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Estrogen, insulin

Susan M Farabaugh, Bonita T Chan, Xiaojiang Cui, Robert K Dearth, Adrian V Lee
BACKGROUND: ErbB2 Receptor Tyrosine Kinase 2 (ErbB2, HER2/Neu) is amplified in breast cancer and associated with poor prognosis. Growing evidence suggests interplay between ErbB2 and insulin-like growth factor (IGF) signaling. For example, ErbB2 inhibitors can block IGF-induced signaling while, conversely, IGF1R inhibitors can inhibit ErbB2 action. ErbB receptors can bind and phosphorylate insulin receptor substrates (IRS) and this may be critical for ErbB-mediated anti-estrogen resistance in breast cancer...
October 21, 2016: Cell Communication and Signaling: CCS
Marc A Becker, Xiaonan Hou, Piyawan Tienchaianada, Brian B Haines, Sean C Harrington, S John Weroha, Sriram Sathyanarayanan, Paul Haluska
BACKGROUND: Mammalian target of rapamycin (mTOR) represents a key downstream intermediate for a myriad of oncogenic receptor tyrosine kinases. In the case of the insulin-like growth factor (IGF) pathway, the mTOR complex (mTORC1) mediates IGF-1 receptor (IGF-1R)-induced estrogen receptor alpha (ERα) phosphorylation/activation and leads to increased proliferation and growth in breast cancer cells. As a result, the prevalence of mTOR inhibitors combined with hormonal therapy has increased in recent years...
October 20, 2016: BMC Cancer
Tetsuo Mitsui, Maho Ishida, Michi Izawa, Jun Arita
Estrogen binds to nuclear estrogen receptors (ERs) to modulate transcription of target genes in estrogen-responsive cells. However, recent studies have shown that estrogen also binds to cytoplasmic membrane ERs to modulate protein kinase signaling cascades, leading to non-genomic actions. We investigated whether either nuclear or membrane ERs, including G protein-coupled estrogen receptor 1 (Gper1), mediate the inhibitory action of estrogen on insulin-like growth factor-1 (IGF-1)-induced proliferation of pituitary lactotrophs in primary culture...
October 19, 2016: Endocrine Journal
Lola Corzo, Susana Rodríguez, Ramón Alejo, Lucía Fernández-Novoa, Gjumrakch Aliev, Ramón Cacabelos
Menopause is a natural event in women´s lives leading to the cessation of menstruation and the reproductive function due to loss of the ovarian follicular function. Menopause-derived estrogen deprivation and related endocrine factors are linked to some symptoms of middle-aged women, such as hot flashes, aches, joint pain, stiffness, depressed mood, bone degeneration, nutritional dysfunction, or difficulty to maintain body mass. Clinical approaches to these problems often involve hormone replacement therapy (HRT) and other modalities of therapeutic intervention...
October 14, 2016: Current Drug Metabolism
Maike Zimmermann, Aruni P S Arachchige-Don, Michaela S Donaldson, Tommaso Patriarchi, Mary C Horne
Definition of cell cycle control proteins that modify tumor cell resistance to estrogen (E2) signaling antagonists could inform clinical choice for estrogen receptor positive (ER+) breast cancer (BC) therapy. Cyclin G2 (CycG2) is upregulated during cell cycle arrest responses to cellular stresses and growth inhibitory signals and its gene, CCNG2, is directly repressed by E2-bound ER complexes. Our previous studies showed that blockade of HER2, PI3K and mTOR signaling upregulates CycG2 expression in HER2+ BC cells, and that CycG2 overexpression induces cell cycle arrest...
October 18, 2016: Cell Cycle
Su Yon Jung, Wendy E Barrington, Dorothy S Lane, Chu Chen, Rowan Chlebowski, Giselle Corbie-Smith, Lifang Hou, Zuo-Feng Zhang, Min-So Paek, Carolyn J Crandall
OBJECTIVE: Bioavailable insulin-like growth factor-I (IGF-I) interacts with obesity and exogenous estrogen (E) in a racial disparity in obesity-related cancer risk, yet their interconnected pathways are not fully characterized. We investigated whether circulating bioavailable IGF-I acted as a mediator of the racial disparity in obesity-related cancers such as breast and colorectal (CR) cancers and how obesity and E use regulate this relationship. METHODS: A total of 2,425 white and 164 African American (AA) postmenopausal women from the Women's Health Initiative Observational Study were followed from October 1, 1993 through August 29, 2014...
October 3, 2016: Menopause: the Journal of the North American Menopause Society
E Candeias, A I Duarte, I Sebastião, M A Fernandes, A I Plácido, C Carvalho, S Correia, R X Santos, R Seiça, M S Santos, C R Oliveira, P I Moreira
Type 2 diabetes (T2D) is a highly concerning public health problem of the twenty-first century. Currently, it is estimated that T2D affects 422 million people worldwide with a rapidly increasing prevalence. During the past two decades, T2D has been widely shown to have a major impact in the brain. This, together with the cognitive decline and increased risk for dementia upon T2D, may arise from the complex interaction between normal brain aging and central insulin signaling dysfunction. Among the several features shared between T2D and some neurodegenerative disorders (e...
October 11, 2016: Molecular Neurobiology
Hong Lu
The liver is essential for survival due to its critical role in the regulation of metabolic homeostasis. Metabolism of xenobiotics, such as environmental chemicals and drugs by the liver protects us from toxic effects of these xenobiotics, whereas metabolism of cholesterol, bile acids (BAs), lipids, and glucose provide key building blocks and nutrients to promote the growth or maintain the survival of the organism. As a well-established master regulator of liver development and function, hepatocyte nuclear factor 4 alpha (HNF4α) plays a critical role in regulating a large number of key genes essential for the metabolism of xenobiotics, metabolic wastes, and nutrients...
September 2016: Acta Pharmaceutica Sinica. B
Shixia Lin, Wei Ji
The aim of the study was to examine the association between sexual precocity and high-molecular weight (HMW)-adiponectin and investigate the correlation of insulin resistance and estrogen levels in obese children. In total, 60 obese children (30 boys and 30 girls) with sexual precocity were included in group A, 60 obese children (30 boys and 30 girls) without sexual precocity were included in group B, and 60 average weight children (30 boys and 30 girls) were included in group C. The levels of HMW adiponectin, fasting blood glucose, fasting insulin, luteinizing hormone (LH) peak, estradiol and testosterone were measured...
October 2016: Experimental and Therapeutic Medicine
Aihua Wang, Jing Luo, William Moore, Hana Alkhalidy, Ling Wu, Jinhua Zhang, Wei Zhen, Yao Wang, Deborah J Clegg, Bin Xu, Zhiyong Cheng, Ryan P McMillan, Matthew W Hulver, Dongmin Liu
Recent studies showed that GPR30, a seven-transmembrane G-protein-coupled receptor, is a novel estrogen receptor (ER) that mediates some biological events elicited by estrogen in several types of cancer cells. However, its physiological or pathological role in vivo is unclear. Here, we show that GPR30 knockout (GPRKO) female mice were protected from high-fat diet (HFD)-induced obesity, blood glucose intolerance, and insulin resistance. The decreased body weight gain in GPRKO female mice is due to the reduction in body fat mass...
October 4, 2016: Scientific Reports
Susanne U Miedlich, Nima Karamooz, Stephen R Hammes
OBJECTIVE: Aromatase, or CYP19A1, is a type II cytochrome CYP450 enzyme that catalyzes the conversion of C19 androgens to C18 estrogens. Its crucial role in both female and male physiology has been deduced from human and animal studies using aromatase inhibitors, genetically altered mice, and patients with aromatase deficiency. The latter is an extremely rare disorder. Its diagnosis is particularly difficult in males, who go through puberty normally and therefore usually present as adults with elevated testosterone, bone abnormalities (e...
September 29, 2016: Bone
Ida Marie Boisen, Lasse Bøllehuus Hansen, Li Juel Mortensen, Beate Lanske, Anders Juul, Martin Blomberg Jensen
Vitamin D is a versatile signaling molecule with an established role in the regulation of calcium homeostasis and bone health. In recent years the spectrum of vitamin D target organs has expanded and a reproductive role is supported by the presence of the vitamin D receptor (VDR) and the vitamin D metabolizing enzymes in the gonads, reproductive tract, and human spermatozoa. Interestingly, expression levels of VDR and the vitamin D inactivating enzyme CYP24A1 in human spermatozoa serve as positive predictive markers of semen quality and are higher expressed in spermatozoa from normal than infertile men...
September 28, 2016: Journal of Steroid Biochemistry and Molecular Biology
Emily A Southmayd, Mary Jane De Souza
Bone growth, development, and remodeling are modulated by numerous circulating hormones. Throughout the lifespan, the extent to which each of the hormones impacts bone differs. Understanding the independent and combined impact of these hormones on controlling bone remodeling allows for the development of more informed decision making regarding pharmacology, specifically the use of hormonal medication, at all ages. Endocrine control of bone health in women is largely dictated by the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis and the hypothalamic-pituitary-ovarian (HPO) axis...
September 13, 2016: Growth Hormone & IGF Research
Ke He, Hu Qu, Hui Wang, Shun Zhang, Xin-Hong Qian, Wei Li
Metastasis-associated protein 3 (MTA3) is a subunit of the Mi-2/nucleosome remodeling and deacetylase (NuRD) protein complex, with relevant roles in the regulation of cancerous epithelial to mesenchymal transition (ETM) in an estrogen-dependent manner, recently involved in the modulation of different physiological processes. Although these findings connect MTA3 expression with hormonal signaling in various systems, little is known about whether this relationship is conserved in testis where hormonal action is intensive...
September 27, 2016: Endocrinology
Ammy M Santiago, Deborah J Clegg, Vanessa H Routh
OBJECTIVE: 17β-Estradiol (17βE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17βE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase...
September 22, 2016: Physiology & Behavior
Aurèle Besse-Patin, Mélissa Léveillé, Daniel Oropeza, Bich N Nguyen, Annick Prat, Jennifer L Estall
BACKGROUND & AIMS: Inefficient fatty acid oxidation in mitochondria and increased oxidative damage are features of non-alcoholic fatty liver disease (NAFLD). In rodent models and patients with NAFLD, hepatic expression of PPARG coactivator 1 alpha (PPARGC1A or PGC1A) is inversely correlated with liver fat and disease severity. A common polymorphism in this gene (rs8192678, encoding Gly482Ser) has been associated with NAFLD. We investigated whether reduced expression of PGC1A contributes to development of NAFLD using mouse models, primary hepatocytes and human cell lines...
September 19, 2016: Gastroenterology
Hadar Goldvaser, Shulamith Rizel, Daniel Hendler, Victoria Neiman, Daniel Shepshelovich, Tzippy Shochat, Aaron Sulkes, Baruch Brenner, Rinat Yerushalmi
Purpose. To evaluate the associations between metformin, insulin, statins, and levothyroxine and breast cancer characteristics and outcome. Methods. Retrospective chart review of patients treated in our institute for early estrogen receptor (ER) positive, human epidermal growth factor receptor 2 negative breast cancer, whose tumors were sent to Oncotype DX (ODX) analysis. Patients were grouped according to medications usage during the time of breast cancer diagnosis. Each group was compared to the rest of the study population...
2016: International Journal of Endocrinology
Franck Mauvais-Jarvis
The gonads have long been considered endocrine glands, producing sex steroids such as estrogens, androgens, and progesterone (P4) for the sole purpose of sexual differentiation, puberty, and reproduction. Reproduction and energy metabolism are tightly linked, however, and gonadal steroids play an important role in sex-specific aspects of energy metabolism in various physiological conditions. In that respect, gonadal steroids also influence the secretion of insulin in a sex-specific manner. This review presents a perspective on the physiological roles of estrogens, androgens, and P4 via their receptors in pancreatic β cells in the gender-specific tuning of insulin secretion...
September 15, 2016: Trends in Endocrinology and Metabolism: TEM
Jingfang Zou, Liangli Hong, Chaohuan Luo, Zhi Li, Yuzhang Zhu, Tianliang Huang, Yongneng Zhang, Huier Yuan, Yaqiu Hu, Tengfei Wen, Wanling Zhuang, Bozhi Cai, Xin Zhang, Jiexiong Huang, Jidong Cheng
Metformin is an oral biguanide commonly used for the treating type II diabetes and has recently been demonstrated to possess anti-proliferative properties that can be exploited for the prevention and treatment of a variety of cancers. The mechanisms underlying this effect have not been fully elucidated. Our study demonstrated a marked loss of AMP-activated protein kinase (AMPK) phosphorylation and nuclear FOXO1 protein in estrogen-dependent endometrial cancer (EC) tumors compared to normal control endometrium...
September 16, 2016: Cancer Science
Nadja P Maric, Milica J Jovicic, Marina Mihaljevic, Cedo Miljevic
Preclinical Research After the identification of the schizophrenia as an illness over a century ago, treatment of affected individuals included unspecific, mostly very robust methods including deep insulin coma and lobectomy/leucotomy. The first relatively specific treatment of schizophrenia started about 60 years ago with the antipsychotic chlorpromazine. All currently approved antipsychotic drugs block dopamine receptors, indicating that manipulation of dopaminergic function is fundamental to a therapeutic response in psychosis...
September 16, 2016: Drug Development Research
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