Estren Behaves as a Weak Estrogen Rather than a Non-genomic Selective Activator in the Mouse Uterus
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE4615 | GEO | 2006/04/07
SECONDARY ACCESSION(S): PRJNA95323
REPOSITORIES: GEO
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Project description:A proposed membrane-mediated mechanism of rapid non genomic response to estrogen has been the intense focus of recent research. Estren (Es), a synthetic steroid, is reported to act selectively through a rapid membrane-mediated pathway, rather than through the classical nuclear estrogen receptor (ER)-mediated pathway, to maintain bone density in ovaierectomized mice without uterotropic effects. To further evaluate the mechanism and physiological effects of Es we studied responses in adult ovariectomized mice. Experiment Overall Design: Mice were treated with sesame oil vehicle (Sigma), E2 (Steraloids; 1 µg/mouse) estren (300 µg/mouse), or dihydrotestosterone (DHT, Steraloids; 50 µg/mouse) and uteri were collected 2 or 24 hours after treatment and snap frozen in liquid nitrogen. Three or four uteri from each treatment group were pooled and RNA was prepared using Trizol reagent (Invitrogen, Carlsbad CA) and the RNeasy clean up protocol (Qiagen Valencia CA). Gene expression profiling was conducted using Agilent Mouse Oligo arrays with ~20,000 genes represented (Agilent Technologies, Palo Alto, CA). Five hundred ng of total RNA was amplified and labeled using the Agilent Low RNA Input Fluorescent Linear Amplification Kit according to manufacturer's protocol. For each two color comparison, 750 ng of each Cy3- and Cy5-labeled cRNA were mixed and fragmented using the Agilent In Situ Hybridization Kit protocol. Hybridizations were performed for 17 hours in a rotating hybridization oven according to the Agilent 60-mer oligo microarray processing protocol prior to washing and scanning with an Agilent Scanner (Agilent Technologies, Wilmington, DE). Each sample pair was hybridized on 2 replicate chips. Experiment Overall Design: Data was obtained using the Agilent Feature Extraction software (v7.5, v8.1), using defaults for all parameters.
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Project description:This SuperSeries is composed of the following subset Series: GSE13858: Global survey of miRNA microarray of uterus, ovariectomized female mice with or without estrogen (E2) treatment GSE13859: Global survey of miRNA microarray of whole embryo, wild type vs estrogen receptor alpha knockout mice Refer to individual Series
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Project description:Membrane estrogen receptor (ER) alpha stimulates AMP kinase to suppress SREBP1 processing and lipids in liver Here we present evidence that signaling from membrane-localized ERalpha similarly suppresses a subset of mRNAs in the livers of female WT and membrane only estrogen receptor (MOER) transgenic mice but not in estrogen receptor knock out (ERKO) mice Three month old wild type, MOER and ERKO mice were ovariectomized and utilized per IRB-approved. Following ovariectomy and recovery the animals were injected intraperitoneally with PPT (100 ?g) or oil placebo (0.1 mL) daily for 3 days. Whole livers were removed upon euthanasia.
2013-05-14 | E-GEOD-45346 | biostudies-arrayexpress
Project description:Females were ovariectomized and injected with saline estradiol or estriol. Uterine tissue was collected after 2 or 24 hours. RNA was analyzed by microarray compare ealry and late responses to a potent and a weak estrogen agaonist.
2010-09-09 | GSE23241 | GEO
Project description:Females were ovariectomized and injected with saline estradiol or estriol. Uterine tissue was collected after 2 or 24 hours. RNA was analyzed by microarray compare ealry and late responses to a potent and a weak estrogen agaonist. 3 uteri per group were analyzed individually on one-color Agilent arrays.
2010-09-08 | E-GEOD-23241 | biostudies-arrayexpress
Project description:There are concerns regarding possible reproductive toxicity from consumption of soy including an increased risk of endometriosis and endometrial cancer. We used global uterine gene expression profiles in adult ovariectomized (OVX) female rats assessed by RNAseq to examine the estrogenicity of soy protein isolate (SPI) and the potential for feeding SPI to alter estrogen signaling in the uterus. Rats were fed AIN93G diets made with casein (CAS) or SPI from postnatal day (PND) 30. Rats were OVX on PND 50 and infused with 17 beta-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05) and significantly altered expression of 2084 uterine genes. In contrast, SPI feeding had no effect on uterine weight and only altered expression of 177 genes. Overlap between E2 and SPI genes was limited to 69 genes (3%). GO analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of ER alpha to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were cancer pathways and extracellular organization. SPI feeding up-regulated uterine PPAR signaling and fatty acid metabolism. The combination of E2 and SPI feeding resulted in significant regulation of 715 fewer genes relative to E2 alone. In a separate experiment, the combination of E2 and SPI reversed the ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA). These data suggest SPI does not act as a weak estrogen in the uterus but appears to be a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and to be anti-estrogenic in the presence of endogenous estrogens. Rat uterus mRNA of ovariectomized adult female rats subject to four different diets (Caseine, Caseine + E2, Soy and Soy+E2 ) were sequenced, in triplicate, in an Illumina GAIIx sequencer.
2015-06-13 | E-GEOD-69819 | biostudies-arrayexpress
Project description:The uterus, a female reproductive organ regulated by the sex hormones estrogen and progesterone, undergoes periodic cyclical changes. The estrous cycle refers to the reproductive cycle in non-primate mammalian females. During the mouse estrous cycle, the uterus undergoes various physiological changes as a result of dynamic hormonal changes. Accurate regulation of these changes is crucial for the establishment of a successful pregnancy. Notably, estrogen plays an important role in the regulation of the proestrus and estrus stages of the estrous cycle. Family with sequence similarity 3 (Fam3) is a cytokine-like gene family with four members: Fam3a, Fam3b, Fam3c, and Fam3d. Expression and regulation of the Fam3 family members in mouse uterine physiology remain largely unknown. Therefore, this study aimed to investigate the expression of Fam family members in the uterus during the estrous cycle and evaluate its regulation by estrogen using a mouse model. Analysis of mouse uterine RNA sequencing data revealed upregulated expression of Fam3b, Fam3c, and Fam3d during the proestrus and estrus stages. Fam3d expression was dynamically regulated during the estrous cycle, with high expression levels during the proestrus and estrus stages. To investigate whether Fam3d expression is regulated by estrogen, we administered estradiol (E2) to ovariectomized mice at different time points. Fam3d expression was highest 24 h after E2 injection, suggesting that estrogen plays a crucial role in regulating Fam3d expression. Furthermore, inhibition experiments using the estrogen receptor alpha (ERα) antagonist ICI revealed that estrogen regulates Fam3d expression through the ERα-mediated pathway. Immunofluorescence staining demonstrated that FAM3D was exclusively expressed in the luminal and glandular epithelia but not in the stroma. Additionally, FAM3D was predominantly localized in the cytoplasm, particularly in the apical region, and not in the nucleus. These findings provide valuable insights into the potential role of Fam3d in the uterus and lay the groundwork for future research on its function and significance in uterine physiology.
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Project description:Estrogen receptor alpha (ERa) is required for the protective effects of 17-beta-estradiol (E2, the active, endogenous form of estrogen) after vascular injury or in atherosclerosis. E2-bound ERa can function as a transcription factor which binds directly to chromatin (the genomic pathway). Some ERa is also associated with the plasma membrane and, when bound by E2, activates cellular kinases, including PI3K, Akt and ERK (the rapid signaling pathway). Rapid signaling is mediated by interaction between ERa and the adaptor molecule striatin. Here we identify a triple point mutation (AA 231,233 & 234 KRR->AAA) of full length ERa that blocks its association with striatin and eliminates its ability to perform rapid signaling (without affecting its ability to perform genomic signaling). We have created stably-transfected human vascular endothelial cell lines expressing either WT ERa (WT ECs) or KRR mutant ERa (KRR ECs), and use these cells to show that rapid signaling through ERa is required for the proper regulation of most E2-regulated genes (the data presented in this record), and also for the ability of E2 to stimulate EC migration and proliferation and to inhibit inflammatory monocyte adhesion to ECs. Human Eahy 926 stable cell lines carrying a full length wild-type human estrogen receptor alpha (ERa) expression vector (WT ECs) or a full length KRR mutant ERa expression vector (KRR ECs, where the KRR mutant ERa is deficient in rapid signaling) were treated with or without 17-b-estradiol (E2) for 16 hrs. RNA from 3 bioligical replicates per condition was harvested and used to probe Illumina bead arrays.
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Project description:Neuropeptide Y (NPY) is an endogenous modulator of neuronal activity by regulating GABA and glutamate release. Previously, we found that estradiol modulates NPY expression in the hippocampal dentate gyrus. Here we investigated which estrogen receptor type activation is required for the NPY expression. Further, we determined effects of estrogen receptor activation on NPY release. Finally, we determined the contribution of estrogen-mediated remodeling of the GABAergic and glutamatergic network in relation to changes in coupling with NPY in ovariectomized rats. We found that activation of either estrogen receptor type increases NPY expression as well as NPY release in the dentate gyrus. We also found that compared to OVX rats, estrogen replacement increases the likeness of synergistic/antagonistic coupling between the NPY and GABAergic synapse genes while the glutamatergic synapse genes are less likely coupled with NPY. The data together suggest that estrogen plays a critical role in regulation of activity of the NPY system and its coupling to GABAergic and glutamatergic synapses in female rat dentate gyrus. Two-conditions (E = beta-estradiol replacement vs O = oil) experiment. Biological replicates: 4E, 4O.
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Project description:Neuropeptide Y (NPY) is an endogenous modulator of neuronal activity by regulating GABA and glutamate release. Previously, we found that estradiol modulates NPY expression in the hippocampal dentate gyrus. Here we investigated which estrogen receptor type activation is required for the NPY expression. Further, we determined effects of estrogen receptor activation on NPY release. Finally, we determined the contribution of estrogen-mediated remodeling of the GABAergic and glutamatergic network in relation to changes in coupling with NPY in ovariectomized rats. We found that activation of either estrogen receptor type increases NPY expression as well as NPY release in the dentate gyrus. We also found that compared to OVX rats, estrogen replacement increases the likeness of synergistic/antagonistic coupling between the NPY and GABAergic synapse genes while the glutamatergic synapse genes are less likely coupled with NPY. The data together suggest that estrogen plays a critical role in regulation of activity of the NPY system and its coupling to GABAergic and glutamatergic synapses in female rat dentate gyrus.
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