Endocrinology最新文献_第10页

B2R-D2R Interaction in Prolactinomas and Nonfunctional Adenomas: Impact on Dopamine Resistance. 催乳素瘤和非功能性腺瘤中的 B2R-D2R 相互作用：对多巴胺抗性的影响。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-30 DOI: 10.1210/endocr/bqae144

Alejandra Abeledo-Machado, Josep Argerich, Agustín Yaneff, Noemi Vidal, Claudia García-Roca, Dana Bornancini, Milagros Peña-Zanoni, Mariela M Gironacci, Carina Shayo, Francisco Ciruela, Graciela Díaz-Torga

{"title":"B2R-D2R Interaction in Prolactinomas and Nonfunctional Adenomas: Impact on Dopamine Resistance.","authors":"Alejandra Abeledo-Machado, Josep Argerich, Agustín Yaneff, Noemi Vidal, Claudia García-Roca, Dana Bornancini, Milagros Peña-Zanoni, Mariela M Gironacci, Carina Shayo, Francisco Ciruela, Graciela Díaz-Torga","doi":"10.1210/endocr/bqae144","DOIUrl":"10.1210/endocr/bqae144","url":null,"abstract":"Prolactinomas, the most common pituitary-secreting adenomas, can be effectively treated with dopamine D2 receptor (D2R) agonists. However, a subset of them (∼20%) are resistant to dopamine-based therapies and require extirpation. The molecular mechanisms underlying their escape from dopaminergic regulation are not fully elucidated and may include alterations in D2R signaling. D2R can heteromerize with other G protein-coupled receptors, resulting in modulation of dopaminergic signaling. Because the bradykinin receptor type 2 (B2R) is overexpressed in prolactinomas, we interrogated whether this dopaminergic dysregulation observed in some prolactinomas may depend on a physical and functional interaction between D2R and B2R. The formation of B2R-D2R complexes in cultured cells transiently expressing both receptors was validated using NanoBiT technology. Interestingly, although D2R stimulation did not alter B2R-induced intracellular calcium mobilization, B2R stimulation abolished D2R signaling through modulation of cAMP. The existence of B2R-D2R complexes in pituitary adenomas biopsies was evaluated using an ALPHALisa approach. Importantly, B2R-D2R complexes were detected in human prolactinomas and nonfunctioning pituitary adenomas, but not in mixed (prolactin + growth hormone)-secreting adenomas. These results suggest that overexpression of B2R in resistant prolactinomas may promote the formation of B2R-D2R complexes, with B2R precluding D2R signaling, thus generating resistance to D2R agonists.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564014","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

Prenatal Maternal Stress Suppresses Embryonic Neurogenesis via Elevated Glucocorticoid Levels. 产前母体应激通过升高糖皮质激素水平抑制胚胎神经发生

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-30 DOI: 10.1210/endocr/bqae150

Shujie Xu, Junzhu Shi, Yao Shen, Xianlong Chen, Ghazal Pourbozorg, Guang Wang, Xuesong Yang, Xin Cheng

{"title":"Prenatal Maternal Stress Suppresses Embryonic Neurogenesis via Elevated Glucocorticoid Levels.","authors":"Shujie Xu, Junzhu Shi, Yao Shen, Xianlong Chen, Ghazal Pourbozorg, Guang Wang, Xuesong Yang, Xin Cheng","doi":"10.1210/endocr/bqae150","DOIUrl":"10.1210/endocr/bqae150","url":null,"abstract":"Although it is known that prenatal maternal stress (PNMS) has a negative influence on nervous system development in offspring, there is no conclusive evidence clarifying its impact on early neurogenesis during development. In this study, we established a chick embryo model to investigate how PNMS affects early neurogenesis by mimicking an intrauterine environment with elevated dexamethasone levels. The results showed that dexamethasone-mimicked PNMS significantly suppressed the development of gastrula embryos and increased the risks of neural tube defects and cranial deformity. Using immunofluorescence staining and Western blots to evaluate the expression levels of pHIS3 and PCNA/Sox2, we found that PNMS significantly inhibited the proliferation of neural progenitor cells and that the downregulation of TGF-β signaling pathway might be responsible for the inhibition. Furthermore, immunofluorescence staining and Western blots manifested that PNMS could suppress the differentiation of neural progenitor cells to neuronal lineages, but promote them to transform into neuroglial cells, which might be due to the restriction of expressions of key genes (BMP4, SHH, Wnt3a, Slug, and Msx1) related to neural differentiation. In summary, our data reveal that PNMS dramatically impacts the earliest stages of neural development, thereby greatly increasing the risk of physical and mental health problems in childhood or adulthood.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581785","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

Sex-Based Differences in Thyroid Plasma B Cell Infiltration: Implications for Autoimmune Disease Susceptibility. 甲状腺血浆 B 细胞浸润的性别差异：对自身免疫性疾病易感性的影响

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-30 DOI: 10.1210/endocr/bqae148

Amanda Pereira Vasconcelos, Juan Carlo Santos E Silva, Adriana Simizo, Jonathan Peña Avila, Gabriel Nassar Reich Goldstein, Pedro Henrique Prado de Oliveira, Henry Mogollón García, Carlos Alberto de Carvalho Fraga, Helder I Nakaya

{"title":"Sex-Based Differences in Thyroid Plasma B Cell Infiltration: Implications for Autoimmune Disease Susceptibility.","authors":"Amanda Pereira Vasconcelos, Juan Carlo Santos E Silva, Adriana Simizo, Jonathan Peña Avila, Gabriel Nassar Reich Goldstein, Pedro Henrique Prado de Oliveira, Henry Mogollón García, Carlos Alberto de Carvalho Fraga, Helder I Nakaya","doi":"10.1210/endocr/bqae148","DOIUrl":"10.1210/endocr/bqae148","url":null,"abstract":"Thyroid autoimmune diseases, such as Hashimoto thyroiditis and Graves disease, are significantly more prevalent in women than in men, suggesting underlying biological differences in immune system function and regulation between sexes. Plasma B cells are crucial in autoimmunity due to their role in producing antibodies targeting self-antigens, but their presence in the thyroids of women without clinical autoimmune diseases remains largely unexplored. This study investigates the infiltration of plasma B cells in female thyroids specifically excluding those with any clinical signs of autoimmune diseases. Using bulk RNA-seq analysis, we identified significant sex differences in gene expression profiles, particularly in genes associated with plasma B cells. Single-cell RNA-seq and spatial transcriptomic analyses further revealed that the CXCL13-CXCR5 signaling axis plays a pivotal role in recruiting and organizing plasma B cells within the thyroid tissue. These findings suggest that the inherent presence of plasma B cells in the female thyroid, driven by CXCL13, may contribute to the higher risk of developing autoimmune thyroid diseases in women. Our study provides new insights into the immune landscape of the thyroid and underscores the importance of understanding sex-specific differences in immune cell distribution and function.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564040","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

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

Roles of Growth Hormone-Dependent JAK-STAT5 and Lyn Kinase Signaling in Determining Lifespan and Cancer Incidence. 生长激素依赖性 JAK-STAT5 和 Lyn 激酶信号在决定寿命和癌症发病率中的作用。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-09-26 DOI: 10.1210/endocr/bqae136

Yash Chhabra, Helle Bielefeldt-Ohmann, Tania Louise Brooks, Andrew James Brooks, Michael J Waters

{"title":"Roles of Growth Hormone-Dependent JAK-STAT5 and Lyn Kinase Signaling in Determining Lifespan and Cancer Incidence.","authors":"Yash Chhabra, Helle Bielefeldt-Ohmann, Tania Louise Brooks, Andrew James Brooks, Michael J Waters","doi":"10.1210/endocr/bqae136","DOIUrl":"10.1210/endocr/bqae136","url":null,"abstract":"In rodents, loss of growth hormone (GH) or its receptor is associated with extended lifespan. We aimed to determine the signaling process resulting in this longevity using GH receptor (GHR)-mutant mice with key signaling pathways deleted and correlate this with cancer incidence and expression of genes associated with longevity. GHR uses both canonical janus kinase (JAK)2-signal transducer and activator of transcription (STAT) signaling as well as signaling via the LYN-ERK1/2 pathway. We used C57BL/6 mice with loss of key receptor tyrosines and truncation resulting in 1) loss of most STAT5 response to GH; 2) total inability to generate STAT5 to GH; 3) loss of Box1 to prevent activation of JAK2 but not LYN kinase; or 4) total knockout of the receptor. For each mutant we analyzed lifespan, histopathology to determine likely cause of death, and hepatic gene and protein expression. The extended lifespan is evident in the Box1-mutant males (retains Lyn activation), which have a median lifespan of 1016 days compared to 890 days for the Ghr-/- males. In the females, GhrBox1-/- mice have a median lifespan of 970 days compared to 911 days for the knockout females. Sexually dimorphic GHR-STAT5 is repressive for longevity, since its removal results in a median lifespan of 1003 days in females compared to 734 days for wild-type females. Numerous transcripts related to insulin sensitivity, oxidative stress response, and mitochondrial function are regulated by GHR-STAT5; however, LYN-responsive genes involve DNA repair, cell cycle control, and anti-inflammatory response. There appears to be a yin-yang relationship between JAK2 and LYN that determines lifespan.","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/PMC11500606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388982","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: "Downregulation of CerS4 Instead of CerS2 in Liver Effectively Alleviates Hepatic Insulin Resistance in HFD Male Mice". 更正："下调肝脏中的 CerS4 而非 CerS2 能有效缓解高脂饮食雄性小鼠的肝脏胰岛素抵抗"。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-09-26 DOI: 10.1210/endocr/bqae135

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 : 2024-09-26 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":"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 laymen 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":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-09-26","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

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 : 2024-09-26 DOI: 10.1210/endocr/bqae131

Shiori Mizuma, Tohru Hira

引用次数: 0

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 : 2024-09-26 DOI: 10.1210/endocr/bqae133

Jamie W Joseph

引用次数: 0

Functions and Mechanism of Thyroid Hormone Receptor Action During Amphibian Development. 甲状腺激素受体在两栖动物发育过程中的功能和作用机制

IF 3.8 3区医学

Endocrinology Pub Date : 2024-09-26 DOI: 10.1210/endocr/bqae137

Emeric Louis, Liezhen Fu, Yun-Bo Shi, Laurent M Sachs

{"title":"Functions and Mechanism of Thyroid Hormone Receptor Action During Amphibian Development.","authors":"Emeric Louis, Liezhen Fu, Yun-Bo Shi, Laurent M Sachs","doi":"10.1210/endocr/bqae137","DOIUrl":"10.1210/endocr/bqae137","url":null,"abstract":"Thyroid hormones and their receptors (TRs) play critical roles during vertebrate development. One of the most dramatic developmental processes regulated by thyroid hormones is frog metamorphosis, which mimics the postembryonic (perinatal) period in mammals. Here, we review some of the findings on the developmental functions of thyroid hormones and TRs as well as their associated mechanisms of action obtained from this model system. More than 2 decades ago, a dual function model was proposed for TR in anuran development. During larval development, unliganded receptors recruit corepressors to repress thyroid hormone response genes to prevent premature metamorphic changes. Subsequently, when thyroid hormone levels rise, liganded receptors recruit coactivators to activate thyroid hormone response genes, leading to metamorphic changes. Over the years, molecular and genetic approaches have provided strong support for this model and have shown that it is applicable to mammalian development as well as to understanding the diverse effects of thyroid hormones in normal physiology and diseases caused by thyroid hormone signaling dysfunction.","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/PMC11497603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460915","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