia. Osteo-sarcopenia is also commonly observed due to aging that notably include postmenopausal women. GLP-1, a labile incretin secreted from the intestinal L-cells stimulates insulin secretion and sensitivity, making it an effective anti-diabetic medication. GLP-1 binds to its receptor, the GLP-1 receptor, a G-protein-coupled receptor, and leads to the stimulation of adenylate cyclase, increasing the levels of cyclic AMP (cAMP). Elevated cAMP then activates protein kinase A and other downstream signaling pathways. These signaling cascades result in various cellular responses, such as enhanced insulin secretion from pancreatic beta cells, improved insulin sensitivity, and modulation of appetite and gastric emptying. Additionally, GLP-1 signaling can promote cell growth and survival, contributing to its effects on muscle and bone health. Its role as an anti-diabetic medication has been enhanced through various modifications to extend its half-life, thereby improving its effectiveness and druggability. GLP-1 analogs, initially developed for diabetes management, have also been harnessed for obesity treatment due to the effect of GLP-1 to induce satiety and slow gastric emptying. Beyond their well-known anti-diabetic and anti-obesity effects, GLP-1 agonists can enhance muscle mass and bone density, making them valuable in addressing conditions like sarcopenia and osteoporosis. This review focuses on the effects of GLP-1 analogs on musculoskeletal health, by critically assessing the underlying signaling mechanisms in order to understand their translational potential for the treatment of osteo-sarcopenia.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801072","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

GLP-1R/NPY2R regulate gene expression, ovarian and adrenal morphology in HFD mice.

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2024-12-01 DOI: 10.1530/JOE-24-0189

Dawood Khan, Ananyaa Sridhar, R Charlotte Moffett

{"title":"GLP-1R/NPY2R regulate gene expression, ovarian and adrenal morphology in HFD mice.","authors":"Dawood Khan, Ananyaa Sridhar, R Charlotte Moffett","doi":"10.1530/JOE-24-0189","DOIUrl":"https://doi.org/10.1530/JOE-24-0189","url":null,"abstract":"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 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 estrous cycle, Ex-4 increased metestrus frequency and decreased diestrus frequency resulting in 0% mice experiencing repeated diestrus or becoming acyclic. LH levels were significantly higher in the Ex-4 and PYY(3-36) groups compared to ND and HFD controls. In the adrenals, reduced capsule and zona glomerulosa thickness cause 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 upregulation of Insr and downregulation of Prgtr in HFD mice, while Ex-4 downregulated the expression of Gipr. Ovarian gene expression of Gipr, Npy1r and Prgtr were downregulated by Ex-4 treatment, while PYY(3-36) significantly downregulated Prgtr expression compared to HFD mice. These data indicate that manipulating GLP-1R and NPY2R lead to changes in the reproductive physiology of mice. Additionally, 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.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The interplay between ECTO and ENDO exposomes on metabolic diseases through lifespan: exposome loop as a new concept.

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2024-12-01 DOI: 10.1530/JOE-24-0272

Leticia Rafael-Vázquez, Yazmín Godínez-Solís, Daniela Cortés-Gutiérrez, Lorena López-Griego, Esmeralda Palacios-Brito, Brenda Méndez-García, Andrea Diaz-Villaseñor

引用次数: 0

Glucocorticoid excess alters metabolic rate and substrate utilisation via 11β-HSD1. 糖皮质激素过量会通过 11β-HSD1 改变代谢率和底物利用率。

IF 4.3 3区医学

Journal of Endocrinology Pub Date : 2024-10-28 Print Date: 2024-11-01 DOI: 10.1530/JOE-24-0205

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

{"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":"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.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":4.3,"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}

引用次数: 0

GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms. GLP-1 受体激动剂与心血管风险：机制综述。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2024-09-19 Print Date: 2024-10-01 DOI: 10.1530/JOE-24-0046

Neerav Mullur, Arianne Morissette, Nadya M Morrow, Erin E Mulvihill

{"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":"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.","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}

引用次数: 0

Aldosterone, mitochondria and regulation of cardiovascular metabolic disease. 醛固酮、线粒体和心血管代谢疾病的调节。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2024-09-13 Print Date: 2024-10-01 DOI: 10.1530/JOE-23-0350

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

{"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":"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.","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}

引用次数: 0

The GHSR1a antagonist LEAP2 regulates islet hormone release in a sex-specific manner GHSR1a 拮抗剂 LEAP2 以性别特异性方式调节胰岛激素的释放

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-09-01 DOI: 10.1530/joe-24-0135

Nirun Hewawasam, Debalina Sakar, Olivia Bolton, Blerinda Delishaj, Maha Almutairi, Aileen King, Ayse S Dereli, Chloe Despontin, Patrick Gilon, Sue Reeves, Michael Patterson, Astrid Christine Hauge-Evans

{"title":"The GHSR1a antagonist LEAP2 regulates islet hormone release in a sex-specific manner","authors":"Nirun Hewawasam, Debalina Sakar, Olivia Bolton, Blerinda Delishaj, Maha Almutairi, Aileen King, Ayse S Dereli, Chloe Despontin, Patrick Gilon, Sue Reeves, Michael Patterson, Astrid Christine Hauge-Evans","doi":"10.1530/joe-24-0135","DOIUrl":"https://doi.org/10.1530/joe-24-0135","url":null,"abstract":"LEAP2, a liver-derived antagonist for the ghrelin receptor, GHSR1a, counteracts effects of ghrelin on appetite and energy balance. Less is known about its impact on blood glucose-regulating hormones from pancreatic islets. Here we investigate whether acyl-ghrelin (AG) and LEAP2 regulate islet hormone release in a cell type- and sex-specific manner. Hormone content from secretion experiments with isolated islets from male and female mice was measured by radioimmunoassay and mRNA expression by qPCR. LEAP2 enhanced insulin secretion in islets from males (p<0.01) but not females (p<0.2), whilst AG-stimulated somatostatin release was significantly reversed by LEAP2 in males (p<0.001) but not females (p<0.2). Glucagon release was not significantly affected by AG and LEAP2. Ghsr1a, Ghrelin, Leap2, Mrap2, Mboat4 and Sstr3 islet mRNA expression did not differ between sexes. In control male islets maintained without 17-beta oestradiol (E2), AG exerted an insulinostatic effect (p<0.05), with a trend towards reversal by LEAP2 (p=0.06). Both were abolished by 72h E2 pre-treatment (10 nmol/l, p<0.2). AG-stimulated somatostatin release was inhibited by LEAP2 from control (p<0.001) but not E2-treated islets (p<0.2). LEAP2 and AG did not modulate insulin secretion from MIN6 beta cells and Mrap2 was downregulated (P<0.05) and Ghsr1a upregulated (P<0.0001) in islets from Sst-/-\u0000 mice. Our findings show that AG and LEAP2 regulate insulin and somatostatin release in an opposing and sex-dependent manner, which in males can be modulated by E2. We suggest that regulation of SST release is a key starting point for understanding the role of GHSR1a in islet function and glucose metabolism.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"31 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255678","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 mineralocorticoid system, cardiometabolic health and its interplay with adipose tissue 矿皮质激素系统、心脏代谢健康及其与脂肪组织的相互作用

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-09-01 DOI: 10.1530/joe-24-0119

Moe Thuzar, Muthanna Abdul Halim, Michael Stowasser

{"title":"The mineralocorticoid system, cardiometabolic health and its interplay with adipose tissue","authors":"Moe Thuzar, Muthanna Abdul Halim, Michael Stowasser","doi":"10.1530/joe-24-0119","DOIUrl":"https://doi.org/10.1530/joe-24-0119","url":null,"abstract":"The mineralocorticoid system, comprising the renin-angiotensin-aldosterone system (RAAS) and associated receptors, is traditionally viewed as a regulator of sodium and fluid balance and blood pressure (BP), with the main mineralocorticoid hormone aldosterone acting via the mineralocorticoid receptor (MR) in distal renal tubules. Over the past few decades, there has been a wider understanding of the role of the mineralocorticoid system in regulating both classical BP-dependent and non-BP-dependent systemic effects. Mounting evidence indicates the novel role of the mineralocorticoid system in cardiometabolic health with excess mineralocorticoid system activity being associated with adiposity, diabetes, insulin resistance and cardiovascular diseases independent of its effect on BP, and RAAS blockade and MR antagonists offering protection against cardiometabolic dysfunction. The metabolic manifestations of mineralocorticoid system overactivation are mainly mediated by their interactions with adipose tissue which orchestrates energy, lipids and glucose homeostasis via effects on the functions of brown and white adipocytes and immune cells. Adipose tissue can in turn influence mineralocorticoid system activity by harbouring its own RAAS system and by releasing mineralocorticoid-secretory factors/adipokines, with resultant further progression of cardiometabolic dysfunction. This article discusses the interplay between the mineralocorticoid system and adipose tissue in the pathophysiology of cardiometabolic diseases.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"102 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255676","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