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Endometrium insulin estrogen

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
M Sequeira, S J Pain, V de Brun, A Meikle, P R Kenyon, H T Blair
The objective of this study was to investigate the gene expression of progesterone and estrogen receptor α (PR, ERα), insulin-like growth factor (IGF) 1, IGF-2, their receptor (IGFR1), IGF-binding proteins (BP) 1 to 6, insulin receptor, adiponectin receptors (AdipoR1/2), cyclooxygenase 2 (PTGS2), mucin 1 and to localize PR, ERα, IGF-1, IGFR1, PTGS2, and proliferating cellular nuclear antigen (PCNA) in the endometrium of pregnant (Day 19) Suffolk and Cheviot ewes carrying Suffolk and Cheviot embryos transferred within and reciprocally between breeds...
October 1, 2016: Theriogenology
Terhi T Piltonen
Women with polycystic ovarian syndrome (PCOS) present with several endometrial abnormalities possibly explaining some of the adverse endometrium-related outcomes in these women. PCOS and an increased miscarriage rate have been suggested to coincide, but the results are conflicting. Recent studies have also shown increased risks of pregnancy-induced hypertension, preeclampsia, and premature delivery that may be related to altered decidualization/placentation in affected women. In the long run, PCOS per se is associated with the occurrence of endometrial cancer (EC), with obesity aggravating the risk...
April 1, 2016: Best Practice & Research. Clinical Obstetrics & Gynaecology
Melissa A Merritt, Howard D Strickler, Mark H Einstein, Hannah P Yang, Mark E Sherman, Nicolas Wentzensen, Jurriaan Brouwer-Visser, Maria Jose Cossio, Kathleen D Whitney, Herbert Yu, Marc J Gunter, Gloria S Huang
PURPOSE: Experimental and observational data link insulin, insulin-like growth factor (IGF), and estrogens to endometrial tumorigenesis. However, there are limited data regarding insulin/IGF and sex hormone axes protein and gene expression in normal endometrial tissues, and very few studies have examined the impact of endometrial cancer risk factors on endometrial tissue biology. METHODS: We evaluated endometrial tissues from 77 premenopausal and 30 postmenopausal women who underwent hysterectomy for benign indications and had provided epidemiological data...
June 2016: Cancer Causes & Control: CCC
Clare A Flannery, Farrah L Saleh, Gina H Choe, Daryl J Selen, Pinar H Kodaman, Harvey J Kliman, Teresa L Wood, Hugh S Taylor
CONTEXT: Type 2 diabetes and obesity are risk factors for endometrial hyperplasia and cancer, suggesting that hyperinsulinemia contributes to pathogenesis. Insulin action through insulin receptor (IR) splice variants IR-A and IR-B regulates cellular mitogenesis and metabolism, respectively. OBJECTIVE: We hypothesized that IR-A and IR-B are differentially regulated in normal endometrium, according to mitogenic and metabolic requirements through the menstrual cycle, as well as in endometrial hyperplasia and cancer...
July 2016: Journal of Clinical Endocrinology and Metabolism
S Yu Yuriev, I S Popova, L R Mustafina, I A Zakonova, A E Sazonov, A B Poletaev
The study was carried out to evaluate clinical informativeness ofstudies of immunological parameters of structural and functional elements of endometrium in complex with profile of embritropic autoimmune antibodies under non-carrying of pregnancy The sampling consisted of 19 women of reproductive age with episodes of non-carrying in first semester. They were examined for inherited thrombophilia and profiles of immune reactivity of natural regulatory auto-antibodies (ELI-P-Complex). The biopsy material of endometrium was subjected to histological and immune histochemical (CD16, CD56, CD68, CB138, estrogen and progesterone receptors) analyses...
October 2015: Klinicheskaia Laboratornaia Diagnostika
Jun Ho Kim, Jin Hyup Lee, Young Jun Kim
Bazedoxifene (BZA) is a novel selective estrogen receptor modulator that exhibits estrogen agonist activity in the bone but estrogen antagonist activity in the breast and uterus. We recently demonstrated that BZA mimics estrogenic actions in reversing metabolic abnormalities while protecting the endometrium from estrogen stimulation in ovariectomized (OVX) mice. However, it is unknown whether BZA, alone or paired with estrogens, can protect pancreatic β-cell function or survival. Thus, the aim of this study was to evaluate the preventive effects of estrogens [17β-estradiol or conjugated estrogens (CE)], BZA and their combinations against β-cell failure...
November 6, 2015: Biological & Pharmaceutical Bulletin
Chiara Mannelli, Anna Z Szóstek, Karolina Lukasik, Claudiopietro Carotenuto, Francesca Ietta, Roberta Romagnoli, Cristina Ferretti, Luana Paulesu, Slawomir Wołczynski, Dariusz Jan Skarzynski
The human endometrium is a fertility-determining tissue and a target of steroid hormones' action. Endocrine disruptors (EDs) can exert adverse effects on the physiological function of the decidua at the maternal-fetal interface. We examined the potential effects of an ED, bisphenol A (BPA), on endometrial maturation/decidualization, receptivity, and secretion of decidual factors (biomarkers). In vitro decidualized, endometrial stromal cells from six hysterectomy specimens were treated with 1  pM-1  μM of BPA, for 24  h and assessed for cell viability and proliferation...
August 2015: Reproduction: the Official Journal of the Society for the Study of Fertility
Kyong Hye Joung, Jae-Wook Jeong, Bon Jeong Ku
Type 2 diabetes mellitus (T2DM), a chronic disease increasing rapidly worldwide, is well established as an important risk factor for various types of cancer. Although many factors impact the development of T2DM and cancer including sex, age, ethnicity, obesity, diet, physical activity levels, and environmental exposure, many epidemiological and experimental studies are gradually contributing to knowledge regarding the interrelationship between DM and cancer. The insulin resistance, hyperinsulinemia, and chronic inflammation associated with diabetes mellitus are all associated strongly with cancer...
2015: BioMed Research International
T T Piltonen, J C Chen, M Khatun, M Kangasniemi, A Liakka, T Spitzer, N Tran, H Huddleston, J C Irwin, L C Giudice
STUDY QUESTION: Do endometrial stromal fibroblasts (eSF) in women with polycystic ovary syndrome (PCOS) (eSFpcos) exhibit altered estrogen and/or progesterone (P4) responses, which may explain some of the adverse reproductive outcomes and endometrial pathologies in these women? SUMMARY ANSWER: In vitro, eSF from women with PCOS exhibit an aberrant decidualization response and concomitant changes in pro-inflammatory cytokine, chemokine and matrix metalloproteinase (MMP) release and immune cell chemoattraction...
May 2015: Human Reproduction
Gerlinde R Otti, Leila Saleh, Philipp Velicky, Christian Fiala, Jürgen Pollheimer, Martin Knöfler
Decidualization, the transformation of the human uterine mucosa into the endometrium of pregnancy, is critical for successful implantation and embryonic development. However, key regulatory factors controlling differentiation of uterine stromal cells into hormone-secreting decidual cells have not been fully elucidated. Hence, we herein investigated the role of the Notch signaling pathway in human decidual stromal cells (HDSC) isolated from early pregnancy samples. Immunofluorescence of first trimester decidual tissues revealed expression of Notch2 receptor and its putative, membrane-anchored interaction partners Jagged1, Delta-like (DLL) 1 and DLL4 in stromal cells whereas other Notch receptors and ligands were absent from these cells...
2014: PloS One
Jolanta Kiewisz, Kamil Krawczynski, Pawel Lisowski, Agnieszka Blitek, Lech Zwierzchowski, Adam J Ziecik, Monika M Kaczmarek
The objective of the study was to investigate transcriptomic profile of pig endometrium on Days 12 and 16 of pregnancy in comparison with the respective days of the estrous cycle. Labeled complementary DNA was hybridized to Porcine Long Oligo microarray containing 13,297 oligonucleotide probes, which represented complementary DNA and expressed sequence tags. Statistical analysis revealed 110 differentially expressed genes (DEGs) on Day 12 of pregnancy and 179 DEGs on Day 16 of pregnancy. In silico analysis of gene function and functionality networks revealed links between genes implicated in cell death and survival, protein synthesis, lipid metabolism, cellular movement, tissue development, and cell-to-cell signaling...
October 1, 2014: Theriogenology
Kana Sugawara, Toshio Hamatani, Mitsutoshi Yamada, Seiji Ogawa, Shintaro Kamijo, Naoaki Kuji, Hidenori Akutsu, Kenji Miyado, Yasunori Yoshimura, Akihiro Umezawa
We induced differentiation of human amnion-derived mesenchymal stem cells (AMCs) and menstrual blood-derived mesenchymal stem cells (MMCs) into endometrial stroma-like cells, which could be useful for cell therapy to support embryo implantation. Interestingly, the expression patterns of surface markers were similar among AMCs, MMCs, and endometrial stromal cells. In addition, whereas treatment with estrogen and progesterone was not very effective for decidualizing AMCs and MMCs, treatment with 8-Br-cAMP prompted remarkable morphological changes in these cells as well as increased expression of decidualization markers (prolactin and insulin-like growth factor binding protein-1) and attenuated expression of surface markers unique to mesenchymal stem cells...
2014: Scientific Reports
Qian Zhang, Rosemarie Schmandt, Joseph Celestino, Adrienne McCampbell, Melinda S Yates, Diana L Urbauer, Russell R Broaddus, David S Loose, Gregory L Shipley, Karen H Lu
OBJECTIVE: Obesity-associated hyperestrogenism and hyperinsulinemia contribute significantly to the pathogenesis of endometrial cancer. We recently demonstrated that metformin, a drug long used for treatment of type 2 diabetes, attenuates both insulin- and estrogen-mediated proliferative signaling in the obese rat endometrium. In this study, we sought to identify tissue biomarkers that may prove clinically useful to predict tissue response for both prevention and therapeutic studies. We identified CGRRF1 (cell growth regulator with ring finger domain 1) as a novel metformin-responsive gene and characterized its possible role in endometrial cancer prevention...
April 2014: Gynecologic Oncology
Yuki Ogo, Shusuke Taniuchi, Fumiya Ojima, Sayo Hayashi, Itsuo Murakami, Yuka Saito, Sakae Takeuchi, Toshiyuki Kudo, Sumio Takahashi
Insulin-like growth factor 1 (IGF-1) is involved in regulations of reproductive functions in rats and mice. IGF-1 expression is regulated by estrogen in several reproductive organs including the uterus and ovary. Two types of estrogen receptor (ERα and ERβ) are expressed in mouse uteri and ovaries, and it is unclear whether they differently mediate IGF-1 gene transcription. To clarify the roles of ERα and ERβ, mouse endometrial stromal cells and ovarian granulosa cells were treated with ligands specific for individual estrogen receptors...
2014: Journal of Reproduction and Development
Gustavo Dias Ferreira, Ariane Germeyer, Amanda de Barros Machado, Tadeu Ludwig do Nascimento, Ilma Simoni Brum, Thomas Strowitzki, Helena von Eye Corleta, Edison Capp
OBJECTIVE: To assess the effect of metformin on gene and protein expression of insulin receptor (IR) and IGF-1 (IGF-1R) receptor in human endometrial stromal cells after stimulation with androgen and insulin. STUDY DESIGN: Primary culture of endometrial stromal cells stimulated with estrogen, progesterone with or without androgen or insulin, and treated with metformin for 24 and 48 h, followed by RNA (qRT-PCR) and protein (Western blot) extraction and analysis. RESULTS: IR gene expression was increased after treatment with insulin (2...
August 2014: Archives of Gynecology and Obstetrics
Changhwan Ahn, Hyun Yang, Eui-Ju Hong, Eui-Bae Jeung
The transient receptor potential channels are membrane-binding proteins that are nonselectively permeable for cations, such as Ca(2+) and Mg(2+), in numerous mammalian cells. The extracellular or intracellular ions play key roles in physiological functions including muscle contraction, cytokine production, insulin release, and apoptosis. Although transient receptor potential melastatin (TRPM) channels are implicated in nonreproductive tissues, the presence of TRPM2 has been reported in endometrium of uterus...
October 2014: Reproductive Sciences
Gustavo Dias Ferreira, Ariane Germeyer, Amanda de Barros Machado, Tadeu Ludwig do Nascimento, Thomas Strowitzki, Ilma Simoni Brum, Helena von Eye Corleta, Edison Capp
OBJECTIVE: To assess the effect of metformin on expression of Akt, ERK, PI3K and GLUT4, proteins associated with the growth factor signaling cascade, in human endometrial stromal cells after stimulation with androgen and insulin. STUDY DESIGN: Primary culture of endometrial stromal cells were stimulated in different groups with estrogen, progesterone, androgen and insulin and treated with metformin for 10min, 24h and 48h. After 14 days, proteins were extracted for Western blot analysis...
April 2014: European Journal of Obstetrics, Gynecology, and Reproductive Biology
Yoshie Manabe, Makoto Tochigi, Akiyoshi Moriwaki, Sakae Takeuchi, Sumio Takahashi
Reproductive functions decline with the onset of diabetes in female mice. Diabetic mice have smaller uteri with an underdeveloped endometrium, suggesting diminished estrogen-induced growth. We aimed to clarify the changes in the estrous cycle and in insulin-like growth factor 1 (IGF1) expression in the uteri of streptozotocin (STZ)-treated diabetic mice, because IGF1 is one of the main growth factors involved in estrogen-induced uterine growth. ICR female mice were intraperitoneally administered STZ (10 mg/100 g BW), and blood glucose levels were determined...
2013: Journal of Reproduction and Development
Nuria Eritja, Cristina Mirantes, David Llobet, Andree Yeramian, Laura Bergadà, Mari A Dosil, Mónica Domingo, Xavier Matias-Guiu, Xavier Dolcet
Loss of tumor-suppressor PTEN is the most common alteration in endometrial carcinoma. However, the relationship between loss of PTEN, growth factors [eg, insulin/insulin-like growth factor (IGF)-1], epidermal growth factor (EGF), and hyperestrogenism in the development of endometrial carcinoma is still controversial. By using three-dimensional (3D) cultures of PTEN(+/+) and PTEN(+/-) endometrial epithelial cells, we investigated the effects of EGF, insulin/IGF, and estradiol in endometrial cell proliferation...
July 2013: American Journal of Pathology
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