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

Mus musculus

Project description:Estrogen signaling and fatty liver disease

| PRJNA376559 | ENA

Mus musculus

Project description:Osteoclastic estrogen receptor alpha mediates the osteoprotective estrogen action through Fas ligand signaling

| PRJNA99829 | ENA

RNA sequence data in whole cell extracts of differentiated human podocytes

Project description:Sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is a lipid raft enzyme that regulates plasma membrane (PM) fluidity. Here we report that SMPDL3b excess, as observed in podocytes in diabetic kidney disease (DKD), impairs insulin receptor isoform B-dependent pro-survival insulin signaling by interfering with insulin receptor isoforms binding to caveolin-1 in PM. SMPDL3b excess affects the production of active sphingolipids resulting in decreased ceramide-1-phosphate (C1P) content as observed in human podocytes in vitro and in kidney cortexes of diabetic db/db mice in vivo. Podocyte-specific Smpdl3b deficiency in db/db mice is sufficient to restore kidney cortex C1P content and to protect from DKD. Exogenous administration of C1P restores IR signaling in vitro and prevents established DKD progression in vivo. Taken together, we identified SMPDL3b as a modulator of insulin signaling and demonstrated that supplementation with exogenous C1P may represent a lipid therapeutic strategy to treat diabetic complications such as DKD.

2019-04-12 | GSE129666 | GEO

Aorta- and liver-specific ERalpha binding patterns and gene regulation by estrogen (ChIP-seq)

Project description:Estrogen has vascular protective effects in premenopausal women and in women under 60 receiving hormone replacement therapy. However, estrogen also increases risks of breast and uterine cancers and of venous thromboses linked to upregulation of coagulation factors in the liver. In mouse models, the vasoprotective effects of estrogen are mediated by the estrogen receptor alpha (ERa) transcription factor. Here, through next generation sequencing approaches, we show that almost all of the genes regulated by 17-b-estradiol (E2) differ between mouse aorta and mouse liver, and that this is associated with a distinct genomewide distribution of ERa on chromatin. Bioinformatic analysis of E2-regulated promoters and ERa binding site sequences identify several transcription factors that may determine the tissue specificity of ERa binding and E2-regulated genes, including the enrichment of NFkB, AML1 and AP-1 sites in the promoters of E2 downregulated inflammatory genes in aorta but not liver. The possible vascular-specific functions of these factors suggests ways in which the protective effects of estrogen could be promoted in the vasculature without incurring negative effects in other tissues. Our results also highlight the likely importance of rapid signaling of membrane-associated ERa to cellular kinases (altering the activities of transcription factors other than ER itself) in determining tissue specific transcriptional responses to estrogen. The aortas or liver fragments of wild-type C57/BL6 mice were incubated ex vivo with 10nM E2 or ethanol vehicle for 45 minutes before formaldehyde fixation, harvesting of chromatin & ChIP with anti- mouse estrogen receptor alpha antibodies. Each condition was performed with two biological replicates, and each replicate contained aortas or liver fragments from 5 mice.

2014-06-30 | E-GEOD-52351 | biostudies-arrayexpress

Time-course effect of estradiol and estradiol-BSA on early gene expression in MDA-MB-231 cells

Project description:Estrogens have been reported to activate several processes via membrane binding to either classic estrogen receptors (ERs) or GPR30. We have used either estradiol or BSA-conjugated estradiol in order to initiate membrane-initiated actions and ICI 172,780 (ICI) or G15 to explore ER- and GPR30-related transcription. Our results show that the majority of G15-inhibited transcription is depending on ERs, as it is also inhibited by ICI. However, a small number of transcripts, related to specific actions/pathways is either exclusively inhibited by G15, providing evidence about a specific GPR30 signature, or not inhibited by ICI or G15 suggesting the existence of another, yet unidentified estrogen receptor.

2012-01-01 | GSE32668 | GEO

Time-course effect of estradiol and estradiol-BSA on early gene expression in SKBR3 cells

2012-01-01 | GSE32669 | GEO

Time-course effect of estradiol and estradiol-BSA on early gene expression in T47D cells

2012-01-01 | GSE32666 | GEO