Endocrinology最新文献_第4页

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 : 2025-03-24 DOI: 10.1210/endocr/bqaf068

引用次数: 0

Type 2 Deiodinase Promotes Fatty Adipogenesis in Muscle Fibroadipogenic Progenitors From Adult Male Mice. 2型脱碘酶促进成年雄性小鼠肌肉纤维脂肪祖细胞的脂肪脂肪生成。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf050

Cristina Luongo, Daniela Di Girolamo, Raffaele Ambrosio, Sara Di Cintio, Maria Angela De Stefano, Tommaso Porcelli, Domenico Salvatore

{"title":"Type 2 Deiodinase Promotes Fatty Adipogenesis in Muscle Fibroadipogenic Progenitors From Adult Male Mice.","authors":"Cristina Luongo, Daniela Di Girolamo, Raffaele Ambrosio, Sara Di Cintio, Maria Angela De Stefano, Tommaso Porcelli, Domenico Salvatore","doi":"10.1210/endocr/bqaf050","DOIUrl":"10.1210/endocr/bqaf050","url":null,"abstract":"Fibro-adipogenic progenitor cells (FAPs) are a heterogeneous population of multipotent mesenchymal cells that give rise to fibroblasts and adipocytes. In response to muscle injury, FAPs are activated and cooperate with inflammatory and muscle stem cells to promote muscle regeneration. In pathological conditions, such as muscular dystrophies, this coordinated response is partially lost and an accumulation of FAPs is observed that is responsible for maladaptive fibrosis, ectopic fat deposition, and impaired muscle regeneration. The role of intracellular thyroid hormone (TH) signaling in this cellular context is largely unknown. Here we show that intracellular 3,5,3'-triiodothyronine (T3) concentration in FAPs is increased in vitro during adipogenic differentiation via the increase of the T3-producing type 2 deiodinase (D2). The adipogenic potential is reduced in FAPs cultured in the presence of 3,3,5'-triiodothyronine (rT3), a specific D2 inhibitor, while exogenous administration of THs is able to induce the expression of relevant adipogenic genes. Accordingly, on genetic D2 depletion in vivo, adipogenesis was significantly reduced in D2KO compared to control mice. These data were confirmed using a FAP-inducible specific D2-KO mouse model, suggesting that a cell-specific D2-depletion in FAPs is sufficient to decrease fatty muscle infiltration and to improve muscle regeneration. Taken together, these data show that TH signaling is dynamically modulated in FAPs wherein D2-produced T3 is required to promote maturation of FAPs into adipocytes.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585151","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

Neurotensin Regulates Primate Ovulation Via Multiple Neurotensin Receptors. 神经紧张素通过多个神经紧张素受体调节灵长类动物排卵。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf041

Andrew C Pearson, Jessica S Miller, Hannah J Jensen, Ketan Shrestha, Thomas E Curry, Diane M Duffy

{"title":"Neurotensin Regulates Primate Ovulation Via Multiple Neurotensin Receptors.","authors":"Andrew C Pearson, Jessica S Miller, Hannah J Jensen, Ketan Shrestha, Thomas E Curry, Diane M Duffy","doi":"10.1210/endocr/bqaf041","DOIUrl":"10.1210/endocr/bqaf041","url":null,"abstract":"Neurotensin (NTS), a small neuropeptide, was recently established as a key paracrine mediator of ovulation. NTS mRNA is highly expressed by granulosa cells in response to the luteinizing hormone surge, and multiple NTS receptors are expressed by cells of the ovulatory follicle. To identify the role of NTS receptors NTSR1 and SORT1 in ovulation in vivo, the dominant follicle of cynomolgus macaques (Macaca fascicularis) was injected with either vehicle control, the general NTS receptor antagonist SR142948, the NTSR1-selective antagonist SR48692, or the SORT1-selective antagonist AF38469. hCG was then administered to initiate ovulatory events. Ovulation was successful in all control-injected follicles. Rupture sites were smaller or absent after injection with NTS receptor antagonists. Histological analysis of follicles injected with SR142948, SR48692, or AF38469 revealed increased red blood cell extravasation and pooling in the follicle antrum when compared to controls. NTS receptor antagonist-injected follicles also showed dysregulated capillary formation and reduced luteinization of the granulosa cell layer. Prior in vitro studies showed that NTS significantly increased monkey ovarian microvascular endothelial cell (mOMEC) migration, while decreasing monolayer permeability. The NSTR1 antagonist SR48692 or siRNA knockdown of NTSR1 abrogated the ability of NTS to stimulate mOMEC migration and to decrease monolayer permeability. Similar experiments performed with the SORT1 antagonist AF38469 or siRNA knockdown of SORT1 also resulted in ablation of NTS-mediated changes in migration and permeability after SORT1 signaling was impaired. Together, these data implicate both NTSR1 and SORT1 to be critical mediators of NTS-stimulated ovulation, luteinization, and angiogenesis of the ovulatory follicle.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556244","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

Renin Finds a New Target. Renin找到了一个新的目标。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf061

Willis K Samson, Gina L C Yosten

引用次数: 0

Correction to: "Ghrelin Promotes Functional Angiogenesis in a Mouse Model of Critical Limb Ischemia Through Activation of Proangiogenic MicroRNAs". 更正：“Ghrelin通过激活促血管生成microrna促进小鼠危急肢体缺血模型中的功能性血管生成”。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf044

引用次数: 0

Transgenerational Effects of the Obesogen Tributyltin on Metabolic Health in Mice: Interactions With a Western Diet. 肥胖原三丁基廷对小鼠代谢健康的跨代影响：与西方饮食的相互作用。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf063

Richard C Chang, Yikai Huang, Kaitlin To, Ryan Scott Whitlock, Katelyn Uyen Nguyen, Michelle Clara Joemon, Miranda Lopez, Kritin Guy Deeprompt, Toshi Shioda, Bruce Blumberg

{"title":"Transgenerational Effects of the Obesogen Tributyltin on Metabolic Health in Mice: Interactions With a Western Diet.","authors":"Richard C Chang, Yikai Huang, Kaitlin To, Ryan Scott Whitlock, Katelyn Uyen Nguyen, Michelle Clara Joemon, Miranda Lopez, Kritin Guy Deeprompt, Toshi Shioda, Bruce Blumberg","doi":"10.1210/endocr/bqaf063","DOIUrl":"10.1210/endocr/bqaf063","url":null,"abstract":"Obesity is a global health crisis, with increasing evidence linking environmental factors such as exposure to endocrine-disrupting chemicals (EDCs) to its development. This study examines the transgenerational effects of exposure to the model obesogen, tributyltin (TBT), on obesity and metabolic health, specifically focusing on how these effects interact with a diet modeling the 50th percentile of US dietary consumption [the Total Western Diet (TWD)]. Pregnant F0 dams were exposed to TBT, and their offspring were subjected at adulthood to different diets, including a high-fat diet and TWD, across multiple subsequent generations (F1-F3). We found that TBT exposure predisposed male offspring to increased fat accumulation, insulin resistance, and metabolic dysfunction, effects that were exacerbated by the TWD. Notably, male offspring displayed elevated leptin levels, hepatic fibrosis, and inflammatory responses under TWD exposure, suggesting an additive or synergistic relationship between obesogen exposure and dietary fat intake. These transgenerational effects were largely absent in female offspring, underscoring sex-specific vulnerabilities to environmental and dietary factors. Our results demonstrated that the combination of prenatal TBT exposure and TWD amplifies metabolic disturbances across generations, highlighting the need to consider both environmental chemicals and dietary patterns in addressing the obesity pandemic. This study underscores the critical role of early-life EDC exposures and dietary factors in shaping long-term metabolic health and the potential for transgenerational programming of susceptibility to obesity and metabolic disorders.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779395","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

Suppression of Luteinizing Hormone Secretion in Female Mice by a Urocortin 2-CRHR2 Signaling Pathway. 通过尿皮质素2 - CRHR2信号通路抑制雌性小鼠黄体生成素分泌。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf042

Richard B McCosh, Helen F Bell, Michael J Kreisman, Katherine Tian, Kellie M Breen

{"title":"Suppression of Luteinizing Hormone Secretion in Female Mice by a Urocortin 2-CRHR2 Signaling Pathway.","authors":"Richard B McCosh, Helen F Bell, Michael J Kreisman, Katherine Tian, Kellie M Breen","doi":"10.1210/endocr/bqaf042","DOIUrl":"10.1210/endocr/bqaf042","url":null,"abstract":"Physiologic stress elicits impairment of reproductive function, in part, by the suppression of luteinizing hormone (LH) secretion. Two populations of kisspeptin-synthesizing neurons in the hypothalamus play essential roles in controlling the pulsatile and surge modes of LH secretion and are potential direct targets of stress-activated neural circuits; however, the mechanism(s) for impairment of kisspeptin cells during stress remain unclear. Here, we conducted 4 experiments to test the hypothesis that corticotropin-releasing hormone receptor 2 (CRHR2) signaling contributes to impaired pulsatile and surge LH secretion via direct actions on kisspeptin cells. First, we observed that cells expressing a specific ligand of CRHR2, urocortin 2 (UCN2), show enhanced c-Fos in the paraventricular nucleus (PVN) following acute hypoglycemia, a metabolic stressor that rapidly suppresses LH pulses by impairing arcuate kisspeptin neuron activation. Second, we determined that central injection of UCN2 rapidly inhibits LH pulses. Furthermore, UCN2 disrupts evening expression of the estradiol-induced LH surge and reduces kisspeptin cell activation in the rostral periventricular hypothalamic region (RP3V). Next, we identified CRHR2 in a majority of both arcuate and RP3V kisspeptin cells. Finally, we observed that UCN2 cells in the PVN are activated following chemogenetic stimulation of catecholamine neurons in the nucleus of the solitary tract. Together these data demonstrate that UCN2-CRHR2 signaling disrupts the pulsatile and surge modes of LH secretion via direct suppression of kisspeptin cells. Furthermore, these findings suggest UCN2 cells in the PVN are regulated by metabolic stress and brainstem norepinephrine signaling pathways that convey stress cues to the hypothalamus.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556168","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

Evolution of the Complex Growth Hormone Gene Cluster in Macaques. 猕猴复杂生长激素基因簇的进化。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf056

Michael Wallis

{"title":"Evolution of the Complex Growth Hormone Gene Cluster in Macaques.","authors":"Michael Wallis","doi":"10.1210/endocr/bqaf056","DOIUrl":"10.1210/endocr/bqaf056","url":null,"abstract":"In higher primates, unlike other mammals, the GH gene locus is complex, comprising several GH-like genes, resulting from gene duplication and divergent evolution, expressed in pituitary and placenta. There are 5 genes in this GH gene cluster in human and 5 to 7 in apes and most Old-World monkeys, but in macaques the cluster has expanded further. Here the nature and evolution of the GH locus in this important primate genus is explored. Analysis of genomic data for Macaca fascicularis (crab-eating macaque) revealed that the GH gene cluster in this species is variable, with at least 5 different haplotypes, comprising 11 to 14 GH-like genes. Gene-number heterozygosity was also detected in Macaca mulatta (rhesus macaque) with 9 to 13 genes. Analysis of genomic data for other macaque species revealed GH gene clusters containing 8 to 14 GH-like genes, but gene-number heterozygosity was not detected. Expression of GH-like genes in pituitary and placenta was examined for Macaca fascicularis. This analysis has established that the complexity of the GH gene cluster increased during the evolution of macaques, by gene duplication and divergent evolution, and that these processes continue within at least 2 extant species. Analysis of rate of sequence change, and distribution of substitutions within the 3D structure, shows that for at least 1 GH-like gene (GH2), the changes reflect positive selection, implying adaptive biological change. Whether this involves changes in physiological (endocrine) function or response to viral or other pathogenic challenge is not yet clear.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656542","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

Impact of Excess Activin A on the Lipids, Metabolites, and Steroids of Adult Mouse Reproductive Organs. 过量激活素A对成年小鼠生殖器官脂质、代谢物和类固醇的影响。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf054

Jennifer C Hutchison, Paul J Trim, Penny A F Whiley, David J Handelsman, Marten F Snel, Nigel P Groome, Mark P Hedger, Kate L Loveland

{"title":"Impact of Excess Activin A on the Lipids, Metabolites, and Steroids of Adult Mouse Reproductive Organs.","authors":"Jennifer C Hutchison, Paul J Trim, Penny A F Whiley, David J Handelsman, Marten F Snel, Nigel P Groome, Mark P Hedger, Kate L Loveland","doi":"10.1210/endocr/bqaf054","DOIUrl":"https://doi.org/10.1210/endocr/bqaf054","url":null,"abstract":"Bioactivity of the hormone and growth factor activin A is central to fertility and health. Dysregulated circulating activin levels occur with medication usage and multiple pathological conditions. The inhibin-alpha knockout mouse (InhaKO) models chronic activin elevation and unopposed activin A bioactivity. In InhaKO fetal testes, lipid droplet, steroid profiles, and seminiferous cords are abnormal; adults develop gonadal and adrenal tumors due to chronic activin A excess exposure. Here we address how this exposure affects lipid, metabolite, and steroid composition in whole testes, ovaries, and adrenals of adult InhaKO mice using histological, transcriptomic, and mass spectrometry (MS) methods, including MS imaging (matrix-assisted laser desorption/ionization-MS imaging). Matrix-assisted laser desorption/ionization-MS imaging delineated spatial lipid profiles within interstitial, inner cord, and outer cord regions containing normal spermatogenesis; these differed between wild-type and KO samples. In proximity to tumors, lipids showed distinctive distribution patterns both within and adjacent to the tumor. Significantly altered lipids and metabolic profiles in whole InhaKO testes homogenates were linked to energy-related pathways. In gonads and adrenal glands of both sexes, steroidogenic enzyme transcription, and steroids are different, as expected. Lipid profiles and steroidogenic enzyme proteins, HSD3B1 and CYP11A1, are affected within and near gonadal tumors. This documents organ-specific effects of chronic activin A elevation on lipid composition and cellular metabolism, in both histologically normal and tumor-affected areas. The potential for activin A to influence numerous steroidogenic processes should be considered in context and with spatial precision, particularly in relationship to pathologies.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":"166 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992821","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

Target Discovery to Diabetes Therapy-TXNIP From Bench to Bedside With NIDDK. 糖尿病治疗靶点的发现- TXNIP从实验室到床边与NIDDK。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf055

Anath Shalev

{"title":"Target Discovery to Diabetes Therapy-TXNIP From Bench to Bedside With NIDDK.","authors":"Anath Shalev","doi":"10.1210/endocr/bqaf055","DOIUrl":"10.1210/endocr/bqaf055","url":null,"abstract":"Diabetes is the most expensive chronic disease in the United States, with more than $400 billion in annual costs, and it affects more than 38 million Americans. While major advances in drug treatment have been made for type 2 diabetes (T2D) and the often-associated obesity, there are still no approved and effective medications targeting β-cell loss or islet dysfunction, which is one of the major underlying causes of both type 1 diabetes (T1D) and T2D. In addition, there are no oral medications for T1D approved in the United States more than 100 years after the discovery of insulin, and attractive therapeutic targets are only starting to emerge. As we celebrate the 75th anniversary of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), progress is finally being made in this area with NIDDK support. This mini-review follows the discovery of thioredoxin-interacting protein inhibitors as an example of a methodical approach to identify and develop an oral β-cell treatment for T1D. It further discusses how the initial molecular findings were translated into novel clinical treatment approaches that promote the patient's own islet health and β-cell function using drug repurposing as well as new drug discovery.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656545","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