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Insulin receptor endometrium

L Oróstica, I Astorga, F Plaza-Parrochia, C Vera, V García, R Carvajal, F Gabler, C Romero, M Vega
BACKGROUND/OBJECTIVES: A high percentage of women having PCOS exhibit hyperinsulinemia and obesity. Transforming necrosis factor-alpha (TNF-α) is an adipokine that increases in obesity and negatively affects insulin action in several tissues, including the endometrium. In fact, it has been reported that insulin signaling is altered in the endometrium of PCOS women, affecting its reproductive function. The aim of this study was to determine the pro-inflammatory environment and TNF-α signaling in endometrium from obese women with PCOS, and also to evaluate the effect of TNF-α on endometrial cell energy homeostasis...
August 29, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Yue Jiang, Ruiwei Jiang, Xi Cheng, Qun Zhang, Yali Hu, Hui Zhang, Yun Cao, Mei Zhang, Junxia Wang, Lijun Ding, Zhenyu Diao, Haixiang Sun, Guijun Yan
STUDY QUESTION: How do NR4A receptors drive decidualization of human endometrial stromal cells (hESCs)? SUMMARY ANSWER: NR4A receptors modulate endometrial decidualization by transcriptional activation of FOXO1A, and in adenomyosis patients, the reduced expression of NR4A receptors in the eutopic endometrium may represent a novel mechanism to explain impaired decidualization and subfertility. WHAT IS KNOWN ALREADY: A close relationship between impaired decidualization and subfertility has been established...
September 2016: Molecular Human Reproduction
N Smolinska, K Dobrzyn, M Kiezun, K Szeszko, A Maleszka, T Kaminski
Adiponectin and its receptors are expressed in the human and porcine uterus and this endocrine system has important role in the regulation of reproductive processes. The expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (HSD3B1) were observed in the human and porcine uterus during the oestrous cycle and pregnancy. The de novo synthesis of steroids in the uterus might be a crucial factor for effective implantation and maintenance of pregnancy. We hypothesized that adiponectin modulates the expression of key enzymes in the synthesis of the steroids: StAR, P450 side chain cleavage enzyme (CYP11A1) and HSD3B1, as well as progesterone (P4) and androstenedione (A4) secretion by the porcine uterus...
June 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
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
Yuping Zhang, Renee Goodfellow, Yujun Li, Shujie Yang, Christopher J Winters, Kristina W Thiel, Kimberly K Leslie, Baoli Yang
OBJECTIVE: The PI3K/Akt pathway is frequently dysregulated in endometrial cancer, the most common gynecologic malignancy. Emerging evidence identifies the ubiquitin ligase NEDD4 as a key regulator of the PI3K/Akt pathway via activation of insulin-like growth factor-1 receptor (IGF-1R). Our objective was to understand the role of NEDD4 in endometrial cancer. METHODS: NEDD4 expression was assessed by immunohistochemistry in a tissue microarray with 77 endometrial lesions ranging from normal benign endometrium to tumor specimens of varying stage and grade...
October 2015: Gynecologic Oncology
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
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
Silvia Gamundi-Segura, Jose Serna, Sergio Oehninger, Jose A Horcajadas, Jose M Arbones-Mainar
Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines...
September 2015: Journal of Physiology and Biochemistry
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
Akiko Ito-Yamaguchi, Ryota Suganuma, Atsuko Kumagami, Shigeatsu Hashimoto, Hiromi Yoshida-Komiya, Keiya Fujimori
OBJECTIVE: To evaluate effects of metformin on endocrine, metabolic parameters and endometrial androgen receptor (AR) expression in polycystic ovary syndrome (PCOS). DESIGN: Prospective observational study. METHODS: We analyzed blood samples from 10 PCOS patients, of whom endometrium was also analyzed in five patients. Before and after three months of metformin treatment, endocrine, glucose metabolic parameters and the endometrial AR expressions were assessed...
January 2015: Gynecological Endocrinology
K L Roemer, S L Young, R F Savaris
CONTEXT: In a previous microarray analysis, GRB2-associated binding protein 1 (GAB1), a docking protein closely related to the insulin receptor substrate, was down-regulated in endometrium of women with polycystic ovary syndrome (PCOS). OBJECTIVE: The objective of the study was to characterize the cyclic expression of endometrial GAB1 in vivo in normal women and those with PCOS as well as investigate the possible mechanisms of endometrial regulation of GAB1 expression and action in vitro...
November 2014: Journal of Clinical Endocrinology and Metabolism
D Ujvari, M Hulchiy, A Calaby, Å Nybacka, B Byström, A L Hirschberg
STUDY QUESTION: Does lifestyle intervention aiming at weight loss influence endometrial insulin signaling in overweight/obese women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Lifestyle intervention up-regulates, both at the mRNA and protein levels, components of insulin signaling in the endometrium of overweight/obese PCOS women, in relation to an improved menstrual pattern. WHAT IS KNOWN ALREADY: PCOS is a multifactorial endocrine disorder diagnosed by two of the following three criteria: chronic anovulation, hyperandrogenism and polycystic ovaries...
July 2014: Human Reproduction
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
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