Endocrinology最新文献

Do ketone supplements regulate islet hormone secretion? 酮补充剂能调节胰岛激素分泌吗？

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-04 DOI: 10.1210/endocr/bqae133

Jamie W Joseph

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 : 2024-10-04 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":"https://doi.org/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 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 DS1 enhancer is kidney-specific and responsible for PTH and FGF23 actions, and the DS2 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. Here 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 pCREB 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":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The LEAP2 response to cancer-related anorexia-cachexia syndrome in male mice and patients. LEAP2 对雄性小鼠和患者癌症相关厌食-痛风综合征的反应

IF 3.8 3区医学

Endocrinology Pub Date : 2024-09-27 DOI: 10.1210/endocr/bqae132

Salil Varshney, Kripa Shankar, Haiming L Kerr, Lindsey J Anderson, Deepali Gupta, Nathan P Metzger, Omprakash Singh, Sean B Ogden, Subhojit Paul, Francisco Piñon, Sherri Osborne-Lawrence, Corine P Richard, Connor Lawrence, Bharath K Mani, Jose M Garcia, Jeffrey M Zigman

{"title":"The LEAP2 response to cancer-related anorexia-cachexia syndrome in male mice and patients.","authors":"Salil Varshney, Kripa Shankar, Haiming L Kerr, Lindsey J Anderson, Deepali Gupta, Nathan P Metzger, Omprakash Singh, Sean B Ogden, Subhojit Paul, Francisco Piñon, Sherri Osborne-Lawrence, Corine P Richard, Connor Lawrence, Bharath K Mani, Jose M Garcia, Jeffrey M Zigman","doi":"10.1210/endocr/bqae132","DOIUrl":"https://doi.org/10.1210/endocr/bqae132","url":null,"abstract":"The hormone ghrelin serves a protective role in cancer-related anorexia-cachexia syndrome (CACS) - a condition in which plasma levels of ghrelin rise, its administration lessens CACS severity, and experimentally-reduced signaling by its receptor (GHSR) worsens fat loss and anorexia and accelerates death. Yet, actions for the related hormone liver-expressed antimicrobial peptide-2 (LEAP2), which is an endogenous GHSR antagonist, are unexplored in CACS. Here, we found that plasma LEAP2 and LEAP2/ghrelin ratio were lower in Lewis Lung Carcinoma (LLC) and RM-9 prostate cancer CACS mouse models. Ghrelin deletion exaggerated losses of tumor-free body weight and fat mass, reduced food intake, reduced soleus muscle weight, and/or lowered grip strength in LLC or RM-9 tumor-bearing mice. LEAP2 deletion lessened reductions in tumor-free body weight and fat mass and increased food intake in LLC or RM-9 tumor-bearing mice. In a 55-subject cohort of patients with CACS or weight-stable cancer, the plasma LEAP2/total ghrelin ratio was negatively correlated with 6-month weight change preceding blood collection. These data demonstrate that ghrelin deletion exacerbates CACS in the LLC and RM-9 tumor-bearing mouse models while contrastingly, LEAP2 deletion reduces measures of CACS in these tumor-bearing mouse models. Further, they suggest that lower plasma LEAP2/ghrelin ratio protects against worsened CACS.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343983","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

Targeting intestinal neprilysin to ameliorate glucose homeostasis through insulinotropic effect. 靶向肠肾素，通过促胰岛素作用改善葡萄糖稳态。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-09-27 DOI: 10.1210/endocr/bqae131

Shiori Mizuma, Tohru Hira

引用次数: 0

27-Hydroxycholesterol Enhances Secretion of Extracellular Vesicles by ROS-Induced Dysregulation of Lysosomes. 27-羟基胆固醇可通过 ROS 诱导的溶酶体失调促进细胞外囊泡的分泌

IF 3.8 3区医学

Endocrinology Pub Date : 2024-09-26 DOI: 10.1210/endocr/bqae127

Anasuya Das Gupta, Jaena Park, Janet E Sorrells, Hannah Kim, Natalia Krawczynska, Dhanya Pradeep, Yu Wang, Hashni Epa Vidana Gamage, Adam T Nelczyk, Stephen A Boppart, Marni D Boppart, Erik R Nelson

{"title":"27-Hydroxycholesterol Enhances Secretion of Extracellular Vesicles by ROS-Induced Dysregulation of Lysosomes.","authors":"Anasuya Das Gupta, Jaena Park, Janet E Sorrells, Hannah Kim, Natalia Krawczynska, Dhanya Pradeep, Yu Wang, Hashni Epa Vidana Gamage, Adam T Nelczyk, Stephen A Boppart, Marni D Boppart, Erik R Nelson","doi":"10.1210/endocr/bqae127","DOIUrl":"10.1210/endocr/bqae127","url":null,"abstract":"Extracellular vesicles (EVs) serve as crucial mediators of cell-to-cell communication in normal physiology as well as in diseased states; they have been largely studied in regard to their role in cancer progression. However, the mechanisms by which their biogenesis and secretion are regulated by metabolic or endocrine factors remain unknown. Here, we delineate a mechanism by which EV secretion is regulated by a cholesterol metabolite, 27-hydroxycholesterol (27HC), where treatment of myeloid immune cells (RAW 264.7 and J774A.1) with 27HC impairs lysosomal homeostasis, leading to shunting of multivesicular bodies (MVBs) away from lysosomal degradation, toward secretion as EVs. This altered lysosomal function is likely caused by mitochondrial dysfunction and subsequent increase in reactive oxygen species (ROS). Interestingly, cotreatment with a mitochondria-targeted antioxidant rescued the lysosomal impairment and attenuated the 27HC-mediated increase in EV secretion. Overall, our findings establish how a cholesterol metabolite regulates EV secretion and paves the way for the development of strategies to regulate cancer progression by controlling EV secretion.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282310","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 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

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 : 2024-09-23 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":"https://doi.org/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 life span, growth, and differentiation are tightly regulated by survival and cell death signals through luteotrophic and luteolytic factors, including the 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 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 factors 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, 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":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GLP-1, GIP, and Glucagon Agonists for Obesity Treatment: A Hunger Perspective. 治疗肥胖症的 GLP-1、GIP 和胰高血糖素激动剂：饥饿视角。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-09-20 DOI: 10.1210/endocr/bqae128

Mateus D'Ávila, Samantha Hall, Tamas L Horvath

{"title":"GLP-1, GIP, and Glucagon Agonists for Obesity Treatment: A Hunger Perspective.","authors":"Mateus D'Ávila, Samantha Hall, Tamas L Horvath","doi":"10.1210/endocr/bqae128","DOIUrl":"https://doi.org/10.1210/endocr/bqae128","url":null,"abstract":"For centuries, increasingly sophisticated methods and approaches have been brought to bear to promote weight loss. Second, only to the Holy Grail of research on aging, the idea of finding a single and simple way to lose weight has long preoccupied the minds of layman. and scientists alike. The effects of obesity are far-reaching and not to be minimized; the need for more effective treatments is obvious. Is there a single silver bullet that addresses this issue without effort on the part of the individual? The answer to this question has been one of the most elusive and sought-after in modern history. Now and then, a miraculous discovery propagates the illusion that a simple solution is possible. Now, there are designer drugs that seem to accomplish the task: we can lose weight without effort using mono-, dual-, and triple agonists of receptors for glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon. There are, however, fundamental biological principles that raise intriguing questions about these therapies beyond the currently reported side effects. This perspective reflects upon these issues from the angle of complex goal-oriented behaviors, and systemic and cellular metabolism associated with satiety and hunger.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282311","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

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 : 2024-09-16 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":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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":null,"pages":null},"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