Endocrinology最新文献_第8页

Hormonal Actions in the Medial Preoptic Area Governing Parental Behavior: Novel Insights From New Tools. 支配父母行为的内侧视前区荷尔蒙作用：新工具带来的新启示

IF 3.8 3区医学

Endocrinology Pub Date : 2024-11-26 DOI: 10.1210/endocr/bqae152

Tapasya Pal, Henry J McQuillan, Logan Wragg, Rosemary S E Brown

{"title":"Hormonal Actions in the Medial Preoptic Area Governing Parental Behavior: Novel Insights From New Tools.","authors":"Tapasya Pal, Henry J McQuillan, Logan Wragg, Rosemary S E Brown","doi":"10.1210/endocr/bqae152","DOIUrl":"10.1210/endocr/bqae152","url":null,"abstract":"The importance of hormones in mediating a behavioral transition in mammals from a virgin or nonparenting state to parental state was established around 50 years ago. Extensive research has since revealed a highly conserved neural circuit that underlies parental behavior both between sexes and between mammalian species. Within this circuit, hormonal action in the medial preoptic area of the hypothalamus (MPOA) has been shown to be key in timing the onset of parental behavior with the birth of offspring. However, the mechanism underlying how hormones act in the MPOA to facilitate this change in behavior has been unclear. Technical advances in neuroscience, including single cell sequencing, novel transgenic approaches, calcium imaging, and optogenetics, have recently been harnessed to reveal new insights into maternal behavior. This review aims to highlight how the use of these tools has shaped our understanding about which aspects of maternal behavior are regulated by specific hormone activity within the MPOA, how hormone-sensitive MPOA neurons integrate within the wider neural circuit that governs maternal behavior, and how maternal hormones drive changes in MPOA neuronal function during different reproductive states. Finally, we review our current understanding of hormonal modulation of MPOA-mediated paternal behavior in males.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575813","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

Selective Colocalization of GHSR and GLP-1R in a Subset of Hypothalamic Neurons and Their Functional Interaction. GHSR和GLP-1R在下丘脑神经元子集中的选择性共定位及其功能相互作用。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-11-26 DOI: 10.1210/endocr/bqae160

Julieta Aguggia, Gimena Fernandez, Daniela Cassano, Emilio R Mustafá, Silvia S Rodríguez, Sonia Cantel, Jean-Alain Fehrentz, Jesica Raingo, Helgi B Schiöth, Abdella M Habib, Pablo N De Francesco, Mario Perello

{"title":"Selective Colocalization of GHSR and GLP-1R in a Subset of Hypothalamic Neurons and Their Functional Interaction.","authors":"Julieta Aguggia, Gimena Fernandez, Daniela Cassano, Emilio R Mustafá, Silvia S Rodríguez, Sonia Cantel, Jean-Alain Fehrentz, Jesica Raingo, Helgi B Schiöth, Abdella M Habib, Pablo N De Francesco, Mario Perello","doi":"10.1210/endocr/bqae160","DOIUrl":"https://doi.org/10.1210/endocr/bqae160","url":null,"abstract":"The GH secretagogue receptor (GHSR) and the glucagon-like peptide-1 receptor (GLP-1R) are G protein-coupled receptors with critical, yet opposite, roles in regulating energy balance. Interestingly, these receptors are expressed in overlapping brain regions. However, the extent to which they target the same neurons and engage in molecular crosstalk remains unclear. To explore the potential colocalization of GHSR and GLP-1R in specific neurons, we performed detailed mapping of cells positive for both receptors using GHSR-eGFP reporter mice or wild-type mice infused with fluorescent ghrelin, alongside an anti-GLP-1R antibody. We found that GHSR+ and GLP-1R+ cells are largely segregated in the mouse brain. The highest overlap was observed in the hypothalamic arcuate nucleus, where 15% to 20% of GHSR+ cells were also GLP-1R+ cells. Additionally, we examined RNA-sequencing datasets from mouse and human brains to assess the fraction and distribution of neurons expressing both receptors, finding that double-positive Ghsr+/Glp1r+ cells are highly segregated, with a small subset of double-positive Ghsr+/Glp1r+ cells representing <10% of all Ghsr+ or Glp1r+ cells, primarily enriched in the hypothalamus. Furthermore, we conducted functional studies using patch-clamp recordings in a heterologous expression system to assess potential crosstalk in regulating presynaptic calcium channels. We provide the first evidence that liraglutide-evoked GLP-1R activity inhibits presynaptic channels, and that the presence of one GPCR attenuates the inhibitory effects of ligand-evoked activity mediated by the other on presynaptic calcium channels. In conclusion, while GHSR and GLP-1R can engage in molecular crosstalk, they are largely segregated across most neuronal types within the brain.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":"166 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906501","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: "Consensus PP1 Binding Motifs Regulate Transcriptional Corepression and Alternative RNA Splicing Activities of the Steroid Receptor Coregulators, p54nrb and PSF". 更正：“共识PP1结合基序调节类固醇受体共调节因子p54nrb和PSF的转录共抑制和选择性RNA剪接活性”。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-11-26 DOI: 10.1210/endocr/bqae163

引用次数: 0

Chrna2-driven CRE Is Expressed in Beige Adipocytes. Chrna2 驱动的 CRE 在米色脂肪细胞中表达。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-11-26 DOI: 10.1210/endocr/bqae153

Kezhou Zhu, Shanshan Liu, Yunying Huang, Biyang Zhang, Nadia Houssein, Jun Wu

{"title":"Chrna2-driven CRE Is Expressed in Beige Adipocytes.","authors":"Kezhou Zhu, Shanshan Liu, Yunying Huang, Biyang Zhang, Nadia Houssein, Jun Wu","doi":"10.1210/endocr/bqae153","DOIUrl":"10.1210/endocr/bqae153","url":null,"abstract":"Significant research interest has been focused on beige adipocytes, the activation of which improves glucose and lipid homeostasis, therefore representing new therapeutic opportunities for metabolic diseases. Various Cre/Lox-based strategies have been used to investigate the developmental history of beige adipocytes and how these cells adapt to environmental changes. Despite the significant advancement of our understanding of beige adipocyte biology, much of the molecular insights of the beige adipocyte, including its origin and cell type-specific function, remain to be further illustrated. It has previously been shown that Chrna2 (cholinergic receptor nicotinic alpha 2 subunit) has selective functionality in beige adipocytes. In this study, we explore the Chrna2-Cre-driven reporter expression in mouse beige adipocytes in vivo and in vitro. Our findings indicate that Chrna2-Cre expression is present selectively in multiple locular beige adipocytes in subcutaneous inguinal white adipose tissue (iWAT) and differentiated stromal vascular fraction from iWAT. Chrna2-Cre expression was detected in iWAT of young pups and mice after cold exposure where a significant number of beige adipocytes are present. Chrna2-Cre-driven reporter expression is permanent in iWAT postlabeling and can be detected in the iWAT of adult mice or mice that have been housed extensively at thermoneutrality after cold exposure, even though only \"inactive dormant\" beige adipocytes are present in these mice. Chrna2-Cre expression can also be increased by rosiglitazone treatment and β-adrenergic activation. This research, therefore, introduces the Chrna2-Cre line as a valuable tool for tracking the development of beige adipocytes and investigating beige fat function.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616263","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

Postnatal Ovarian Transdifferentiation in the Absence of Estrogen Receptor Signaling Is Dependent on Genetic Background. 缺失雌激素受体信号的产后卵巢转分化取决于遗传背景

IF 3.8 3区医学

Endocrinology Pub Date : 2024-11-26 DOI: 10.1210/endocr/bqae157

April K Binder, Katherine A Burns, Karina F Rodriguez, Katherine Hamilton, Fernando Pardo-Manuel de Villena, Kenneth S Korach

{"title":"Postnatal Ovarian Transdifferentiation in the Absence of Estrogen Receptor Signaling Is Dependent on Genetic Background.","authors":"April K Binder, Katherine A Burns, Karina F Rodriguez, Katherine Hamilton, Fernando Pardo-Manuel de Villena, Kenneth S Korach","doi":"10.1210/endocr/bqae157","DOIUrl":"10.1210/endocr/bqae157","url":null,"abstract":"Normal ovarian function requires the expression of estrogen receptors α (ESR1) and β (ESR2) in distinct cell types within the ovary. The double estrogen receptor knockout (αβERKO) ovary had the appearance of seminiferous tubule-like structures that expressed SOX9; this phenotype was lost when the animals were repeatedly backcrossed to the C57BL/6J genetic background. A new line of ERKO mice, Ex3αβERKO, was developed for targeted disruption on a mixed genetic background. Histological examination of the ovaries in the Ex3αβERKO showed the appearance of seminiferous tubule-like structures in mice aged 6 to 12 months. These dismorphogenic regions have cells that no longer express granulosa cell-specific FOXL2, while other cells express Sertoli cell-specific SOX9 as examined by immunohistochemistry. Whole ovarian gene expression analysis in Ex3αERKO, Ex3βRKO, and Ex3αβERKO found many genes differentially expressed compared to controls with one Esr1 and Esr2 allele. The genes specific to the Ex3αβERKO ovary were compared to other models of postnatal ovarian transdifferentiation, identifying 21 candidate genes. To examine the genetic background contributions, DNA was isolated from αβERKO mice that did not show ovarian transdifferentiation and compared to DNA from Ex3αβERKO using Mouse Diversity Array. A genomic region putatively associated with transdifferentiation was identified on Chr18 (5-15 M) and genes in this region were compared to the genes differentially expressed in models of ovarian transdifferentiation. This work demonstrates the importance of ESRs in maintaining granulosa cell differentiation within the ovary, identifies several potential gene candidates, and suggests that genetic background can be a confounding factor.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686317","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

Solving the Mystery of the Neonatal GH Surge. 解决新生儿生长激素激增之谜。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-11-26 DOI: 10.1210/endocr/bqae158

Angela K Odle, Gwen V Childs

引用次数: 0

Physiology and Pharmacology of Effects of GLP-1-based Therapies on Gastric, Biliary and Intestinal Motility. 基于 GLP-1 的疗法对胃、胆道和肠道运动影响的生理学和药理学。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-11-26 DOI: 10.1210/endocr/bqae155

Ryan J Jalleh, Chinmay S Marathe, Christopher K Rayner, Karen L Jones, Mahesh M Umapathysivam, Tongzhi Wu, Daniel R Quast, Mark P Plummer, Michael A Nauck, Michael Horowitz

{"title":"Physiology and Pharmacology of Effects of GLP-1-based Therapies on Gastric, Biliary and Intestinal Motility.","authors":"Ryan J Jalleh, Chinmay S Marathe, Christopher K Rayner, Karen L Jones, Mahesh M Umapathysivam, Tongzhi Wu, Daniel R Quast, Mark P Plummer, Michael A Nauck, Michael Horowitz","doi":"10.1210/endocr/bqae155","DOIUrl":"10.1210/endocr/bqae155","url":null,"abstract":"Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual GLP-1- and glucose-dependent insulinotropic polypeptide receptor co-agonist tirzepatide (referred to here collectively as \"GLP-1-based therapy\") are incretin-based therapies being used increasingly in the management of both type 2 diabetes and obesity. They are now recognized to have beneficial effects beyond improved glycemic control and weight loss, including cardiovascular and renal protection. GLP-1-based therapy also slows gastric emptying, which has benefits (lowering postprandial glucose), but also potential risks (eg, hypoglycemia in individuals on insulin or sulphonylurea therapy). Their effects on the gallbladder may also be beneficial, contributing to reducing postprandial triglycerides, but they also potentially increase the risk of biliary disease. In this review, we summarize the effects of GLP-1 and incretin-based therapeutics on gastric, biliary and small intestinal function. An improved understanding of these effects will optimize the use of these drugs.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680882","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

Femoral Artery Infusion of αMSH Increases Muscle Thermogenesis and Promotes Glucose Uptake in Ovariectomized Ewes. 股动脉输注αMSH可增加卵巢切除母羊的肌肉产热并促进葡萄糖摄取。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-11-26 DOI: 10.1210/endocr/bqae156

Belinda A Henry, Michael A Cowley, Zane B Andrews, Iain J Clarke

{"title":"Femoral Artery Infusion of αMSH Increases Muscle Thermogenesis and Promotes Glucose Uptake in Ovariectomized Ewes.","authors":"Belinda A Henry, Michael A Cowley, Zane B Andrews, Iain J Clarke","doi":"10.1210/endocr/bqae156","DOIUrl":"10.1210/endocr/bqae156","url":null,"abstract":"The melanocortin system is fundamental to neural control of energy balance and long-term weight regulation. Recent evidence shows that melanocortins also act at peripheral tissues to regulate metabolism, independent of the brain or the sympathetic nervous system (SNS). One such target is skeletal muscle, which contributes to energy expenditure through changes in adaptive thermogenesis. We aimed to determine 1) whether direct femoral infusion of α-melanocyte-stimulating hormone (αMSH) could increase muscle heat production independent of SNS activation and 2) if αMSH-induced skeletal muscle heat production was associated with altered mitochondrial function. Dataloggers were implanted into one hind leg of ovariectomized ewes and set to record vastus lateralis temperature every 15 minutes. A cannula was inserted into one femoral artery for infusion of either αMSH (0.1 µg/h) or saline. Femoral infusion of αMSH increased (P < .0001) skeletal muscle heat production, without effect on food intake. State 4 respiration increased (P < .05) and the respiratory control ratio decreased (P < .05) in mitochondria isolated from αMSH-treated animals. In addition, femoral infusion of αMSH reduced plasma glucose concentration in the femoral, but not the jugular vein; there was no effect of αMSH treatment on nonesterified fatty acid concentrations. These data suggest that αMSH can act locally to increase glucose uptake. We further show that blockade of the α- and β-adrenergic limbs of the SNS with either phentolamine or propranolol infusion had no effect on αMSH-induced skeletal muscle heat production. Overall, we show that αMSH acts directly at skeletal muscle to promote glucose uptake and increase energy expenditure via mitochondrial thermogenesis.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667482","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

Structural Insights Into Thyroid Hormone Receptors. 甲状腺激素受体的结构研究。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-11-26 DOI: 10.1210/endocr/bqae154

Izabella Tambones, Albane le Maire

{"title":"Structural Insights Into Thyroid Hormone Receptors.","authors":"Izabella Tambones, Albane le Maire","doi":"10.1210/endocr/bqae154","DOIUrl":"10.1210/endocr/bqae154","url":null,"abstract":"Thyroid hormone receptors (TRs) are essential components of the endocrine system, mediating the cellular effects of thyroid hormones. The 2 TR genes, THRA and THRB, encode 4 isoforms, with TRα1 and TRβ1 being the most prevalent. TRs are ligand-dependent transcription factors and members of the nuclear receptor superfamily, indispensable for human growth, development, and metabolism. Dysfunctional TR signaling can lead to conditions such as resistance to thyroid hormone (RTH) syndrome, thyroid cancer, and metabolic disorders. Structurally, TRs comprise several domains: a variable N-terminal domain, a conserved DNA-binding domain, and a ligand-binding domain that mediates interaction with hormones and transcriptional coregulators. TRs predominantly function as heterodimers with the retinoid X receptor (RXR), binding to thyroid hormone response elements in target genes to regulate their transcription. This review examines the structural studies on TRs, primarily performed through x-ray crystallography, that have provided detailed insights into TR functions, including DNA recognition, ligand binding, and coregulator interactions. We also discuss how these findings have deepened our understanding of TR mechanisms and contributed to the interpretation of pathogenic mutations.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616284","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

Development and Characterization of 3-Dimensional Cell Culture Models of Adrenocortical Carcinoma. 肾上腺皮质癌三维（3D）细胞培养模型的开发与表征。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-11-26 DOI: 10.1210/endocr/bqae159

Sarah Feely, Nathan Mullen, Padraig T Donlon, Eileen Reidy, Ritihaas Surya Challapalli, Mariam Hassany, Anna Sorushanova, Eduardo Ribes Martinez, Peter Owens, Anne Marie Quinn, Abhay Pandit, Brendan Harhen, David P Finn, Constanze Hantel, Martin O'Halloran, Punit Prakash, Michael C Dennedy

{"title":"Development and Characterization of 3-Dimensional Cell Culture Models of Adrenocortical Carcinoma.","authors":"Sarah Feely, Nathan Mullen, Padraig T Donlon, Eileen Reidy, Ritihaas Surya Challapalli, Mariam Hassany, Anna Sorushanova, Eduardo Ribes Martinez, Peter Owens, Anne Marie Quinn, Abhay Pandit, Brendan Harhen, David P Finn, Constanze Hantel, Martin O'Halloran, Punit Prakash, Michael C Dennedy","doi":"10.1210/endocr/bqae159","DOIUrl":"10.1210/endocr/bqae159","url":null,"abstract":"Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex that is associated with a poor prognosis. Developing effective treatment options for ACC is challenging owing to the current lack of representative preclinical models. This study addressed this limitation by developing and characterizing 3-dimensional (3D) cell cultures incorporating the ACC cell lines, MUC-1, HAC15, and H295R in a type I collagen matrix. ACC tissue samples were analyzed by immunohistochemistry to determine the presence of type I collagen in the tumor microenvironment. Cell viability and proliferation were assessed using flow cytometry and confocal microscopy. mRNA expression of steroidogenic enzymes and steroid secretion was analyzed by comparing the 3D and monolayer cell culture models. All cells were successfully cultured in a type I collagen matrix, which is highly expressed in the ACC tumor microenvironment and showed optimal viability until day 7. All 3 models showed increased metabolic and proliferative activity over time. Three-dimensional cell cultures were steroidogenic and demonstrated increased resistance to the gold standard chemotherapy, mitotane, compared with monolayer. The use of these models may lead to an improved understanding of disease pathology and provide a better representative platform for testing and screening of potential therapies.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827740","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