Journal of molecular endocrinology最新文献_第7页

m6A readers, writers, erasers, and the m6A epitranscriptome in breast cancer. 乳腺癌中的 m6A 阅读器、写作器、擦除器和 m6A 表转录组。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-12-21 Print Date: 2023-02-01 DOI: 10.1530/JME-22-0110

Belinda J Petri, Carolyn M Klinge

引用次数: 0

Adipocyte signaling affects thyroid-specific gene expression via down-regulation of TTF-2/FOXE1. 脂肪细胞信号通过下调TTF-2/FOXE1影响甲状腺特异性基因的表达。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-12-12 Print Date: 2023-01-01 DOI: 10.1530/JME-22-0129

Michela Zamboni, Georgios Strimpakos, Eleonora Poggiogalle, Lorenzo Maria Donini, Donato Civitareale

引用次数: 0

Structure of full-length TSH receptor in complex with antibody K1-70™. 全长TSH受体与抗体K1-70复合物的结构。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-12-07 Print Date: 2023-01-01 DOI: 10.1530/JME-22-0120

Ricardo Núñez Miguel, Paul Sanders, Lloyd Allen, Michele Evans, Matthew Holly, William Johnson, Andrew Sullivan, Jane Sanders, Jadwiga Furmaniak, Bernard Rees Smith

{"title":"Structure of full-length TSH receptor in complex with antibody K1-70™.","authors":"Ricardo Núñez Miguel, Paul Sanders, Lloyd Allen, Michele Evans, Matthew Holly, William Johnson, Andrew Sullivan, Jane Sanders, Jadwiga Furmaniak, Bernard Rees Smith","doi":"10.1530/JME-22-0120","DOIUrl":"10.1530/JME-22-0120","url":null,"abstract":"Determination of the full-length thyroid-stimulating hormone receptor (TSHR) structure by cryo-electron microscopy (cryo-EM) is described. The TSHR complexed with human monoclonal TSHR autoantibody K1-70™ (a powerful inhibitor of TSH action) was detergent solubilised, purified to homogeneity and analysed by cryo-EM. The structure (global resolution 3.3 Å) is a monomer with all three domains visible: leucine-rich domain (LRD), hinge region (HR) and transmembrane domain (TMD). The TSHR extracellular domain (ECD, composed of the LRD and HR) is positioned on top of the TMD extracellular surface. Extensive interactions between the TMD and ECD are observed in the structure, and their analysis provides an explanation of the effects of various TSHR mutations on TSHR constitutive activity and on ligand-induced activation. K1-70™ is seen to be well clear of the lipid bilayer. However, superimposition of M22™ (a human monoclonal TSHR autoantibody which is a powerful stimulator of the TSHR) on the cryo-EM structure shows that it would clash with the bilayer unless the TSHR HR rotates upwards as part of the M22™ binding process. This rotation could have an important role in TSHR stimulation by M22™ and as such provides an explanation as to why K1-70™ blocks the binding of TSH and M22™ without activating the receptor itself.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"70 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9087634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1

The epidermal growth factor receptor in healthy pregnancy and preeclampsia. 健康妊娠和子痫前期的表皮生长因子受体。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-12-07 Print Date: 2023-01-01 DOI: 10.1530/JME-22-0105

Luca Clemente, Ian M Bird

{"title":"The epidermal growth factor receptor in healthy pregnancy and preeclampsia.","authors":"Luca Clemente, Ian M Bird","doi":"10.1530/JME-22-0105","DOIUrl":"10.1530/JME-22-0105","url":null,"abstract":"The epidermal growth factor receptor (EGFR) is expressed robustly in the placenta, and critical processes of pregnancy such as placental growth and trophoblast fusion are dependent on EGFR function. However, the role that aberrant EGFR signaling might play in the etiology and/or maintenance of preeclampsia (PE) remains largely unexplored. Recently, we have shown that overexpression of EGFR in cultured uterine artery endothelial cells (UAEC), which express little endogenous EGFR, remaps responsiveness away from vascular endothelial growth factor receptor (VEGFR) signaling and toward EGFR, suggesting that endothelial EGFR expression may be kept low to preserve VEGFR control of angiogenesis. Here we will consider the evidence for the possibility that the endothelial dysfunction observed in PE might in some cases result from elevation of endothelial EGFR. During pregnancy, trophoblasts are known to synthesize large amounts of EGFR protein, and the placenta regularly releases syncytiotrophoblast-derived exosomes and microparticles into the maternal circulation. Although there are no reports of elevated EGFR gene expression in preeclamptic endothelial cells, the ongoing shedding of placental vesicles into the vascular system raises the possibility that EGFR-rich vesicles might fuse with endothelium, thereby contributing to the symptoms of PE by interrupting angiogenesis and blocking pregnancy-adapted vasodilatory function.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"70 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9742168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9840994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 1

Embarking on an adventure of early career academic leadership. 开始职业生涯初期的学术领导探险。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2022-12-07 Print Date: 2023-01-01 DOI: 10.1530/JME-22-0049

Tijana Mitić

{"title":"Embarking on an adventure of early career academic leadership.","authors":"Tijana Mitić","doi":"10.1530/JME-22-0049","DOIUrl":"10.1530/JME-22-0049","url":null,"abstract":"Leading a research group as an early career researcher (ECR) in academia presents many challenges. First, it imposes many additional pressures on individuals, causing fear of missing out on a great opportunity that could advance your career. Together, the unsettling nature of short-term or temporary contracts, lack of guidance and the imposter syndrome can trigger a crisis in future leadership. Most leadership positions at universities are held by senior colleagues. ECRs have modest input in decision-making, due to a requirement for specific leadership training and experience with oversight that precedes suitable decision-making. The turbulence of the unprecedented world COVID-19 crisis has been felt disproportionally by many researchers, intensely by those with caring responsibilities. In the current academic climate, navigating either between your postdoctoral or fellowship project, leading others, taking strategic project directions, mentoring or networking may feel like too much. This editorial expresses views on the current state of the matter in academia with suggestions for helpful strategies to employ to meet research endpoints. It also addresses some challenges that new principal investigators and academic leaders may face due to external or institutional change, and provides some tangible advice with action points.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"70 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10853248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Retinoid metabolism: new insights. 视黄醇代谢：新见解。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-10-11 Print Date: 2022-11-01 DOI: 10.1530/JME-22-0082

Lorraine J Gudas

{"title":"Retinoid metabolism: new insights.","authors":"Lorraine J Gudas","doi":"10.1530/JME-22-0082","DOIUrl":"10.1530/JME-22-0082","url":null,"abstract":"Vitamin A (retinol) is a critical micronutrient required for the control of stem cell functions, cell differentiation, and cell metabolism in many different cell types, both during embryogenesis and in the adult organism. However, we must obtain vitamin A from food sources. Thus, the uptake and metabolism of vitamin A by intestinal epithelial cells, the storage of vitamin A in the liver, and the metabolism of vitamin A in target cells to more biologically active metabolites, such as retinoic acid (RA) and 4-oxo-RA, must be precisely regulated. Here, I will discuss the enzymes that metabolize vitamin A to RA and the cytochrome P450 Cyp26 family of enzymes that further oxidize RA. Because much progress has been made in understanding the regulation of ALDH1a2 (RALDH2) actions in the intestine, one focus of this review is on the metabolism of vitamin A in intestinal epithelial cells and dendritic cells. Another focus is on recent data that 4-oxo-RA is a ligand required for the maintenance of hematopoietic stem cell dormancy and the important role of RARβ (RARB) in these stem cells. Despite this progress, many questions remain in this research area, which links vitamin A metabolism to nutrition, immune functions, developmental biology, and nuclear receptor pharmacology.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"69 4","pages":"T37-T49"},"PeriodicalIF":3.5,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9286094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 9

Retinoic acid receptor structures: the journey from single domains to full-length complex. 视黄酸受体结构:从单一结构域到全长复合体的历程。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2022-10-11 Print Date: 2022-11-01 DOI: 10.1530/JME-22-0113

Fraydoon Rastinejad

{"title":"Retinoic acid receptor structures: the journey from single domains to full-length complex.","authors":"Fraydoon Rastinejad","doi":"10.1530/JME-22-0113","DOIUrl":"10.1530/JME-22-0113","url":null,"abstract":"The retinoic acid receptors (RARα, β, and γ) are multi-domain polypeptides that heterodimerize with retinoid X receptors (RXRα, β, and γ) to form functional transcription factors. Understanding the three-dimensional molecular organization of these nuclear receptors (NRs) began with RAR and RXR DNA-binding domains (DBDs), and were followed with studies on isolated ligand-binding domains (LBDs). The more complete picture emerged in 2017 with the multi-domain crystal structure of RXRα-RARβ on its response element with retinoic acid molecules and coactivator segments on both proteins. The analysis of that structure and its complementary studies have clarified the direct communication pathways within RXR-RAR polypeptides, through which DNA binding, protein-ligand, and protein-protein interactions are integrated for overall functional responses. Understanding the molecular connections in the RXR-RAR complex has benefited from direct observations of the multi-domain structures of RXRα-PPARγ, RXRα-LXRβ, HNF-4α homodimer, and androgen receptor homodimer, each bound to its response element. These comprehensive NR structures show unique quaternary architectures, yet all have DBD-DBD, LBD-LBD, and DBD-LBD domain-domain contacts within them. These convergence zones allow signals from discrete domains of their polypeptides to be propagated and integrated across their entire complex, shaping their overall responses in an allosteric fashion.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"69 4","pages":"T25-T36"},"PeriodicalIF":3.6,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9109310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Retinoic acid, RARs and early development. 维甲酸、RARs和早期发育。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-10-11 Print Date: 2022-11-01 DOI: 10.1530/JME-22-0041

Marie Berenguer, Gregg Duester

{"title":"Retinoic acid, RARs and early development.","authors":"Marie Berenguer, Gregg Duester","doi":"10.1530/JME-22-0041","DOIUrl":"10.1530/JME-22-0041","url":null,"abstract":"Vitamin A (retinol) is an important nutrient for embryonic development and adult health. Early studies identified retinoic acid (RA) as a metabolite of retinol, however, its importance was not apparent. Later, it was observed that RA treatment of vertebrate embryos had teratogenic effects on limb development. Subsequently, the discovery of nuclear RA receptors (RARs) revealed that RA controls gene expression directly at the transcriptional level through a process referred to as RA signaling. This important discovery led to further studies demonstrating that RA and RARs are required for normal embryonic development. The determination of RA function during normal development has been challenging as RA gain-of-function studies often lead to conclusions about normal development that conflict with RAR or RA loss-of-function studies. However, genetic loss-of-function studies have identified direct target genes of endogenous RA/RAR that are required for normal development of specific tissues. Thus, genetic loss-of-function studies that eliminate RARs or RA-generating enzymes have been instrumental in revealing that RA signaling is required for normal early development of many organs and tissues, including the hindbrain, posterior body axis, somites, spinal cord, forelimbs, heart, and eye.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"1 1","pages":"T59-T67"},"PeriodicalIF":3.5,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41363455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 10

Female reproductive dysfunctions and the gut microbiota. 女性生殖功能障碍和肠道菌群。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-08-04 Print Date: 2022-10-01 DOI: 10.1530/JME-21-0238

Sangappa B Chadchan, Vertika Singh, Ramakrishna Kommagani

{"title":"Female reproductive dysfunctions and the gut microbiota.","authors":"Sangappa B Chadchan, Vertika Singh, Ramakrishna Kommagani","doi":"10.1530/JME-21-0238","DOIUrl":"10.1530/JME-21-0238","url":null,"abstract":"The gut microbiome is considered an endocrine organ that can influence distant organs and associated biological pathways. Recent advances suggest that gut microbial homeostasis is essential for reproductive health and that perturbations in the gut microbiota can lead to reproductive pathologies. This review provides an updated overview of the relationship between the gut microbiome and female reproductive diseases. Specifically, we highlight the most recent findings on the gut microbiome in gynecological pathologies including polycystic ovarian syndrome, endometriosis, and endometrial cancer. Most studies revealed associations between altered gut microbial compositions and these reproductive diseases, though few have suggested cause-effect relationships. Future studies should focus on determining the molecular mechanisms underlying associations between gut microbiota and reproductive diseases. Understanding this bidirectional relationship could lead to the development of novel and effective strategies to prevent, diagnose, and treat female reproductive organ-related diseases.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"69 3","pages":"R81-R94"},"PeriodicalIF":3.5,"publicationDate":"2022-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031513/pdf/nihms-1825897.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9170927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 14

Insulin signaling in the heart is impaired by growth hormone: a direct and early event. 心脏中的胰岛素信号受到生长激素的损害:这是一个直接和早期的事件。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-08-01 DOI: 10.1530/JME-21-0242

Marina C Muñoz, Verónica G Piazza, Valeria Burghi, Jorge F Giani, Carolina S Martinez, Nadia S Cicconi, Nadia V Muia, Yimin Fang, Sergio Lavandero, Ana I Sotelo, Andrzej Bartke, Patricia A Pennisi, Fernando P Dominici, Johanna G Miquet

{"title":"Insulin signaling in the heart is impaired by growth hormone: a direct and early event.","authors":"Marina C Muñoz, Verónica G Piazza, Valeria Burghi, Jorge F Giani, Carolina S Martinez, Nadia S Cicconi, Nadia V Muia, Yimin Fang, Sergio Lavandero, Ana I Sotelo, Andrzej Bartke, Patricia A Pennisi, Fernando P Dominici, Johanna G Miquet","doi":"10.1530/JME-21-0242","DOIUrl":"https://doi.org/10.1530/JME-21-0242","url":null,"abstract":"Growth hormone (GH) exerts major actions in cardiac growth and metabolism. Considering the important role of insulin in the heart and the well-established anti-insulin effects of GH, cardiac insulin resistance may play a role in the cardiopathology observed in acromegalic patients. As conditions of prolonged exposure to GH are associated with a concomitant increase of circulating GH, IGF-1 and insulin levels, to dissect the direct effects of GH, in this study we evaluated the activation of insulin signaling in the heart using four different models: 1) transgenic mice overexpressing GH, with chronically elevated GH, IGF-1 and insulin circulating levels, 2) liver IGF-1-deficient mice, with chronically elevated GH and insulin but decreased IGF-1 circulating levels, 3) mice treated with GH for a short period of time, and 4) primary culture of rat cardiomyocytes incubated with GH. Despite the differences in the development of cardiomegaly and in the metabolic alterations among the three experimental mouse models analysed, exposure to GH was consistently associated with a decreased response to acute insulin stimulation in the heart at the receptor level and through the PI3K/Akt pathway. Moreover, a blunted response to insulin stimulation of this signaling pathway was also observed in cultured cardiomyocytes of neonatal rats incubated with GH. Therefore, the key novel finding of this work is that impairment of insulin signaling in the heart is a direct and early event observed as a consequence of exposure to GH, which may play a major role in the development of cardiac pathology.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"69 2","pages":"357-376"},"PeriodicalIF":3.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339477/pdf/nihms-1813926.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9968262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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