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Estrogen, insulin

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https://www.readbyqxmd.com/read/28735214/indazole-based-ligands-for-estrogen-related-receptor-%C3%AE-as-potential-anti-diabetic-agents
#1
Raymond J Patch, Hui Huang, Sharmila Patel, Wing Cheung, Guozhang Xu, Bao-Ping Zhao, Derek A Beauchamp, Dionisios Rentzeperis, John G Geisler, Hossein B Askari, Jianying Liu, Jyotsna Kasturi, Meghan Towers, Micheal D Gaul, Mark R Player
Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that has been functionally implicated in the regulation of energy homeostasis. Herein is described the development of indazole-based N-alkylthiazolidenediones, which function in biochemical assays as selective inverse agonists against this receptor. Series optimization provided several potent analogues that inhibited the recruitment of a co-activator peptide fragment in vitro (IC50s < 50 nM) and reduced fasted circulating insulin and triglyceride levels in a sub-chronic pre-diabetic rat model when administered orally (10 mg/kg)...
July 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28729437/estradiol-induced-regulation-of-glut4-in-3t3-l1-cells-involvement-of-esr1-and-akt-activation
#2
Raquel Campello, Luciana Fátima, João Barreto-Andrade, Thais Fg Lucas, Rosana Cristina Tieko Mori, Catarina Segreti Porto, Ubiratan Fabres Machado
Impaired insulin-stimulated glucose uptake involves reduced expression of the GLUT4 (solute carrier family 2 facilitated glucose transporter member 4, SLC2A4 gene). 17β-estradiol (E2) modulates SLC2A4/GLUT4 expression, but the involved mechanisms are unclear. Although E2 exerts its biological effects by binding to estrogen receptors 1/2 (ESR1/2), which are nuclear transcriptional factors; extranuclear effects have also been proposed. We hypothesize that E2 regulates GLUT4 through a mechanism related to extranuclear ESR1...
July 20, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28713971/systematic-analysis-of-lncrnas-mirnas-and-mrnas-for-the-identification-of-biomarkers-for-osteoporosis-in-the-mandible-of-ovariectomized-mice
#3
Lingyu Hao, Jiayao Fu, Yawen Tian, Junhua Wu
Osteoporosis is a complex and multifactorial disease caused by an imbalance between bone formation and resorption. Post‑menopausal women with endogenous estrogen deficiency suffer from systemic bone loss and osteoporosis, and are at high risk of this affecting the jaw bones. MicroRNAs (miRNAs or miRs) have been implicated in the mechanisms of metabolic bone diseases and are expressed at differential levels in alveolar bone following ovariectomy. In the present study, we systematically analyzed the expression profiles of miRNAs, mRNAs and long non‑coding RNA (lncRNAs) in the mandible of ovariectomized (OVX) mice...
July 10, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28709873/deregulation-of-wnt2-fzd3-%C3%AE-catenin-pathway-compromises-the-estrogen-synthesis-in-cumulus-cells-from-patients-with-polycystic-ovary-syndrome
#4
Gu-Yuan Qiao, Bing-Wei Dong, Chao-Juan Zhu, Chang-You Yan, Bi-Liang Chen
Mechanistic insight into estrogen deficiency by polycystic ovary syndrome (PCOS) remains a longstanding challenge in reproductive medicine. Recent advance suggest that Wingless-type MMTV integration site family members (WNTs), in concert with its Frizzled (FZD) receptors, regulate normal folliculogenesis, luteogenesis and ovarian steroidogenesis. However, no studies have so far investigated any causality between WNT-FZDs interactions and disrupted estrogen synthesis under certain pathological conditions. Here, we show that (i) FZD3 expression was significantly up-regulated in the cumulus cells (CCs) from PCOS patients...
July 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28708856/diabetes-use-of-metformin-and-the-risk-of-meningioma
#5
Corinna Seliger, Christoph R Meier, Claudia Becker, Susan S Jick, Martin Proescholdt, Ulrich Bogdahn, Peter Hau, Michael F Leitzmann
BACKGROUND: Metformin is a commonly used oral antidiabetic agent that has been associated with decreased cancer risk. However, data regarding the association between metformin use and the risk of meningioma are unavailable. METHODS: We conducted a matched case-control analysis using data from the U.K.-based Clinical Practice Research Datalink (CPRD) to analyse diabetes status, duration of diabetes, glycemic control, and use of metformin, sulfonylureas, and insulin in relation to the risk of meningioma...
2017: PloS One
https://www.readbyqxmd.com/read/28708244/mir-199a-3p-is-involved-in-estrogen-mediated-autophagy-through-the-igf-1-mtor-pathway-in-osteocyte-like-mlo-y4-cells
#6
Jiayao Fu, Lingyu Hao, Yawen Tian, Yang Liu, Yijing Gu, Junhua Wu
To date, evidence indicates that estrogen partially modulates cellular processes through microRNAs. Autophagy is a catabolic process that is regulated by multiple factors and is associated with skeletal diseases. However, whether estrogen regulates osteocyte autophagy via microRNAs is largely unknown. In this study, we observed the up-regulation of microRNA-199a-3p, a post-transcriptional regulatory factor, in osteocytic areas in ovariectomized (OVX) mice. The mature forms of miR-199a-3p and pri-miR-199a were produced in response to estrogen signaling in osteocyte-like MLO-Y4 cells...
July 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28684382/a-regulatory-role-of-androgen-in-ovarian-steroidogenesis-by-rat-granulosa-cells
#7
Toru Hasegawa, Yasuhiko Kamada, Takeshi Hosoya, Shiho Fujita, Yuki Nishiyama, Nahoko Iwata, Yuji Hiramatsu, Fumio Otsuka
Excess androgen and insulin-like growth factor (IGF)-I in the ovarian follicle has been suggested to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). Here we investigated the impact of androgen and IGF-I on the regulatory mechanism of ovarian steroidogenesis using rat primary granulosa cells. It was revealed that androgen treatment with dihydrotestosterone (DHT) amplified progesterone synthesis in the presence of FSH and IGF-I, whereas it had no significant effect on estrogen synthesis by rat granulosa cells...
July 3, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28681171/a-randomized-phase-ii-trial-of-ridaforolimus-dalotuzumab-and-exemestane-compared-with-ridaforolimus-and-exemestane-in-patients-with-advanced-breast-cancer
#8
Hope S Rugo, Olivier Trédan, Jungsil Ro, Serafin M Morales, Mario Campone, Antonino Musolino, Noémia Afonso, Marta Ferreira, Kyong Hwa Park, Javier Cortes, Antoinette R Tan, Joanne L Blum, Lamar Eaton, Christine K Gause, Zhen Wang, Ellie Im, David J Mauro, Mary Beth Jones, Andrew Denker, José Baselga
PURPOSE: To evaluate whether adding humanized monoclonal insulin growth factor-1 receptor (IGF-1R) antibody (dalotuzumab) to mammalian target of rapamycin (mTOR) inhibitor (ridaforolimus) plus aromatase inhibitor (exemestane) improves outcomes in patients with estrogen receptor (ER)-positive advanced/metastatic breast cancer. METHODS: This randomized, open-label, phase II trial enrolled 80 postmenopausal women with high-proliferation (Ki67 index staining ≥15%), ER-positive breast cancer that progressed after a non-steroidal aromatase inhibitor (NCT01605396)...
July 5, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28658166/a-cross-sectional-study-on-the-associations-of-insulin-resistance-with-sex-hormone-abnormal-lipid-metabolism-in-t2dm-and-igt-patients
#9
Xiaoxia Wang, Tongzhang Xian, Xiaofan Jia, Lina Zhang, Li Liu, Fuli Man, Xianbo Zhang, Jie Zhang, Qi Pan, Lixin Guo
Type 2 diabetes mellitus (T2DM) is a long-term metabolic disorder. It is characterized by hyperglycemia, insulin resistance (IR), and relative impairment in insulin secretion. IR plays a major role in the pathogenesis of T2DM. Many previous studies have investigated the relationship between estrogen, androgen, and obesity, but few focused on the relationship between sex hormones, abnormal lipid metabolism, and IR. The goal for the present study was to identify the association of IR with sex hormone, abnormal lipid metabolism in type 2 diabetes, and impaired glucose tolerance (IGT) patients...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28655716/increased-adipose-tissue-aromatase-activity-improves-insulin-sensitivity-and-reduces-adipose-tissue-inflammation-in-male-mice
#10
Claes Ohlsson, Ann Hammarstedt, Liesbeth Vandenput, Niina Saarinen, Henrik Ryberg, Sara Windahl, Helen H Farman, John-Olov Janson, Sofia Movérare-Skrtic, Ulf Smith, Fu-Ping Zhang, Matti Poutanen, Shahram Hedjazifar, Klara Sjogren
Females are in general more insulin sensitive than males. To investigate if this is a direct effect of sex-steroids (SS) in white adipose tissue (WAT), we developed a male mouse model over expressing the aromatase enzyme, converting testosterone (T) to estradiol (E2), specifically in WAT (Ap2-arom mice). Adipose tissue E2 levels were increased while circulating SS levels were unaffected in male Ap2-arom mice. Importantly, male Ap2-arom mice were more insulin sensitive compared with WT mice and exhibited increased serum adiponectin levels and upregulated expression of Glut4 and Irs1 in WAT...
June 27, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28645613/regulation-of-testicular-steroidogenesis-by-foxa3-via-transcriptional-modulation-of-er%C3%AE-signaling-in-type-2-diabetes-mellitus-t2dm
#11
Yong Zhao, Hong-Xin Li, Ke Wang, Bin-Yuan Yan, Wei Li
Although both insulin and estrogen receptor α (ERα) are known to exert inhibitory effects on testicular steroidogenesis, it remains unknown whether these pathways regulate testosterone (T) production under certain pathological conditions [e.g., type 2 diabetes mellitus (T2DM)] in a coordinated manner. Here, we found that the expression of forkhead box protein A3 (Foxa3), an essential transcriptional regulator engaged in adipogenesis and energy metabolism, was significantly down-regulated in the Leydig cells (LCs) from T-deficient T2DM mice...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28621254/use-of-microcomputed-tomography-to-measure-the-relaxin-induced-expansion-of-intrapubic-ligaments-in-mice
#12
Heather A Zimmerman, Richard P Kennan, Chunlian Zhang, Kashmira Shah, Douglas G Johns, Joseph J Lynch, Maya Dajee
Relaxin is a 6-kDa peptide in the insulin superfamily of hormones. In addition to its effects on reproductive and musculoskeletal ligaments, relaxin has demonstrated beneficial effects on cardiac, renal, and vascular systems in preclinical models. The mouse intrapubic ligament ex vivo bioassay is the current standard for measuring in vivo relaxin bioactivity. However, this bioassay necessitates euthanasia and dissection of large cohorts to measure the intrapubic ligament at specified time points. We hypothesized that μCT imaging could be used to reduce the number of animals necessary for the intrapubic ligament bioassay by enabling a single animal to be followed longitudinally throughout the study rather than euthanizing different cohorts at established time points...
June 15, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28586424/role-of-er%C3%AE-in-mediating-female-uterine-transcriptional-responses-to-igf1
#13
Sylvia C Hewitt, Wipawee Winuthayanon, Sydney L Lierz, Katherine J Hamilton, Lauren J Donoghue, J Tyler Ramsey, Sara A Grimm, Yukitomo Arao, Kenneth S Korach
Estrogen (E2) signaling through its nuclear receptor, estrogen receptor α (ERα) increases insulin-like growth factor 1 (IGF1) in the rodent uterus, which then initiates further signals via the IGF1 receptor (IGF1R). Directly administering IGF1 results in similar biological and transcriptional uterine responses. Our studies using global ERα-null mice demonstrated a loss of uterine biological responses of the uterus to E2 or IGF1 treatment, while maintaining transcriptional responses to IGF1. To address this discrepancy in the need for uterine ERα in mediating the IGF1 transcriptional vs...
June 6, 2017: Endocrinology
https://www.readbyqxmd.com/read/28585217/obesity-associated-breast-cancer-analysis-of-risk-factors
#14
Atilla Engin
Several studies show that a significantly stronger association is obvious between increased body mass index (BMI) and higher breast cancer incidence. Furthermore, obese women are at higher risk of all-cause and breast cancer specific mortality when compared to non-obese women with breast cancer. In this context, increased levels of estrogens due to excessive aromatization activity of the adipose tissue, overexpression of pro-inflammatory cytokines, insulin resistance, hyperactivation of insulin-like growth factors (IGFs) pathways, adipocyte-derived adipokines, hypercholesterolemia and excessive oxidative stress contribute to the development of breast cancer in obese women...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28575556/-endocrinology-of-cancer-and-age-early-and-late-stages-of-ontogenesis
#15
L M Berstein
Processes important for hormone-mediated carcinogenesis are present on different, even very early, ontogenesis stages. Early shifts in hormone-metabolic status often display opposite correlations with the risk of most common age-associated non-communicable pathologies (namely, hormone-dependent cancers and cardiovascular diseases). Additional known contradiction is the raise of reproductive system tumors incidence in the age associated with lower production of mitogenic hormones. Consequently, one should take into account production of steroids in target tissues themselves, recognize the importance of progenotoxic effect, which, apart from mitogenic function, is characteristic for estrogens and their derivatives, as well as the role of endocrine-genotoxic switchings forming so called basic triad, which is born under the influence of age-associated endocrine shifts and environmental factors...
2017: Advances in Gerontology, Uspekhi Gerontologii
https://www.readbyqxmd.com/read/28559116/uterine-er%C3%AE-epigenetic-modifications-are-induced-by-the-endocrine-disruptor-endosulfan-in-female-rats-with-impaired-fertility
#16
María M Milesi, Jorgelina Varayoud, Jorge G Ramos, Enrique H Luque
High ERα activity may disrupt the window of uterine receptivity, causing defective implantation. We investigated whether implantation failures prompted by endosulfan are associated with aberrant ERα uterine expression and DNA methylation status during the pre-implantation period. ERα-dependent target genes that play a crucial role in the uterine receptivity for embryo attachment and implantation were also investigated. Newborn female rats received corn oil (vehicle, Control), 6 μg/kg/d of endosulfan (Endo6) or 600 μg/kg/d of endosulfan (Endo600) on postnatal days (PND) 1, 3, 5, and 7...
May 27, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28551627/the-cooh-terminus-of-the-igf-1ec-isoform-enhances-the-proliferation-and-migration-of-human-mcf-7-breast-cancer-cells
#17
Panagiotis F Christopoulos, Efstathia Papageorgiou, Constantina Petraki, Michael Koutsilieris
BACKGROUND/AIM: The insulin-like growth factor-1 (IGF-1) signaling is well implicated in cancer biology, however the potential roles of the distinct IGF-1 isoforms in human malignancies are largely unknown. Recently, the carboxyl-terminal of the IGF-1Ec variant (hEc; 24aa) has been associated with osteosarcoma and prostate cancer. Herein, we investigated the potential role of hEc in breast cancer. MATERIALS AND METHODS: Synthetic hEc peptide was administrated to MCF-7 and MDA-MB-231 breast cancer cells...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28533226/igf1r-protein-expression-is-not-associated-with-differential-benefit-to-concurrent-trastuzumab-in-early-stage-her2-breast-cancer-from-the-north-central-cancer-treatment-group-alliance-adjuvant-trastuzumab-trial-n9831
#18
Monica M Reinholz, Beiyun Chen, Amylou C Dueck, Kathleen Tenner, Karla Ballman, Darren Riehle, Robert B Jenkins, Xochiquetzal J Geiger, Ann E McCullough, Edith A Perez
Background: Preclinical evidence indicates that increased insulin-like growth factor receptor-1 (IGF1R) signaling interferes with the action of trastuzumab suggesting a possible mechanism of trastuzumab resistance. Thus, we evaluated IGF1R prevalence, relationship with demographic data, and association with disease-free survival (DFS) of patients randomized to chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C) in the prospective phase III HER2(+) adjuvant N9831 trial...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28521865/exaggerated-glucagon-responses-to-hypoglycemia-in-women-with-polycystic-ovary-syndrome
#19
Susan Sam, Priyathama Vellanki, Sudha K Yalamanchi, Richard N Bergman, Andrea Dunaif
CONTEXT: Premenopausal women have blunted counter-regulatory hormone responses (CRR) to hypoglycemia compared to men. Postmenopausal women have CRR similar to men; the premenopausal pattern can be restored by estrogen. However, glucagon and pancreatic polypeptide (PP) responses remain lower in postmenopausal women than in men. Since hyperandrogenemia contributes to the metabolic phenotype of polycystic ovary syndrome (PCOS), we hypothesize that CRR to hypoglycemia especially of glucagon and PP is exaggerated in premenopausal women with PCOS compared to premenopausal control women...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28515690/brain-renin-angiotensin-system-and-microglial-polarization-implications-for-aging-and-neurodegeneration
#20
REVIEW
Jose L Labandeira-Garcia, Ana I Rodríguez-Perez, Pablo Garrido-Gil, Jannette Rodriguez-Pallares, Jose L Lanciego, Maria J Guerra
Microglia can transform into proinflammatory/classically activated (M1) or anti-inflammatory/alternatively activated (M2) phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS) on microglial polarization are less known...
2017: Frontiers in Aging Neuroscience
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