Endocrinology最新文献_第10页

Thyroid Hormone Regulates Postnatal Development of the Rete Testis in Mice. 甲状腺激素调节小鼠睾丸的产后发育

IF 3.8 3区医学

Endocrinology Pub Date : 2024-09-26 DOI: 10.1210/endocr/bqae125

Andrey Yu Kulibin, Ekaterina A Malolina

引用次数: 0

Relaxin Modulates the Genomic Actions and Biological Effects of Estrogen in the Myometrium. 松弛素调节子宫肌瘤中雌激素的基因组作用和生物效应

IF 3.8 3区医学

Endocrinology Pub Date : 2024-09-26 DOI: 10.1210/endocr/bqae123

Sudeshna Tripathy, Anusha Nagari, Shu-Ping Chiu, Tulip Nandu, Cristel V Camacho, Mala Mahendroo, W Lee Kraus

{"title":"Relaxin Modulates the Genomic Actions and Biological Effects of Estrogen in the Myometrium.","authors":"Sudeshna Tripathy, Anusha Nagari, Shu-Ping Chiu, Tulip Nandu, Cristel V Camacho, Mala Mahendroo, W Lee Kraus","doi":"10.1210/endocr/bqae123","DOIUrl":"10.1210/endocr/bqae123","url":null,"abstract":"Estradiol (E2) and relaxin (Rln) are steroid and polypeptide hormones, respectively, with important roles in the female reproductive tract, including myometrium. Some actions of Rln, which are mediated by its membrane receptor RXFP1, require or are augmented by E2 signaling through its cognate nuclear steroid receptor, estrogen receptor alpha (ERα). In contrast, other actions of Rln act in opposition to the effects of E2. Here we explored the molecular and genomic mechanisms that underlie the functional interplay between E2 and Rln in the myometrium. We used both ovariectomized female mice and immortalized human myometrial cells expressing wild-type or mutant ERα (hTERT-HM-ERα cells). Our results indicate that Rln modulates the genomic actions and biological effects of estrogen in the myometrium and myometrial cells by reducing phosphorylation of ERα on serine 118 (S118), as well as by reducing the E2-dependent binding of ERα across the genome. These effects were associated with changes in the hormone-regulated transcriptome, including a decrease in the E2-dependent expression of some genes and enhanced expression of others. The inhibitory effects of Rln cotreatment on the E2-dependent phosphorylation of ERα required the nuclear dual-specificity phosphatases DUSP1 and DUSP5. Moreover, the inhibitory effects of Rln were reflected in a concomitant inhibition of the E2-dependent contraction of myometrial cells. Collectively, our results identify a pathway that integrates Rln/RXFP1 and E2/ERα signaling, resulting in a convergence of membrane and nuclear signaling pathways to control genomic and biological outcomes.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282312","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

Neuregulin 1 Signaling Attenuates Tumor Necrosis Factor α-Induced Female Rat Luteal Cell Death. Neuregulin 1 信号传导可减轻肿瘤坏死因子-α诱导的雌性大鼠黄体细胞死亡。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-09-26 DOI: 10.1210/endocr/bqae129

Saswati Banerjee, Babayewa Oguljahan, Winston E Thompson, Indrajit Chowdhury

{"title":"Neuregulin 1 Signaling Attenuates Tumor Necrosis Factor α-Induced Female Rat Luteal Cell Death.","authors":"Saswati Banerjee, Babayewa Oguljahan, Winston E Thompson, Indrajit Chowdhury","doi":"10.1210/endocr/bqae129","DOIUrl":"10.1210/endocr/bqae129","url":null,"abstract":"The corpus luteum (CL) is a transient ovarian endocrine structure that maintains pregnancy in primates during the first trimester and in rodents during the entire pregnancy by producing steroid hormone progesterone (P4). CL lifespan, growth, and differentiation are tightly regulated by survival and cell death signals through luteotrophic and luteolytic factors, including the epidermal growth factor (EGF)-like factor family. Neuregulin 1 (NRG1), a member of the EGF family, mediates its effect through ErbB2/3 receptors. However, the functional role of NRG1 in luteal cells (LCs) is unknown. Thus, this study investigated the role of NRG1 and its molecular mechanism of action in rat LC. Our experimental results suggest a strong positive correlation between steroidogenic acute regulatory protein (StAR) and NRG1 expression in mid-CL and serum P4 and estrogen (E2) production. In contrast, there was a decrease in StAR and NRG1 expression and P4 and E2 production with an increase in tumor necrosis factor α (TNFα) expression in regressing CL. Further in vitro studies in LCs showed that the knockdown of endogenous Nrg1 promoted the expression of proinflammatory and proapoptotic factors and decreased prosurvival factor expression. Subsequently, treatment with exogenous TNFα under these experimental conditions profoundly elevated proinflammatory and proapoptotic factors. Further analysis demonstrated that the phosphorylation status of ErbB2/3, PI3K, Ak strain transforming or protein kinase B (Akt), and ErK1/2 was significantly inhibited under these experimental conditions, whereas the treatment of TNFα further inhibited the phosphorylation of ErbB2/3, PI3K, Akt, and ErK1/2. Collectively, these studies provide new insights into the NRG1-mediated immunomodulatory and prosurvival role in LCs, which may maintain the function of CL.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307439","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

In Vivo Contribution of Cyp24a1 Promoter Vitamin D Response Elements. Cyp24a1 启动子维生素 D 反应元件的体内贡献。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-09-26 DOI: 10.1210/endocr/bqae134

Mark B Meyer, Seong Min Lee, Jordan M Towne, Shannon R Cichanski, Martin Kaufmann, Glenville Jones, J Wesley Pike

{"title":"In Vivo Contribution of Cyp24a1 Promoter Vitamin D Response Elements.","authors":"Mark B Meyer, Seong Min Lee, Jordan M Towne, Shannon R Cichanski, Martin Kaufmann, Glenville Jones, J Wesley Pike","doi":"10.1210/endocr/bqae134","DOIUrl":"10.1210/endocr/bqae134","url":null,"abstract":"CYP24A1 is a multifunctional, P450 mitochondrial enzyme that catabolizes the vitamin D hormone (calcitriol, 1,25(OH)2D3), its precursor (calcifediol, 25(OH)D3), and numerous vitamin D metabolites. In the kidney, Cyp24a1 is induced by 1,25(OH)2D3 and fibroblast growth factor 23 (FGF23) and potently suppressed by PTH to control the circulating levels of 1,25(OH)2D3. Cyp24a1 is controlled by a pair of promoter proximal (PRO) vitamin D response elements (VDREs) that are aided by distal, downstream (DS) enhancers. The downstream 1 region of Cyp24a1 (DS1) enhancer is kidney-specific and responsible for PTH and FGF23 actions, and the downstream 2 region of Cyp24a1 enhancer responds to 1,25(OH)2D3 in all tissues. Despite this knowledge, in vivo contributions of the PRO VDREs to basal expression, FGF23 activation, and PTH suppression of Cyp24a1 remain unknown. In this study, we selectively mutated the PRO VDREs in the mouse to address these questions. We found mutation of the VDREs leads to a dramatic loss of VDR occupancy, a reduction of 1,25(OH)D3-induced kidney Cyp24a1 expression, and near elimination of intestinal Cyp24a1 induction. FGF23 induction of Cyp24a1 was reduced but not eliminated and still showed a synergistic increase with 1,25(OH)2D3. PTH suppression of Cyp24a1 was unchanged, despite minor reductions in total for phosphorylated cAMP-response element binding protein occupancy. Finally, VDR recruitment was dramatically reduced across the DS enhancers in the Cyp24a1 locus. Taken together, our data suggest a cooperative relationship between the DS and PRO enhancers in the regulation of Cyp24a1 by 1,25(OH)2D3 and FGF23 and points to the DS1 region as a crucial basal switch for Cyp24a1 activity that further defines the interconnected genomic control in vitamin D catabolism.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371250","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

Correction to: "Thyroid Hormone Receptors Function in GABAergic Neurons During Development and in Adults". 更正："甲状腺激素受体在 GABA 能神经元发育过程中和成年后的功能"。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-09-26 DOI: 10.1210/endocr/bqae138

引用次数: 0

Circadian regulatory networks of glucose homeostasis and its disruption as a potential cause of under-nutrition. 葡萄糖平衡的昼夜节律调控网络及其作为营养不良潜在原因的破坏。

IF 4.8 3区医学

Endocrinology Pub Date : 2024-09-14 DOI: 10.1210/endocr/bqae126

Shinsuke Onuma,Masanobu Kawai

{"title":"Circadian regulatory networks of glucose homeostasis and its disruption as a potential cause of under-nutrition.","authors":"Shinsuke Onuma,Masanobu Kawai","doi":"10.1210/endocr/bqae126","DOIUrl":"https://doi.org/10.1210/endocr/bqae126","url":null,"abstract":"The circadian clock system, an evolutionarily conserved mechanism, orchestrates diurnal rhythms in biological activities such as behavior and metabolism, aligning them with the earth's 24-hour light/dark cycle. This synchronization enables organisms to anticipate and adapt to predictable environmental changes, including nutrient availability. However, modern lifestyles characterized by irregular eating and sleeping habits disrupt this synchrony, leading to metabolic disorders such as obesity and metabolic syndrome, evidenced by higher obesity rates among shift workers. Conversely, circadian disturbances are also associated with reduced nutrient absorption and an increased risk of malnutrition in populations such as the critically ill or the elderly. The precise mechanisms of these disturbances in leading to either over-nutrition or under-nutrition is complex and not yet fully understood. Glucose, a crucial energy source, is closely linked to obesity when consumed excessively and to weight loss when intake is reduced, which suggests that circadian regulation of glucose metabolism is a key factor connecting circadian disturbances with nutritional outcomes. In this review, we describe how the biological clock in various tissues regulates glucose metabolism, with a primary focus on studies utilizing animal models. Additionally, we highlight current clinical evidence supporting the association between circadian disturbance and glucose metabolism, arguing that such disruption could predominantly contribute to under-nutrition due to impaired efficient utilization of nutrients.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":"40 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251692","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

Thyroid Hormone and Alzheimer's: Bridging Epidemiology to Mechanism. 甲状腺激素与阿尔茨海默氏症：从流行病学到机理的桥梁

IF 4.8 3区医学

Endocrinology Pub Date : 2024-09-14 DOI: 10.1210/endocr/bqae124

Sergio Escamilla,Federico Salas-Lucia

{"title":"Thyroid Hormone and Alzheimer's: Bridging Epidemiology to Mechanism.","authors":"Sergio Escamilla,Federico Salas-Lucia","doi":"10.1210/endocr/bqae124","DOIUrl":"https://doi.org/10.1210/endocr/bqae124","url":null,"abstract":"The identification of critical factors that can worsen the mechanisms contributing to the pathophysiology of Alzheimer's is paramount. Thyroid hormones (TH) fit this criterion. Epidemiological studies have identified an association between altered circulating TH levels and Alzheimer's. The study of human and animal models indicates that TH can affect all the main cellular, molecular, and genetic mechanisms known as hallmarks of Alzheimer's. This is true not only for the excessive production in the brain of protein aggregates leading to amyloid plaques and neurofibrillary tangles but also for the clearance of these molecules from the brain parenchyma via the blood-brain barrier and for the escalated process of neuroinflammation-and even for the effects of carrying Alzheimer's-associated genetic variants. Suboptimal TH levels result in a greater accumulation of protein aggregates in the brain. The direct TH regulation of critical genes involved in amyloid beta production and clearance is remarkable, affecting the expression of multiple genes, including APP (related to amyloid beta production), APOE, LRP1, TREM2, AQP4, and ABCB1 (related to amyloid beta clearance). TH also affects microglia by increasing their migration and function and directly regulating the immunosuppressor gene CD73, impacting the immune response of these cells. Studies aiming to understand the mechanisms that could explain how changes in TH levels can contribute to the brain alterations seen in patients with Alzheimer's are ongoing. These studies have potential implications for the management of patients with Alzheimer's and ultimately can contribute to devising new interventions for these conditions.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":"6 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251734","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

Ex-CyT-ing Applications of Single-Cell CyTOF to Human Pancreatic Islets in Diabetes Research. 单细胞 CyTOF 在糖尿病研究中的 Ex-CyT-ing 应用。

IF 4.8 3区医学

Endocrinology Pub Date : 2024-09-14 DOI: 10.1210/endocr/bqae122

Kathryn E Glorioso,Jennifer S Stancill

引用次数: 0

The deletion of nuclear progesterone receptors from kisspeptin cells does not impair negative feedback in female mice. 从kisspeptin细胞中删除核孕酮受体不会损害雌性小鼠的负反馈。

IF 4.8 3区医学

Endocrinology Pub Date : 2024-09-10 DOI: 10.1210/endocr/bqae121

Kendra M Dillon,Dayanara B Lohr,Alyssa G Novak,Anna-Maria V Petriv,Nicole T Neifert,Aleisha M Moore

{"title":"The deletion of nuclear progesterone receptors from kisspeptin cells does not impair negative feedback in female mice.","authors":"Kendra M Dillon,Dayanara B Lohr,Alyssa G Novak,Anna-Maria V Petriv,Nicole T Neifert,Aleisha M Moore","doi":"10.1210/endocr/bqae121","DOIUrl":"https://doi.org/10.1210/endocr/bqae121","url":null,"abstract":"Reproductive function in mammals depends on the ability of progesterone to suppress pulsatile gonadotrophin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion in a homeostatic negative feedback loop. Previous research identified that cells upstream from GnRH neurons expressing the nuclear progesterone receptor (PGR) are required for progesterone-negative feedback. However, the identity of these cells and the mechanism by which they reduce GnRH/LH pulsatile secretion is unknown. We aimed to address the hypothesis that PGR expressed by a neural population in the arcuate nucleus recently identified as the GnRH pulse generator, cells expressing Kisspeptin, Neurokinin B, and Dynorphin (KNDy cells), mediate progesterone negative feedback. To achieve this, we utilized female mice with the PGR gene conditionally deleted from kisspeptin cells (KPRKO mice) and observed a substantial decrease in the percentage of KNDy neurons co-expressing PGR mRNA (11% in KPRKO mice versus 86% in wildtype mice). However, KPRKO mice did not display changes in the frequency or amplitude of LH pulses in diestrus or estrus, nor in the ability of exogenous progesterone to blunt a post-castration rise in LH. Further, mRNA expression of arcuate kisspeptin and dynorphin, which are excitatory and inhibitory to GnRH secretion, respectively, remained unaltered in KPRKO mice compared to wildtype controls. Together, these findings show that the near-complete loss of PGR signaling from KNDy cells does not impact negative feedback regulation of GnRH pulse generation in mice, suggesting that feedback through this receptor can occur via a small number of KNDy cells or a yet unidentified cell population.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":"2 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205894","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

MED12 and CDK8/19 modulate androgen receptor activity and enzalutamide response in prostate cancer. MED12 和 CDK8/19 可调节前列腺癌中雄激素受体的活性和恩杂鲁胺的反应。

IF 4.8 3区医学

Endocrinology Pub Date : 2024-09-10 DOI: 10.1210/endocr/bqae114

Chiara Andolfi,Caterina Bartolini,Elisa Morales,Büşra Gündoğdu,Martin Puhr,Juan Guzman,Sven Wach,Helge Taubert,Achim Aigner,Iris E Eder,Florian Handle,Zoran Culig

{"title":"MED12 and CDK8/19 modulate androgen receptor activity and enzalutamide response in prostate cancer.","authors":"Chiara Andolfi,Caterina Bartolini,Elisa Morales,Büşra Gündoğdu,Martin Puhr,Juan Guzman,Sven Wach,Helge Taubert,Achim Aigner,Iris E Eder,Florian Handle,Zoran Culig","doi":"10.1210/endocr/bqae114","DOIUrl":"https://doi.org/10.1210/endocr/bqae114","url":null,"abstract":"Prostate cancer progression is driven by androgen receptor (AR) activity, which is a target for therapeutic approaches. Enzalutamide is an AR inhibitor that prolongs the survival of patients with advanced prostate cancer. However, resistance mechanisms arise and impair its efficacy. One of these mechanisms is the expression of AR-V7, a constitutively active AR splice variant. The Mediator complex is a multi-subunit protein that modulates gene expression on a genome-wide scale. MED12 and cyclin-dependent kinase 8 (CDK8), or its paralog CDK19, are components of the kinase module that regulates the proliferation of prostate cancer cells. In this study, we investigated how MED12 and CDK8/19 influence cancer-driven processes in prostate cancer cell lines, focusing on AR activity and the enzalutamide response. We inhibited MED12 expression and CDK8/19 activity in LNCaP (AR+, enzalutamide-sensitive), 22Rv1 (AR-V7+, enzalutamide-resistant), and PC3 (AR-, enzalutamide-insensitive) cells. Both MED12 and CDK8/19 inhibition reduced cell proliferation in all cell lines, and MED12 inhibition reduced proliferation in the respective 3D spheroids. MED12 knockdown significantly inhibited c-Myc protein expression and signaling pathways. In 22Rv1 cells, it consistently inhibited the AR response, prostate-specific antigen (PSA) secretion, AR target genes, and AR-V7 expression. Combined with enzalutamide, MED12 inhibition additively decreased the AR activity in both LNCaP and 22Rv1 cells. CDK8/19 inhibition significantly decreased PSA secretion in LNCaP and 22Rv1 cells and, when combined with enzalutamide, additively reduced proliferation in 22Rv1 cells. Our study revealed that MED12 and CDK8/19 regulate AR activity and that their inhibition may modulate response to enzalutamide in prostate cancer.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":"10 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205942","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