Endocrinology最新文献_第4页

ZEB1 Inhibits LHβ Subunit Transcription When Overexpressed, but Is Dispensable for LH Synthesis in Mice. ZEB1 过度表达时会抑制 LHβ 亚基的转录，但在小鼠体内对 LH 的合成没有作用。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-08-27 DOI: 10.1210/endocr/bqae116

Hailey Schultz, Xiang Zhou, Carlos Agustín Isidro Alonso, Luisina Ongaro, Yeu-Farn Lin, Mary Loka, Thomas Brabletz, Simone Brabletz, Marc P Stemmler, Ulrich Boehm, Daniel J Bernard

{"title":"ZEB1 Inhibits LHβ Subunit Transcription When Overexpressed, but Is Dispensable for LH Synthesis in Mice.","authors":"Hailey Schultz, Xiang Zhou, Carlos Agustín Isidro Alonso, Luisina Ongaro, Yeu-Farn Lin, Mary Loka, Thomas Brabletz, Simone Brabletz, Marc P Stemmler, Ulrich Boehm, Daniel J Bernard","doi":"10.1210/endocr/bqae116","DOIUrl":"10.1210/endocr/bqae116","url":null,"abstract":"Luteinizing hormone (LH), a heterodimeric glycoprotein produced by pituitary gonadotrope cells, regulates gonadal function. Hypothalamic gonadotropin-releasing hormone (GnRH) stimulates LH synthesis and secretion. GnRH induces LHβ subunit (Lhb) expression via the transcription factor, early growth response 1 (EGR1), acting on the Lhb promoter. In contrast, overexpression of zinc finger E-box binding homeobox 1 (ZEB1) represses LH production in mice, but the underlying mechanism was not previously elucidated. Here, we observed that ZEB1 inhibited GnRH-stimulated but not basal Lhb mRNA expression in homologous murine LβT2 cells. Moreover, ZEB1 blocked GnRH and/or EGR1 induction of murine Lhb but not human LHB promoter-reporter activity in these cells. Using chimeric reporters, we mapped the species-specific ZEB1 sensitivity to sequence differences, including in Z- and E-boxes, in the proximal Lhb/LHB promoters, immediately upstream of the transcription start sites. ZEB1 bound to the murine Lhb promoter with higher affinity than to the human LHB promoter in this region. To examine ZEB1's physiological role in LH synthesis, we characterized gonadotrope-specific Zeb1 knockout mice. Loss of ZEB1 in gonadotropes did not affect LH production or secretion. Collectively, the data suggest that ZEB1, when overexpressed, can inhibit GnRH/EGR1 induction of murine Lhb transcription but does not play a necessary role in LH synthesis in mice.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153403","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

Androgen Receptors in GABA Neurons Are Required for Increased GABAergic Input to GnRH Neurons but not PCOS Symptoms. GABA 神经元中的雄激素受体是增加 GnRH 神经元 GABA 能输入的必要条件，但不是 PCOS 症状的必要条件。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-08-27 DOI: 10.1210/endocr/bqae105

Raphael E Szawka, Ana C Campideli-Santana

引用次数: 0

Long-term Metabolic Dysfunction Programming in Female Mice by Serial Moderate Restriction of a High-fat High-sucrose Diet. 连续适度限制高脂肪高蔗糖饮食对雌性小鼠代谢功能的长期影响

IF 3.8 3区医学

Endocrinology Pub Date : 2024-08-27 DOI: 10.1210/endocr/bqae117

Micah P Wildes, Deemantha G Fernando, Connie C Grobe, John J Reho, Justin L Grobe, Srividya Kidambi, Tammy L Kindel, Anne E Kwitek, Jeffrey L Segar, Joni S Williams, Lisa L Morselli

{"title":"Long-term Metabolic Dysfunction Programming in Female Mice by Serial Moderate Restriction of a High-fat High-sucrose Diet.","authors":"Micah P Wildes, Deemantha G Fernando, Connie C Grobe, John J Reho, Justin L Grobe, Srividya Kidambi, Tammy L Kindel, Anne E Kwitek, Jeffrey L Segar, Joni S Williams, Lisa L Morselli","doi":"10.1210/endocr/bqae117","DOIUrl":"10.1210/endocr/bqae117","url":null,"abstract":"Background: While intermittent fasting leads to weight loss and improved glucose metabolism, food insecurity, the insufficient access to food for a healthy life, is associated with obesity and adverse cardiometabolic health, especially in women. We aimed to characterize the effects of intermittently restricted feeding on energy balance and glucose tolerance in female mice.Methods: Female C57BL/6J mice were fed a high-fat, high-sucrose diet and intermittently food restricted to 60% of control littermates' ad libitum intake, starting at weaning and until week 19. Restricted mice were subsequently allowed ad libitum access to the same diet. Body composition and energy balance were measured at weeks 18.5, 19, 30, and 40. At week 42, mice underwent an intraperitoneal glucose tolerance test and plasma appetitive hormones measurements after nutrient gavage.Results: During the food restriction phase, restricted mice accrued lower weight and fat mass than controls despite periodic ad libitum food access. Reintroduction of continuous ad libitum food caused increased food intake during the light phase and increased body mass in restricted mice. Minor differences in body composition-adjusted energy expenditure between groups were observed at week 40. At week 42, glucose tolerance was impaired in restricted mice compared to controls, and trends toward lower levels of postprandial anorexigenic hormones glucagon-like peptide-1 and pancreatic polypeptide were observed.Conclusion: Our findings suggest that repeated intermittent food restriction leads to changes in eating behavior that predispose to glucose intolerance when food is freely available. Future studies are needed to elucidate the specific mechanisms underlying these changes.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11408931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139621","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

Nuclear Receptor Corepressors NCOR1 and SMRT Regulate Metabolism via Intestinal Regulation of Carbohydrate Transport. 核受体核心抑制因子 NCOR1 和 SMRT 通过肠道调节碳水化合物转运调节新陈代谢

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae100

Megan J Ritter, Izuki Amano, Anne H van der Spek, Adam C Gower, Hendrik J Undeutsch, Victor A P Rodrigues, Hanix E Daniel, Anthony N Hollenberg

{"title":"Nuclear Receptor Corepressors NCOR1 and SMRT Regulate Metabolism via Intestinal Regulation of Carbohydrate Transport.","authors":"Megan J Ritter, Izuki Amano, Anne H van der Spek, Adam C Gower, Hendrik J Undeutsch, Victor A P Rodrigues, Hanix E Daniel, Anthony N Hollenberg","doi":"10.1210/endocr/bqae100","DOIUrl":"10.1210/endocr/bqae100","url":null,"abstract":"Nuclear receptor action is mediated in part by the nuclear receptor corepressor 1 (NCOR1) and the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT). NCOR1 and SMRT regulate metabolic pathways that govern body mass, insulin sensitivity, and energy expenditure, representing an understudied area in the realm of metabolic health and disease. Previously, we found that NCOR1 and SMRT are essential for maintaining metabolic homeostasis and their knockout (KO) leads to rapid weight loss and hypoglycemia, which is not survivable. Because of a potential defect in glucose absorption, we sought to determine the role of NCOR1 and SMRT specifically in intestinal epithelial cells (IECs). We used a postnatal strategy to disrupt NCOR1 and SMRT throughout IECs in adult mice. These mice were characterized metabolically and underwent metabolic phenotyping, body composition analysis, and glucose tolerance testing. Jejunal IECs were isolated and profiled by bulk RNA sequencing. We found that the postnatal KO of NCOR1 and SMRT from IECs leads to rapid weight loss and hypoglycemia with a significant reduction in survival. This was accompanied by alterations in glucose metabolism and activation of fatty acid oxidation in IECs. Metabolic phenotyping confirmed a reduction in body mass driven by a loss of body fat without altered food intake. This appeared to be mediated by a reduction of key intestinal carbohydrate transporters, including SGLT1, GLUT2, and GLUT5. Intestinal NCOR1 and SMRT act in tandem to regulate glucose levels and body weight. This in part may be mediated by regulation of intestinal carbohydrate transporters.","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/PMC11337007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897150","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

Thyroid Hormone Receptors Function in GABAergic Neurons During Development and in Adults. 甲状腺激素受体在 GABA 能神经元的发育过程中和成年后发挥作用。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae101

Frédéric Flamant, Sabine Richard

引用次数: 0

Letter to the Editor From Hoekstra: "Adrenal Abcg1 Controls Cholesterol Flux and Steroidogenesis". Hoekstra 致编辑的信：《肾上腺 Abcg1 控制胆固醇通量和类固醇生成》。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae097

Menno Hoekstra

引用次数: 0

The Role of Prolactin in Amniotic Membrane Regeneration: Therapeutic Potential for Premature Rupture of Membranes. 催乳素在羊膜再生中的作用：胎膜早破的治疗潜力。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae095

Deqi Kong, Heeryun Cho, Soowon Hwang, Ahyoung Lee, Uk Lee, Yun-Bae Kim, Dong Ho Geum, Byung-Soo Kim, Young Mi Jung, Ho Yeon Kim, Geum Joon Cho, Kihoon Ahn, Min-Jeong Oh, Hai-Joong Kim, Hee Young Cho, Joong Shin Park, SoonCheol Hong

{"title":"The Role of Prolactin in Amniotic Membrane Regeneration: Therapeutic Potential for Premature Rupture of Membranes.","authors":"Deqi Kong, Heeryun Cho, Soowon Hwang, Ahyoung Lee, Uk Lee, Yun-Bae Kim, Dong Ho Geum, Byung-Soo Kim, Young Mi Jung, Ho Yeon Kim, Geum Joon Cho, Kihoon Ahn, Min-Jeong Oh, Hai-Joong Kim, Hee Young Cho, Joong Shin Park, SoonCheol Hong","doi":"10.1210/endocr/bqae095","DOIUrl":"10.1210/endocr/bqae095","url":null,"abstract":"Premature rupture of membranes (PROM) is defined as rupture of fetal membranes before the onset of labor. Prolactin (PRL) is secreted by decidual membranes and accumulated significantly in the amniotic fluid during pregnancy. PRL could ameliorate inflammation and collagen degradation in fetal membranes. However, the role of PRL in amniotic membrane is not well characterized. We isolated human amniotic epithelial stem cells (hAESCs) from human fetal membranes to study the effect of PRL on proliferation, migration, and antioxidative stress. Amniotic pore culture technique (APCT) model was constructed to evaluate the tissue regeneration effect in vitro. The potential targets and pathways of PRL acting in amnion via integrated bioinformatic methods. PRL had a dose-dependent effect on hAESCs in vitro. PRL (500 ng/mL) significantly improved the viability of hAESCs and inhibited cell apoptosis, related to the upregulation of CCN2 expression and downregulation of Bax, Caspase 3, and Caspase 8. PRL accelerated migration process in hAESCs via downregulation of MMP2, MMP3, and MMP9. PRL attenuated the cellular damage and mitochondrial dysfunction induced by hydrogen peroxide in hAESCs. PRL accelerated the healing process in the APCT model significantly. The top 10 specific targets (IGF1R, SIRT1, MAP2K1, CASP8, MAPK14, MCL1, NFKB1, HIF1A, MTOR, and HSP90AA1) and signaling pathways (such as HIF signaling pathway) were selected using an integrated bioinformatics approach. PRL improves the viability and antioxidative stress function of hAESCs and the regeneration of ruptured amniotic membranes in vitro. Thus, PRL has great therapeutic potential for prevention and treatment of ruptured membranes.","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":"141855163","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

Changes in the Bile Acid Pool and Timing of Female Puberty: Potential Novel Role of Hypothalamic TGR5. 胆汁酸库的变化与女性青春期的时间：下丘脑 TGR5 的潜在新作用。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae098

Heidi Vanden Brink, Doris Vandeputte, Ilana L Brito, Oline K Ronnekleiv, Mark S Roberson, Alejandro Lomniczi

{"title":"Changes in the Bile Acid Pool and Timing of Female Puberty: Potential Novel Role of Hypothalamic TGR5.","authors":"Heidi Vanden Brink, Doris Vandeputte, Ilana L Brito, Oline K Ronnekleiv, Mark S Roberson, Alejandro Lomniczi","doi":"10.1210/endocr/bqae098","DOIUrl":"10.1210/endocr/bqae098","url":null,"abstract":"Context: The regulation of pubertal timing and reproductive axis maturation is influenced by a myriad of physiologic and environmental inputs yet remains incompletely understood.Objective: To contrast differences in bile acid isoform profiles across defined stages of reproductive maturity in humans and a rat model of puberty and to characterize the role of bile acid signaling via hypothalamic expression of bile acid receptor populations in the rodent model.Methods: Secondary analysis and pilot studies of clinical cohorts, rodent models, ex vivo analyses of rodent hypothalamic tissues. Bile acid concentrations is the main outcome measure.Results: Lower circulatory conjugated:deconjugated bile acid concentrations and higher total secondary bile acids were observed in postmenarcheal vs pre-/early pubertal adolescents, with similar shifts observed in infantile (postnatal day [PN]14) vs early juvenile (PN21) rats alongside increased tgr5 receptor mRNA expression within the mediobasal hypothalamus of female rats. 16S rRNA gene sequencing of the rodent gut microbiome across postnatal life revealed changes in the gut microbial composition predicted to have bile salt hydrolase activity, which was observed in parallel with the increased deconjugated and increased concentrations of secondary bile acids. We show that TGR5-stimulated GnRH release from hypothalamic explants is mediated through kisspeptin receptors and that early overexpression of human-TGR5 within the arcuate nucleus accelerates pubertal onset in female rats.Conclusion: Bile acid isoform shifts along stages of reproductive maturation are conserved across rodents and humans, with preclinical models providing mechanistic insight for the neuroendocrine-hepatic-gut microbiome axis as a potential moderator of pubertal timing in females.","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/PMC11334072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855162","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

Progesterone Receptor Signaling Promotes Cancer Associated Fibroblast Mediated Tumorigenicity in ER+ Breast Cancer. 孕酮受体信号促进ER+乳腺癌中癌症相关成纤维细胞介导的致瘤性

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae092

Caroline H Diep, Angela Spartz, Thu H Truong, Amy R Dwyer, Dorraya El-Ashry, Carol A Lange

{"title":"Progesterone Receptor Signaling Promotes Cancer Associated Fibroblast Mediated Tumorigenicity in ER+ Breast Cancer.","authors":"Caroline H Diep, Angela Spartz, Thu H Truong, Amy R Dwyer, Dorraya El-Ashry, Carol A Lange","doi":"10.1210/endocr/bqae092","DOIUrl":"10.1210/endocr/bqae092","url":null,"abstract":"Breast cancer progression involves intricate interactions between cancer cells and the tumor microenvironment (TME). This study elucidates the critical role of progesterone receptor (PR) signaling in mediating the protumorigenic effects of cancer-associated fibroblasts (CAFs) on estrogen receptor-positive (ER+) luminal breast cancer cells. We demonstrate that CAFs produce physiologically relevant levels of estrogen and progesterone, which significantly contribute to breast cancer tumorigenicity. Specifically, CAF conditioned media (CM) promoted PR-dependent anchorage-independent growth, tumorsphere formation/stem cell expansion, and CD44 upregulation. CAF cells formed co-clusters more frequently with PR+ breast cancer cells relative to PR-null models. While both PR isoforms mediated these actions, PR-A was a dominant driver of tumorsphere formation/stemness, while PR-B induced robust CD44 expression and CAF/tumor cell co-cluster formation. CD44 knockdown impaired CAF/tumor cell co-clustering. Fibroblast growth factor 2 (FGF2), also secreted by CAFs, phosphorylated PR (Ser294) in a MAPK-dependent manner and activated PR to enhance CD44 expression and breast cancer tumorigenicity. The FGF receptor (FGFR) inhibitor PD173074 diminished CAF- and FGF2-dependent PR activation, tumorsphere formation, and co-clustering. In summary, this study reveals a novel mechanism through which stromal CAFs orchestrate elevated PR signaling in ER+ luminal breast cancer via secretion of both progesterone and FGF2, a potent activator of ERK1/2. Understanding tumor cell/TME interactions provides insights into potential therapeutic strategies aimed at disrupting PR- and/or FGF2/FGFR-dependent signaling pathways to prevent early metastasis in patients with ER+ breast cancer.","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":"141747792","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

Pituitary Complications of Checkpoint Inhibitor Use. 使用检查点抑制剂的垂体并发症。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-07-26 DOI: 10.1210/endocr/bqae084

Natalia Chamorro-Pareja, Alexander T Faje, Karen K Miller

引用次数: 0