Endocrinology最新文献_第3页

Androgens Suppress Corticosteroid Binding Globulin in Male Mice, Affecting the Endocrine Stress Response. 雄性激素抑制雄性小鼠体内的皮质类固醇结合球蛋白，影响内分泌应激反应。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-08-27 DOI: 10.1210/endocr/bqae119

Vera Sommers, Max Gentenaar, Karel David, Nick Narinx, Vanessa Dubois, Jan Kroon, Frank Claessens, Onno C Meijer

{"title":"Androgens Suppress Corticosteroid Binding Globulin in Male Mice, Affecting the Endocrine Stress Response.","authors":"Vera Sommers, Max Gentenaar, Karel David, Nick Narinx, Vanessa Dubois, Jan Kroon, Frank Claessens, Onno C Meijer","doi":"10.1210/endocr/bqae119","DOIUrl":"10.1210/endocr/bqae119","url":null,"abstract":"Biological sex affects the activity of the hypothalamus-pituitary-adrenal (HPA) axis. However, how androgen deprivation affects this axis remains largely unknown. In this study, we investigated the effect of androgen status on different components of the HPA axis in male mice. Two weeks of androgen deprivation did not affect total plasma corticosterone levels but led to increased pituitary ACTH levels. Stress-induced total plasma corticosterone levels were increased, whereas the suppression of corticosterone after dexamethasone treatment under basal conditions was attenuated. Androgen-deprived mice displayed a 2-fold increase in plasma levels of corticosteroid binding globulin (CBG). A similar increase in CBG was observed in global androgen receptor knock-out animals, compared to wild-type littermates. Androgen deprivation was associated with a 6-fold increase in CBG mRNA in the liver and enhanced transcriptional activity at CBG regulatory regions, as evidenced by increased H3K27 acetylation. We propose that the induction of CBG as a consequence of androgen deprivation, together with the unaltered total corticosterone levels, results in lower free corticosterone levels in plasma. This is further supported by mRNA levels of androgen-independent GR target genes in the liver. The reduction in negative feedback on the HPA axis under basal condition would suffice to explain the enhanced stress reactivity after androgen deprivation. Overall, our data demonstrate that, in mice, tonic androgen receptor activation affects CBG levels in conjunction with effects on gene expression and HPA-axis reactivity.","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/PMC11420631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143044","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

Identification of Environmental Compounds That May Trigger Early Female Puberty by Activating Human GnRHR and KISS1R. 识别可能通过激活人类 GnRHR 和 KISS1R 触发女性早期青春期的环境化合物

IF 4.8 3区医学

Endocrinology Pub Date : 2024-08-27 DOI: 10.1210/endocr/bqae103

Shu Yang,Li Zhang,Kamal Khan,Jameson Travers,Ruili Huang,Vukasin M Jovanovic,Rithvik Veeramachaneni,Srilatha Sakamuru,Carlos A Tristan,Erica E Davis,Carleen Klumpp-Thomas,Kristine L Witt,Anton Simeonov,Natalie D Shaw,Menghang Xia

{"title":"Identification of Environmental Compounds That May Trigger Early Female Puberty by Activating Human GnRHR and KISS1R.","authors":"Shu Yang,Li Zhang,Kamal Khan,Jameson Travers,Ruili Huang,Vukasin M Jovanovic,Rithvik Veeramachaneni,Srilatha Sakamuru,Carlos A Tristan,Erica E Davis,Carleen Klumpp-Thomas,Kristine L Witt,Anton Simeonov,Natalie D Shaw,Menghang Xia","doi":"10.1210/endocr/bqae103","DOIUrl":"https://doi.org/10.1210/endocr/bqae103","url":null,"abstract":"There has been an alarming trend toward earlier puberty in girls, suggesting the influence of an environmental factor(s). As the reactivation of the reproductive axis during puberty is thought to be mediated by the hypothalamic neuropeptides kisspeptin and gonadotropin-releasing hormone (GnRH), we asked whether an environmental compound might activate the kisspeptin (KISS1R) or GnRH receptor (GnRHR). We used GnRHR or KISS1R-expressing HEK293 cells to screen the Tox21 10K compound library, a compendium of pharmaceuticals and environmental compounds, for GnRHR and KISS1R activation. Agonists were identified using Ca2+ flux and phosphorylated extracellularly regulated kinase (p-ERK) detection assays. Follow-up studies included measurement of genes known to be upregulated upon receptor activation using relevant murine or human cell lines and molecular docking simulation. Musk ambrette was identified as a KISS1R agonist, and treatment with musk ambrette led to increased expression of Gnrh1 in murine and human hypothalamic cells and expansion of GnRH neuronal area in developing zebrafish larvae. Molecular docking demonstrated that musk ambrette interacts with the His309, Gln122, and Gln123 residues of the KISS1R. A group of cholinergic agonists with structures similar to methacholine was identified as GnRHR agonists. When applied to murine gonadotrope cells, these agonists upregulated Fos, Jun, and/or Egr1. Molecular docking revealed a potential interaction between GnRHR and 5 agonists, with Asn305 constituting the most conservative GnRHR binding site. In summary, using a Tox21 10K compound library screen combined with cellular, molecular, and structural biology techniques, we have identified novel environmental agents that may activate the human KISS1R or GnRHR.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205944","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

ESR1 Fusions Invoke Breast Cancer Subtype-Dependent Enrichment of Ligand-Independent Oncogenic Signatures and Phenotypes. ESR1 融合引发了乳腺癌亚型配体独立致癌特征和表型的富集。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-08-27 DOI: 10.1210/endocr/bqae111

Megan E Yates, Hunter Waltermire, Kanako Mori, Zheqi Li, Yiting Li, Hannah Guzolik, Xiaosong Wang, Tiantong Liu, Jennifer M Atkinson, Jagmohan Hooda, Adrian V Lee, Steffi Oesterreich

{"title":"ESR1 Fusions Invoke Breast Cancer Subtype-Dependent Enrichment of Ligand-Independent Oncogenic Signatures and Phenotypes.","authors":"Megan E Yates, Hunter Waltermire, Kanako Mori, Zheqi Li, Yiting Li, Hannah Guzolik, Xiaosong Wang, Tiantong Liu, Jennifer M Atkinson, Jagmohan Hooda, Adrian V Lee, Steffi Oesterreich","doi":"10.1210/endocr/bqae111","DOIUrl":"10.1210/endocr/bqae111","url":null,"abstract":"Breast cancer is a leading cause of female mortality and despite advancements in personalized therapeutics, metastatic disease largely remains incurable due to drug resistance. The estrogen receptor (ER, ESR1) is expressed in two-thirds of all breast cancer, and under endocrine stress, somatic ESR1 mutations arise in approximately 30% of cases that result in endocrine resistance. We and others reported ESR1 fusions as a mechanism of ER-mediated endocrine resistance. ER fusions, which retain the activation function 1- and DNA-binding domains, harbor ESR1 exons 1 to 6 fused to an in-frame gene partner resulting in loss of the ER ligand-binding domain (LBD). We demonstrate that in a no-special type (invasive ductal carcinoma [IDC]-NST) and an invasive lobular carcinoma (ILC) cell line, ER fusions exhibit robust hyperactivation of canonical ER signaling pathways independent of estradiol or antiendocrine therapies. We employ cell line models stably overexpressing ER fusions with concurrent endogenous ER knockdown to minimize endogenous ER influence. Cell lines exhibited shared transcriptomic enrichment in pathways known to be drivers of metastatic disease, notably MYC signaling. Cells expressing the 3' fusion partners SOX9 and YAP1 consistently demonstrated enhanced growth and cell survival. ILC cells expressing the DAB2 fusion led to enhanced growth, survival, and migration, phenotypes not appreciated in the IDC-NST DAB2 model. Herein, we report that cell line activity is subtype-, fusion-, and assay-specific, suggesting that LBD loss, the fusion partner, and the cellular landscape all influence fusion activities. Therefore, it will be critical to assess fusion frequency in the context of the clinicopathology.","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/PMC11384147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105600","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

Sticky Business: Progesterone Receptors Mediate Cancer Associated Fibroblast and Breast Cancer Cell Interaction. 棘手的问题：孕酮受体介导癌症相关成纤维细胞与乳腺癌细胞的相互作用。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-08-27 DOI: 10.1210/endocr/bqae109

Heather M Brechbuhl, Carol A Sartorius

引用次数: 0

Peripheral Serotonin Controls Dietary Fat Absorption and Chylomicron Secretion via 5-HT4 Receptor in Males. 外周血清素通过 5-HT4 受体控制男性饮食中脂肪的吸收和乳糜微粒的分泌。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-08-27 DOI: 10.1210/endocr/bqae112

Fitore Raka, Simon Hoffman, Asal Nady, Henry Guan, Rianna Zhang, Huaqing Wang, Waliul I Khan, Khosrow Adeli

{"title":"Peripheral Serotonin Controls Dietary Fat Absorption and Chylomicron Secretion via 5-HT4 Receptor in Males.","authors":"Fitore Raka, Simon Hoffman, Asal Nady, Henry Guan, Rianna Zhang, Huaqing Wang, Waliul I Khan, Khosrow Adeli","doi":"10.1210/endocr/bqae112","DOIUrl":"10.1210/endocr/bqae112","url":null,"abstract":"Postprandial dyslipidemia is commonly present in people with type 2 diabetes and obesity and is characterized by overproduction of apolipoprotein B48-containing chylomicron particles from the intestine. Peripheral serotonin is emerging as a regulator of energy homeostasis with profound implications for obesity; however, its role in dietary fat absorption and chylomicron production is unknown. Chylomicron production was assessed in Syrian golden hamsters by administering an olive oil gavage and IP poloxamer to inhibit lipoprotein clearance. Administration of serotonin or selective serotonin reuptake inhibitor, fluoxetine, increased postprandial plasma triglyceride (TG) and TG-rich lipoproteins. Conversely, inhibiting serotonin synthesis pharmacologically by p-chlorophenylalanine (PCPA) led to a reduction in both the size and number of TG-rich lipoprotein particles, resulting in lower plasma TG and apolipoprotein B48 levels. The effects of PCPA occurred independently of gastric emptying and vagal afferent signaling. Inhibiting serotonin synthesis by PCPA led to increased TG within the intestinal lumen and elevated levels of TG and cholesterol in the stool when exposed to a high-fat/high-cholesterol diet. These findings imply compromised fat absorption, as evidenced by reduced lipase activity in the duodenum and lower levels of serum bile acids, which are indicative of intestinal bile acids. During the postprandial state, mRNA levels for serotonin receptors (5-HTRs) were upregulated in the proximal intestine. Administration of cisapride, a 5-HT4 receptor agonist, alleviated reductions in postprandial lipemia caused by serotonin synthesis inhibition, indicating that serotonin controls dietary fat absorption and chylomicron secretion via 5-HT4 receptor.","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/PMC11417612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153402","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

Stanniocalcin Protein Expression in Female Reproductive Organs: Literature Review and Public Cancer Database Analysis. 女性生殖器官中的斯坦尼钙蛋白表达：文献综述和公共癌症数据库分析。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-08-27 DOI: 10.1210/endocr/bqae110

Masuma Khatun, Vijayachitra Modhukur, Terhi T Piltonen, Juha S Tapanainen, Andres Salumets

{"title":"Stanniocalcin Protein Expression in Female Reproductive Organs: Literature Review and Public Cancer Database Analysis.","authors":"Masuma Khatun, Vijayachitra Modhukur, Terhi T Piltonen, Juha S Tapanainen, Andres Salumets","doi":"10.1210/endocr/bqae110","DOIUrl":"10.1210/endocr/bqae110","url":null,"abstract":"Stanniocalcin (STC) 1 and 2 serve as antihyperglycemic polypeptide hormones with critical roles in regulating calcium and phosphate homeostasis. They additionally function as paracrine and/or autocrine factors involved in numerous physiological processes, including female reproduction. STC1 and STC2 contribute to the pathophysiology of several diseases, including female infertility- and pregnancy-associated conditions, and even tumorigenesis of reproductive organs. This comprehensive review highlights the dynamic expression patterns and potential dysregulation of STC1 and STC2, restricted to female fertility, and infertility- and pregnancy-associated diseases and conditions, such as endometriosis, polycystic ovary syndrome (PCOS), abnormal uterine bleeding, uterine polyps, and pregnancy complications, like impaired decidualization, preeclampsia, and preterm labor. Furthermore, the review elucidates the role of dysregulated STC in the progression of cancers of the reproductive system, including endometrial, cervical, and ovarian cancers. Additionally, the review evaluates the expression patterns and prognostic significance of STC in gynecological cancers by utilizing existing public datasets from The Cancer Genome Atlas to help decipher the multifaceted roles of these pleiotropic hormones in disease progression. Understanding the intricate mechanisms by which STC proteins influence all these reviewed conditions could lead to the development of targeted diagnostic and therapeutic strategies in the context of female reproductive health and oncology.","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/PMC11398916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072305","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 Inhibition of Reproductive Neuroendocrine Function in Females and Transgender Males. 雄性激素对女性和变性男性生殖神经内分泌功能的抑制。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-08-27 DOI: 10.1210/endocr/bqae113

Alexander S Kauffman

{"title":"Androgen Inhibition of Reproductive Neuroendocrine Function in Females and Transgender Males.","authors":"Alexander S Kauffman","doi":"10.1210/endocr/bqae113","DOIUrl":"10.1210/endocr/bqae113","url":null,"abstract":"Ovarian function is controlled by pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), which in turn are governed by gonadotropin releasing hormone (GnRH) secreted from the brain. A fundamental principle of reproductive axis regulation is negative feedback signaling by gonadal sex steroids back to the brain to fine-tune GnRH and gonadotropin secretion. Endogenous negative feedback effects can be mimicked by exogenous steroid treatments, including androgens, in both sexes. Indeed, a growing number of clinical and animal studies indicate that high levels of exogenous androgens, in the typically male physiological range, can inhibit LH secretion in females, as occurs in males. However, the mechanisms by which male-level androgens inhibit GnRH and LH secretion still remain poorly understood, and this knowledge gap is particularly pronounced in transgender men (individuals designated female at birth but identifying as male). Indeed, many transgender men take long-term gender-affirming hormone therapy that mimics male-level testosterone levels. The impact of such gender-affirming testosterone on the reproductive axis, both at the ovarian and neuroendocrine level, is a long-understudied area that still requires further investigation. Importantly, the few concepts of androgen actions in females mostly come from studies of polycystic ovary syndrome, which does not recapitulate a similar androgen milieu or a pathophysiology of inhibited LH secretion as occurs in testosterone-treated transgender men. This review summarizes clinical evidence indicating that exogenous androgens can impair neuroendocrine reproductive function in both female individuals and transgender men and highlights emerging experimental data supporting this in recently developed transgender rodent models.","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/PMC11393496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105599","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

The Elusive Search for the Ideal Pharmacological Treatment for Cushing Disease. 寻找理想的库欣病药物治疗方法。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-08-27 DOI: 10.1210/endocr/bqae108

Moisés Mercado

引用次数: 0

Therapeutic Potential of Blocking Nephrin Phosphorylation to Improve Pancreatic β-cell Function. 阻断肾素磷酸化改善胰岛β细胞功能的治疗潜力

IF 3.8 3区医学

Endocrinology Pub Date : 2024-08-27 DOI: 10.1210/endocr/bqae104

Jamie W Joseph

引用次数: 0

Thyroid Hormone Receptors as Tumor Suppressors in Cancer. 甲状腺激素受体是癌症中的肿瘤抑制因子

IF 3.8 3区医学

Endocrinology Pub Date : 2024-08-27 DOI: 10.1210/endocr/bqae115

Xuguang Zhu, Sheue-Yann Cheng

{"title":"Thyroid Hormone Receptors as Tumor Suppressors in Cancer.","authors":"Xuguang Zhu, Sheue-Yann Cheng","doi":"10.1210/endocr/bqae115","DOIUrl":"10.1210/endocr/bqae115","url":null,"abstract":"Accumulated research has revealed the multifaceted roles of thyroid hormone receptors (TRs) as potent tumor suppressors across various cancer types. This review explores the intricate mechanisms underlying TR-mediated tumor suppression, drawing insights from preclinical mouse models and cancer biology. This review examines the tumor-suppressive functions of TRs, particularly TRβ, in various cancers using preclinical models, revealing their ability to inhibit tumor initiation, progression, and metastasis. Molecular mechanisms underlying TR-mediated tumor suppression are discussed, including interactions with oncogenic signaling pathways like PI3K-AKT, JAK-STAT, and transforming growth factor β. Additionally, this paper examines TRs' effect on cancer stem cell activity and differentiation, showcasing their modulation of key cellular processes associated with tumor progression and therapeutic resistance. Insights from preclinical studies underscore the therapeutic potential of targeting TRs to impede cancer stemness and promote cancer cell differentiation, paving the way for precision medicine in cancer treatment and emphasizing the potential of TR-targeted therapies as promising approaches for treating cancers and improving patient outcomes.","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/PMC11406550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125175","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