Journal of molecular endocrinology最新文献_第9页

Loss of HOXA10 causes endometrial hyperplasia progressing to endometrial cancer. HOXA10的缺失导致子宫内膜增生进展为子宫内膜癌。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-08-26 Print Date: 2022-10-01 DOI: 10.1530/JME-22-0051

Anuradha Mishra, Nirmalya Ganguli, Subeer S Majumdar, Deepak Modi

引用次数: 0

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

IF 3.6 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":3.6,"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: 0

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

Temporal regulation of interferon signalling in human EndoC-βH1 cells. 人EndoC-βH1细胞干扰素信号传导的时间调控。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2022-05-19 DOI: 10.1530/JME-21-0224

Shalinee Dhayal, Kaiyven Afi Leslie, Mohammad Baity, Pouria Akhbari, Sarah J Richardson, Mark A Russell, Noel G Morgan

{"title":"Temporal regulation of interferon signalling in human EndoC-βH1 cells.","authors":"Shalinee Dhayal, Kaiyven Afi Leslie, Mohammad Baity, Pouria Akhbari, Sarah J Richardson, Mark A Russell, Noel G Morgan","doi":"10.1530/JME-21-0224","DOIUrl":"10.1530/JME-21-0224","url":null,"abstract":"During the development of type 1 diabetes, interferons (IFN) are elaborated from islet-infiltrating immune cells and/or from virally infected β-cells. They act via specific receptors to increase, acutely, the phosphorylation of the transcription factors STAT1 and 2. However, the longer-term impacts of chronic IFN stimulation are poorly understood and were investigated in the current study. Human EndoC-βH1 cells were treated with IFNα, IFNγ or IFNλ either acutely (<2 h) or chronically (≥24 h) and STAT phosphorylation, expression and activity were assessed by Western blotting and transcriptional reporter assays. Exposure of β-cells to IFNα or IFNλ induced a swift increase in the phosphorylation of both STAT1 and STAT2, whereas IFNγ increased only pSTAT1. Over more extended periods (≥24 h), STAT phosphorylation declined but STAT1 and STAT2 expression were enhanced in a sustained manner. All IFNs stimulated ISRE transcriptional activity (but with different time courses), whereas GAS activity was responsive only to IFNγ. The re-addition of a second bolus of IFNα, 24 h after an initial dose, failed to cause renewed STAT1/2 phosphorylation. By contrast, when IFNγ was added 24 h after exposure to IFNα, rapid STAT1 phosphorylation was re-initiated. Exposure of β-cells to IFNs leads to rapid, transient, STAT phosphorylation and to slower and more sustained increases in total STAT1/2 levels. The initial phosphorylation response is accompanied by marked desensitisation to the cognate agonist. Together, the results reveal that the response of β-cells to IFNs is regulated both temporally and quantitatively to achieve effective signal integration.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"69 2","pages":"299-313"},"PeriodicalIF":3.6,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10099516","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

Estrogen-mediated differential protein regulation and signal transduction in rheumatoid arthritis. 类风湿关节炎中雌激素介导的差异蛋白调控和信号转导。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-05-09 DOI: 10.1530/JME-22-0010

Debolina Chakraborty, Ashish Sarkar, Sonia Mann, Prachi Agnihotri, Mohd Saquib, Swati Malik, Rajkamal Kumavat, Anushka Mathur, Sagarika Biswas

{"title":"Estrogen-mediated differential protein regulation and signal transduction in rheumatoid arthritis.","authors":"Debolina Chakraborty, Ashish Sarkar, Sonia Mann, Prachi Agnihotri, Mohd Saquib, Swati Malik, Rajkamal Kumavat, Anushka Mathur, Sagarika Biswas","doi":"10.1530/JME-22-0010","DOIUrl":"https://doi.org/10.1530/JME-22-0010","url":null,"abstract":"Exploration of the dual and opposing facets of estrogen necessitates a clear understanding to diminish the controversy of estrogen regulation in averting the systemic, autoimmune, joint degrading disorder, and rheumatoid arthritis (RA). Experimental evidences consider estrogen as a pivotal enzyme to modulate the disease progression via managing several cellular mechanisms targeting inflammatory markers such as TNF, ILs, nuclear factor kappa B, and other regulatory proteins like matrix metalloproteinases impeding joint erosion and cartilage degradation. Estrogen modulates cellular signaling associated with inflammation, oxidative stress, related cardiovascular risk, and miRNA regulation during RA progression. Studies determining estrogen regulation in RA complicate the resemblance of the outcome as they represent both hyper and hypo level of estrogen is linked to the disease. Although some reports deliver estrogen as malign, there is now increasing evidence of rendering protection dose dependently. Variation in estrogen level causes differential expression of certain proteins and their related signaling which is directly or indirectly linked to RA pathogenesis. This review summarizes the variations in protein expression levels by focusing on the in vitro, in vivo,and clinical studies of estrogen deficiency and treatment. Construction of protein-protein interaction network, GO, and KEGG pathway enrichment analysis of the differentially expressed proteins assist in hypothesizing a potential molecular mechanism of estrogen in RA via in silico studies. Targeting these differential proteins can emerge a new path for developing advanced therapeutic strategies.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":"R25-R43"},"PeriodicalIF":3.5,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40319536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 6

Personalised medicines for familial hypercalcemia and hyperparathyroidism. 个体化药物治疗家族性高钙血症和甲状旁腺功能亢进。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-05-09 DOI: 10.1530/JME-21-0263

Tracy Maree Josephs, Frankie Zhang, Le Vi Dinh, Andrew N Keller, Arthur D Conigrave, Ben Capuano, Karen Joan Gregory, Katie Leach

{"title":"Personalised medicines for familial hypercalcemia and hyperparathyroidism.","authors":"Tracy Maree Josephs, Frankie Zhang, Le Vi Dinh, Andrew N Keller, Arthur D Conigrave, Ben Capuano, Karen Joan Gregory, Katie Leach","doi":"10.1530/JME-21-0263","DOIUrl":"https://doi.org/10.1530/JME-21-0263","url":null,"abstract":"Loss-of-function calcium-sensing receptor (CASR) mutations cause mineral metabolism disorders, familial hypocalciuric hypercalcemia, or neonatal severe hyperparathyroidism and increase the risk of femoral fracture, chronic kidney disease, coronary heart disease, and other diseases. In severe cases, CaSR mutations are lethal. Off-label use of the CaSR-positive allosteric modulator (PAM), cinacalcet, corrects hypercalcemia in some patients with CaSR mutations. However, other patients remain unresponsive to cinacalcet, attesting to the need for novel treatments. Here, we compared the effects of cinacalcet to two other clinically approved synthetic CaSR activators, evocalcet and etelcalcetide, as well as a novel PAM, 1-(2,4-dimethylphenyl)-1-(4,5-dimethylthiazol-2-yl)ethan-1-ol (MIPS-VD-836-108) on clinically relevant CaSR mutations. We assessed the compounds in CaSR-expressing HEK293 cells for correction of mutation-induced impairments in intracellular calcium (Ca2+i) mobilization and cell surface expression. While cinacalcet, MIPS-VD-836-108 and evocalcet rescued the signaling of cell surface-expressed mutants, albeit to varying degrees, etelcalcetide was ineffective. Cinacalcet and evocalcet, but not MIPS-VD-836-108 or etelcalcetide, restored the expression of a R680H mutant. However, no compound rescued expression of I81K and C582R mutants or a receptor missing 77 amino acids in the extracellular domain mimicking deletion of CASRexon 5, which impairs CaSR function. These data suggest specific compounds may be clinically effective in some patients with CaSR mutations, but other patients will remain refractory to treatment with currently available CaSR-targeting activators, highlighting the need for new generation drugs to rescue both the signaling and expression of mutant CaSRs.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":"243-257"},"PeriodicalIF":3.5,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40315435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Genetic bases of pheochromocytoma and paraganglioma. 嗜铬细胞瘤和副神经节瘤的遗传基础。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-05-07 DOI: 10.1530/endoabs.81.s9.1

A. Cascón, Bruna Calsina, María Monteagudo, Sara Mellid, Alberto Díaz-Talavera, M. Currás-Freixes, M. Robledo

{"title":"Genetic bases of pheochromocytoma and paraganglioma.","authors":"A. Cascón, Bruna Calsina, María Monteagudo, Sara Mellid, Alberto Díaz-Talavera, M. Currás-Freixes, M. Robledo","doi":"10.1530/endoabs.81.s9.1","DOIUrl":"https://doi.org/10.1530/endoabs.81.s9.1","url":null,"abstract":"The genetics of pheochromocytoma and paraganglioma (PPGL) has become increasingly complex over the last two decades. The list of genes involved in the development of these tumors has grown steadily, and there are currently more than 20 driver genes implicated in either the hereditary or the sporadic nature of the disease. Although genetic diagnosis is achieved in about 75-80% of patients, the genetic aetiology remains unexplained in a significant percentage of cases. Patients lacking a genetic diagnosis include not only those with apparently sporadic PPGL, but also patients with a family history of the disease or with multiple tumors, that meet the criteria to be considered as candidates for carrying germline mutations in yet undiscovered genes. Mutations in known PPGL genes deregulate three main signaling pathways (hypoxia, kinase signaling and wnt-signaling pathways), which could be the starting point for the development of a personalised treatment for PPGL patients. Furthermore, the integration of results from several genomic high-throughput platforms enables the discovery of regulatory mechanisms that cannot be identified by analyzing each piece of information separately. These strategies are powerful tools for elucidating optimal therapeutic options based on molecular biomarkers in PPGL, and represent an important step towards the achievement of precision medicine for patients with metastatic PPGL.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43824128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 3

The Chd4 subunit of the NuRD complex regulates Pdx1-controlled genes involved in β-cell function. NuRD复合体的Chd4亚基调节参与β细胞功能的pdx1控制基因。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-05-01 DOI: 10.1530/JME-22-0011

Rebecca K Davidson, Staci A. Weaver, Nolan Casey, Sukrati Kanojia, Elise Hogarth, Rebecca Schneider Aguirre, E. Sims, C. Evans-Molina, Jason M Spaeth

{"title":"The Chd4 subunit of the NuRD complex regulates Pdx1-controlled genes involved in β-cell function.","authors":"Rebecca K Davidson, Staci A. Weaver, Nolan Casey, Sukrati Kanojia, Elise Hogarth, Rebecca Schneider Aguirre, E. Sims, C. Evans-Molina, Jason M Spaeth","doi":"10.1530/JME-22-0011","DOIUrl":"https://doi.org/10.1530/JME-22-0011","url":null,"abstract":"Type 2 diabetes (T2D) is associated with loss of transcription factors (TFs) from a subset of failing β-cells. Among these TFs is Pdx1, which controls the expression of numerous genes involved in maintaining β-cell function and identity. Pdx1 activity is modulated by transcriptional coregulators and has recently been shown, through an unbiased screen, to interact with the Chd4 ATPase subunit of the Nucleosome Remodeling and Deacetylase complex. Chd4 contributes to the maintenance of cellular identity and functional status of numerous different cell types. Here, we demonstrate Pdx1 dynamically interacts with Chd4 under physiological and stimulatory conditions within islet β-cells. We establish a fundamental role for Chd4 in regulating insulin secretion and modulating numerous Pdx1 bound genes in vitro, including the MafA TF, where we discovered Chd4 is bound at the MafA Region 3 enhancer. Furthermore, we found that Pdx1:Chd4 interactions are significantly compromised in islet β-cells under metabolically-induced stress in vivo and in human donor tissues with T2D. Our findings establish a fundamental role for Chd4 in regulating insulin secretion and modulating Pdx1-bound genes in vitro, and disruption of Pdx1:Chd4 interactions coincides with β-cell dysfunction associated with T2D.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43968059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 2

Liraglutide stimulates the β-catenin signaling cascade in mouse epididymal fat tissue. 利拉鲁肽刺激小鼠附睾脂肪组织中的β-连环蛋白信号级联反应。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-05-01 DOI: 10.1530/JME-22-0026

J. Gu, W. Shao, Di Liu, Jiajun Feng, Juan Pang, T. Jin

{"title":"Liraglutide stimulates the β-catenin signaling cascade in mouse epididymal fat tissue.","authors":"J. Gu, W. Shao, Di Liu, Jiajun Feng, Juan Pang, T. Jin","doi":"10.1530/JME-22-0026","DOIUrl":"https://doi.org/10.1530/JME-22-0026","url":null,"abstract":"Although canonical Wnt signaling pathway activation was shown to negatively regulate adipogenesis, recent investigations suggest that Wnt pathway effectors TCF7L2 and β-catenin (β-cat) in adipose tissues are also involved in energy homeostasis during adulthood. In assessing metabolic beneficial effect of GLP-1-based diabetes-drugs in high fat diet (HFD) challenged mice, we observed that liraglutide treatment affected expression of a battery of adipose tissue-specific genes, including that encode adiponectin and leptin, mainly in epididymal white adipose tissue (eWAT). Fourteen-week HFD challenge repressed TCF7L2 and β-cat S675 phosphorylation in eWAT while such repression was reversed by liraglutide treatment (150 µg/kg body weight daily) during week 10 to week 14. In Glp1r-/- mice, liraglutide failed in stimulating TCF7L2 or β-cat in eWAT. We detected Glp1r expression in mouse eWAT and its level is enriched in its \"stromal vascular fraction\" (SVF). Mouse eWAT-SVF showed reduced expression of Tcf7l2 and its Tcf7l2 level could not be stimulated by liraglutide treatment; while following adipogenic differentiation, rat eWAT-SVF showed elevated Tcf7l2 expression. Direct in vitro liraglutide treatment in eWAT-SVF stimulated CREB S133, β-cat S675 phosphorylation, and cellular cAMP level. Thus, cAMP/β-cat signaling cascade can be stimulated by liraglutide in eWAT via GLP-1R expressed in eWAT-SVF.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46397261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 3

Insights of the role of estrogen in obesity from two models of ERα deletion. 雌激素在两种ERα缺失模型中肥胖症中的作用

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-04-05 DOI: 10.1530/JME-21-0260

Rocío Del M Saavedra-Peña, Natalia Taylor, Matthew S Rodeheffer

{"title":"Insights of the role of estrogen in obesity from two models of ERα deletion.","authors":"Rocío Del M Saavedra-Peña, Natalia Taylor, Matthew S Rodeheffer","doi":"10.1530/JME-21-0260","DOIUrl":"10.1530/JME-21-0260","url":null,"abstract":"Sex hormones play a pivotal role in physiology and disease. Estrogen, the female sex hormone, has been long implicated in having protective roles against obesity. However, the direct impact of estrogens in white adipose tissue (WAT) function and growth is not understood. Here, we show that the deletion of estrogen receptor alpha (ERα; Esr1) from adipocytes using Adipoq-credoes not affect adipose mass in male or female mice under normal or high-fat diet (HFD) conditions. However, loss of ERα in adipocyte precursor cells (APs) via Pdgfra-cre leads to exacerbated obesity upon HFD feeding in both male and female mice, with s.c. adipose (SWAT)-specific expansion in male mice. Further characterization of these mice revealed infertility and increased plasma levels of sex hormones, including estradiol in female mice and androgens in male mice. These findings compromise the study of estrogen signaling within the adipocyte lineage using the Pdgfra-crestrain. However, AP transplant studies demonstrate that the increased AP hyperplasia in male SWAT upon Pdgfra-cre-mediated ablation of ERα is not driven by AP-intrinsic mechanisms but is rather mediated by off-target effects. These data highlight the inherent difficulties in studying models that disrupt the intricate balance of sex hormones. Thus, better approaches are needed to study the cellular and molecular mechanisms of sex hormones in obesity and disease.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"68 4","pages":"179-194"},"PeriodicalIF":3.5,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10173145/pdf/nihms-1887822.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9818152","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