Endocrinology最新文献_第5页

Correction to: "BCAS2 Participates in Insulin Synthesis and Secretion via mRNA Alternative Splicing in Mice". 更正："小鼠 BCAS2 通过 mRNA 替代剪接参与胰岛素合成和分泌》。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae096

引用次数: 0

Thyroid Hormone Receptors in Control of Heart Rate. 控制心率的甲状腺激素受体

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae093

Riccardo Dore, Jens Mittag

引用次数: 0

High-throughput Screening for Cushing Disease: Therapeutic Potential of Thiostrepton via Cell Cycle Regulation. 库欣病的高通量筛选：硫司群通通过细胞周期调节的治疗潜力。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae089

Takuro Hakata, Ichiro Yamauchi, Daisuke Kosugi, Taku Sugawa, Haruka Fujita, Kentaro Okamoto, Yohei Ueda, Toshihito Fujii, Daisuke Taura, Nobuya Inagaki

{"title":"High-throughput Screening for Cushing Disease: Therapeutic Potential of Thiostrepton via Cell Cycle Regulation.","authors":"Takuro Hakata, Ichiro Yamauchi, Daisuke Kosugi, Taku Sugawa, Haruka Fujita, Kentaro Okamoto, Yohei Ueda, Toshihito Fujii, Daisuke Taura, Nobuya Inagaki","doi":"10.1210/endocr/bqae089","DOIUrl":"10.1210/endocr/bqae089","url":null,"abstract":"Cushing disease is a life-threatening disorder caused by autonomous secretion of ACTH from pituitary neuroendocrine tumors (PitNETs). Few drugs are indicated for inoperative Cushing disease, in particular that due to aggressive PitNETs. To explore agents that regulate ACTH-secreting PitNETs, we conducted high-throughput screening (HTS) using AtT-20, a murine pituitary tumor cell line characterized by ACTH secretion. For the HTS, we constructed a live cell-based ACTH reporter assay for high-throughput evaluation of ACTH changes. This assay was based on HEK293T cells overexpressing components of the ACTH receptor and a fluorescent cAMP biosensor, with high-throughput acquisition of fluorescence images. We treated AtT-20 cells with compounds and assessed ACTH concentrations in the conditioned media using the reporter assay. Of 2480 screened bioactive compounds, over 50% inhibition of ACTH secreted from AtT-20 cells was seen with 84 compounds at 10 μM and 20 compounds at 1 μM. Among these hit compounds, we focused on thiostrepton (TS) and determined its antitumor effects in both in vitro and in vivo xenograft models of Cushing disease. Transcriptome and flow cytometry analyses revealed that TS administration induced AtT-20 cell cycle arrest at the G2/M phase, which was mediated by FOXM1-independent mechanisms including downregulation of cyclins. Simultaneous TS administration with a cyclin-dependent kinase 4/6 inhibitor that affected the cell cycle at the G0/1 phase showed cooperative antitumor effects. Thus, TS is a promising therapeutic agent for Cushing disease. Our list of hit compounds and new mechanistic insights into TS effects serve as a valuable foundation for future research.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765788","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

Comprehensive Characterization of Islet Remodeling in Development and in Diabetes Using Mass Cytometry. 利用质谱仪全面鉴定发育过程中和糖尿病患者的胰岛重塑。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae094

Maria Pilar Toledo, Gengqiang Xie, Yue J Wang

{"title":"Comprehensive Characterization of Islet Remodeling in Development and in Diabetes Using Mass Cytometry.","authors":"Maria Pilar Toledo, Gengqiang Xie, Yue J Wang","doi":"10.1210/endocr/bqae094","DOIUrl":"10.1210/endocr/bqae094","url":null,"abstract":"The pancreatic islet is the functional and structural unit of the pancreatic endocrine portion. Islet remodeling occurs in both normal development and pathogenesis of type 1 (T1D) and type 2 diabetes (T2D). However, accurately quantifying changes in islet cellular makeup and hormone expressions poses significant challenges due to large intra- and inter-donor heterogeneity and the limited scalability of traditional methods such as immunostaining. The cytometry by time-of-flight (CyTOF) technology enables simultaneous quantification of more than 30 protein markers at single-cell resolution in a high-throughput fashion. Moreover, with distinct DNA and viability markers, single live cells can be explicitly selected in CyTOF. Here, leveraging the CyTOF data generated by the Human Pancreas Analysis Program, we characterized more than 12 million islet cells from 71 donors. Our data revealed continued age-related changes in islet endocrine cell compositions, but the maturity of endocrine cells is reached by 3 years of age. We also observed significant changes in beta cell numbers and key protein expressions, along with a significant increase in bihormonal cells in T1D donors. In contrast, T2D donors exhibited minimal islet remodeling events. Our data shine a light on the islet dynamics during development and diabetes pathogenesis and suggest divergent pathogenesis processes of T1D and T2D. Our comprehensive approach not only elucidates islet plasticity but also establishes a foundation for integrated CyTOF analysis in islet biology and beyond.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765787","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

Correction to: "Fibroblast Growth Factor 23 Neutralizing Antibody Ameliorates Abnormal Renal Phosphate Handling in Sickle Cell Disease Mice". 更正："成纤维细胞生长因子 23 中和抗体可改善镰状细胞病小鼠异常的肾脏磷酸盐处理能力"。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae106

引用次数: 0

Liraglutide Impacts Iron Homeostasis in a Murine Model of Hereditary Hemochromatosis. 利拉鲁肽影响遗传性血色素沉着病鼠模型中的铁稳态。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae090

Nadejda Bozadjieva-Kramer, Jae Hoon Shin, Neil B Blok, Chesta Jain, Nupur K Das, Joseph Polex-Wolf, Lotte Bjerre Knudsen, Yatrik M Shah, Randy J Seeley

{"title":"Liraglutide Impacts Iron Homeostasis in a Murine Model of Hereditary Hemochromatosis.","authors":"Nadejda Bozadjieva-Kramer, Jae Hoon Shin, Neil B Blok, Chesta Jain, Nupur K Das, Joseph Polex-Wolf, Lotte Bjerre Knudsen, Yatrik M Shah, Randy J Seeley","doi":"10.1210/endocr/bqae090","DOIUrl":"10.1210/endocr/bqae090","url":null,"abstract":"Classic hereditary hemochromatosis (HH) is an autosomal recessive iron-overload disorder resulting from loss-of-function mutations of the HFE gene. Patients with HH exhibit excessive hepatic iron accumulation that predisposes these patients to liver disease, including the risk for developing liver cancer. Chronic iron overload also poses a risk for the development of metabolic disorders such as obesity, type 2 diabetes, and insulin resistance. We hypothesized that liraglutide, GLP1 receptor agonist, alters iron metabolism while also reducing body weight and glucose tolerance in a mouse model of HH (global HFE knockout, HFE KO) and diet-induced obesity and glucose intolerance. The total body HFE KO and wild-type control mice were fed high-fat diet for 8 weeks. Mice were subdivided into liraglutide and vehicle-treated groups and received daily subcutaneous administration of the respective treatment once daily for 18 weeks. Liraglutide improved glucose tolerance and hepatic lipid markers and reduced body weight in a mouse model of HH, the HFE KO mouse, similar to wild-type controls. Importantly, our data show that liraglutide alters iron metabolism in HFE KO mice, leading to decreased circulating and stored iron levels in HFE KO mice. These observations highlight the potential that GLP1 receptor agonist could be used to reduce iron overload in addition to reducing body weight and improving glucose regulation in HH patients.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11311705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751377","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

Sex Differences in Alcohol Use: Is It All About Hormones? 饮酒的性别差异：都是荷尔蒙惹的祸？

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae088

Xavier J Maddern, Lauren T Ursich, Grace Bailey, Amy Pearl, Roberta G Anversa, Andrew J Lawrence, Leigh C Walker

引用次数: 0

Nongenomic ERα-AMPK Signaling Regulates Sex-Dependent Bcrp Transport Activity at the Blood-Brain Barrier. 非基因组ERα-AMPK信号调节血脑屏障上性别依赖性Bcrp转运活性

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-01 DOI: 10.1210/endocr/bqae081

David B Banks, Sydney L Lierz, Ronald E Cannon, Kenneth S Korach

{"title":"Nongenomic ERα-AMPK Signaling Regulates Sex-Dependent Bcrp Transport Activity at the Blood-Brain Barrier.","authors":"David B Banks, Sydney L Lierz, Ronald E Cannon, Kenneth S Korach","doi":"10.1210/endocr/bqae081","DOIUrl":"10.1210/endocr/bqae081","url":null,"abstract":"The blood-brain barrier (BBB) is an extensive capillary network that protects the brain from environmental and metabolic toxins while limiting drug delivery to the central nervous system (CNS). The ATP-binding cassette transporter breast cancer resistance protein (Bcrp) reduces drug delivery across the BBB by actively transporting its clinical substrates back into peripheral circulation before their entry into the CNS compartment. 17β-Estradiol (E2)-elicited changes in Bcrp transport activity and expression have been documented previously. We report a novel signaling mechanism by which E2 decreases Bcrp transport activity in mouse brain capillaries via rapid nongenomic signaling through estrogen receptor α. We extended this finding to investigate the effects of different endocrine-disrupting compounds (EDCs) and selective estrogen receptor modulators (SERMs) on Bcrp transport function. We also demonstrate sex-dependent expression of Bcrp and E2-sensitive Bcrp transport activity at the BBB ex vivo. This work establishes an explanted tissue-based model by which to interrogate EDCs and SERMs as modulators of nongenomic estrogenic signaling with implications for sex and hormonal regulation of therapeutic delivery into the CNS.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563023","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

Protein Tyrosine Phosphatase Receptors N and N2 Control Pituitary Melanotroph Development and POMC Expression. 蛋白酪氨酸磷酸酶受体 N 和 N2 控制垂体黑质发育和 POMC 的表达。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-01 DOI: 10.1210/endocr/bqae076

Stephanie Constantin, Srdjan J Sokanovic, Yuta Mochimaru, Aloa Lamarca Dams, Kosara Smiljanic, Rafael M Prévide, Naseratun Nessa, Gilberto N Carmona, Stanko S Stojilkovic

{"title":"Protein Tyrosine Phosphatase Receptors N and N2 Control Pituitary Melanotroph Development and POMC Expression.","authors":"Stephanie Constantin, Srdjan J Sokanovic, Yuta Mochimaru, Aloa Lamarca Dams, Kosara Smiljanic, Rafael M Prévide, Naseratun Nessa, Gilberto N Carmona, Stanko S Stojilkovic","doi":"10.1210/endocr/bqae076","DOIUrl":"10.1210/endocr/bqae076","url":null,"abstract":"The neuroendocrine marker genes Ptprn and Ptprn2 encode protein tyrosine phosphatase receptors N and N2, 2 members of protein tyrosine phosphatase receptors void of enzymatic activity, and whose function and mechanism of action have not been elucidated. To explore the role(s) of Ptprn and Ptprn2 on the hypothalamic-pituitary-adrenal axis, we used mice in which both genes were knocked out (DKO). The focus in this study was on corticotrophs and melanotrophs from the anterior and intermediate lobes of the pituitary gland, respectively. In both sexes, DKO caused an increase in the expression of the corticotroph/melanotroph genes Pomc and Tbx19 and the melanotroph-specific gene Pax7. We also found in vivo and in vitro increased synthesis and release of beta-endorphin, alpha-melanocyte-stimulating hormone, and ACTH in DKO mice, which was associated with increased serum corticosterone levels and adrenal mass. DKO also increased the expression of other melanotroph-specific genes, but not corticotroph-specific genes. The dopaminergic pathway in the hypothalamus and dopaminergic receptors in melanotrophs were not affected in DKO mice. However, hyperplasia of the intermediate lobe was observed in DKO females and males, accompanied by increased proopiomelanocortin immunoreactivity per cell. These results indicate that protein tyrosine phosphatase receptor type N contributes to hypothalamic-pituitary-adrenal function by being involved in processes governing postnatal melanotroph development and Pomc expression.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11242453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456022","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

Mice Lacking Mrs2 Magnesium Transporter are Hypophagic and Thin When Maintained on a High-Fat Diet. 缺乏 Mrs2 镁转运体的小鼠在以高脂肪饮食维持生命时，食欲减退，身体消瘦。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-01 DOI: 10.1210/endocr/bqae072

David R Powell, Deon D Doree, Melanie K Shadoan, Kenneth A Platt, Robert Brommage, Peter Vogel, Jean-Pierre Revelli

{"title":"Mice Lacking Mrs2 Magnesium Transporter are Hypophagic and Thin When Maintained on a High-Fat Diet.","authors":"David R Powell, Deon D Doree, Melanie K Shadoan, Kenneth A Platt, Robert Brommage, Peter Vogel, Jean-Pierre Revelli","doi":"10.1210/endocr/bqae072","DOIUrl":"10.1210/endocr/bqae072","url":null,"abstract":"Genes regulating body fat are shared with high fidelity by mice and humans, indicating that mouse knockout (KO) phenotyping might identify valuable antiobesity drug targets. Male Mrs2 magnesium transporter (Mrs2) KO mice were recently reported as thin when fed a high-fat diet (HFD). They also exhibited increased energy expenditure (EE)/body weight and had beiged adipocytes that, along with isolated hepatocytes, demonstrated increased oxygen consumption, suggesting that increased EE drove the thin phenotype. Here we provide our data on these and additional assays in Mrs2 KO mice. We generated Mrs2 KO mice by homologous recombination. HFD-fed male and female Mrs2 KO mice had significantly less body fat, measured by quantitative magnetic resonance, than wild-type (WT) littermates. HFD-fed Mrs2 KO mice did not demonstrate increased EE by indirect calorimetry and could not maintain body temperature at 4 °C, consistent with their decreased brown adipose tissue stores but despite increased beige white adipose tissue. Instead, when provided a choice between HFD and low-fat diet (LFD), Mrs2 KO mice showed a significant 15% decrease in total energy intake resulting from significantly lower HFD intake that offset numerically increased LFD intake. Food restriction studies performed using WT mice suggested that this decrease in energy intake could explain the loss of body fat. Oral glucose tolerance test studies revealed significantly improved insulin sensitivity in Mrs2 KO mice. We conclude that HFD-fed Mrs2 KO mice are thin with improved insulin sensitivity, and that this favorable metabolic phenotype is driven by hypophagia. Further evaluation is warranted to determine the suitability of MRS2 as a drug target for antiobesity therapeutics.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327399","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