scholarly journals Ginsenoside-Rb1 from Panax ginseng C.A. Meyer Activates Estrogen Receptor-α and -β, Independent of Ligand Binding

2004 ◽  
Vol 89 (7) ◽  
pp. 3510-3515 ◽  
Author(s):  
JungYoon Cho ◽  
Wankyu Park ◽  
SeungKi Lee ◽  
Woongshick Ahn ◽  
YoungJoo Lee
Keyword(s):  
Estrogen Receptor ◽  
Ligand Binding ◽  
Estrogen Receptors ◽  
Panax Ginseng ◽  
Estrogenic Activity ◽  
Specific Binding ◽  
Dependent Manner ◽  
Ginsenoside Rb1 ◽  
17Β Estradiol ◽  
Mcf 7

Abstract We studied the estrogenic activity of a component of Panax ginseng, ginsenoside-Rb1. The activity of ginsenoside-Rb1 was characterized in a transient transfection system, using estrogen receptor isoforms and estrogen-responsive luciferase plasmids, in COS monkey kidney cells. Ginsenoside-Rb1 activated both α and β estrogen receptors in a dose-dependent manner with maximal activity observed at 100 μm, the highest concentration examined. Activation was inhibited by the estrogen receptor antagonist ICI 182,780, indicating that the effects were mediated through the estrogen receptor. Treatment with 17β-estradiol or ginsenoside-Rb1 increased expression of the progesterone receptor, pS2, and estrogen receptor in MCF-7 cells and of AP-1-driven luciferase genes in COS cells. Although these data suggest that it is functionally very similar to 17β-estradiol, ginsenoside-Rb1 failed to displace specific binding of [3H]17β-estradiol from estrogen receptors in MCF-7 whole-cell ligand binding assays. Our results indicate that the estrogen-like activity of ginsenoside-Rb1 is independent of direct estrogen receptor association.

scholarly journals PARP7 and Mono-ADP-Ribosylation Negatively Regulate Estrogen Receptor α Signaling in Human Breast Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 623
Author(s):  
Marit Rasmussen ◽  
Susanna Tan ◽  
Venkata S. Somisetty ◽  
David Hutin ◽  
Ninni Elise Olafsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Protein Modification ◽  
Target Genes ◽  
Estrogen Receptor Α ◽  
Transactivation Domain ◽  
Adp Ribosylation ◽  
Protein Levels ◽  
17Β Estradiol ◽  
Mcf 7

ADP-ribosylation is a post-translational protein modification catalyzed by a family of proteins known as poly-ADP-ribose polymerases. PARP7 (TIPARP; ARTD14) is a mono-ADP-ribosyltransferase involved in several cellular processes, including responses to hypoxia, innate immunity and regulation of nuclear receptors. Since previous studies suggested that PARP7 was regulated by 17β-estradiol, we investigated whether PARP7 regulates estrogen receptor α signaling. We confirmed the 17β-estradiol-dependent increases of PARP7 mRNA and protein levels in MCF-7 cells, and observed recruitment of estrogen receptor α to the promoter of PARP7. Overexpression of PARP7 decreased ligand-dependent estrogen receptor α signaling, while treatment of PARP7 knockout MCF-7 cells with 17β-estradiol resulted in increased expression of and recruitment to estrogen receptor α target genes, in addition to increased proliferation. Co-immunoprecipitation assays revealed that PARP7 mono-ADP-ribosylated estrogen receptor α, and mass spectrometry mapped the modified peptides to the receptor’s ligand-independent transactivation domain. Co-immunoprecipitation with truncated estrogen receptor α variants identified that the hinge region of the receptor is required for PARP7-dependent mono-ADP-ribosylation. These results imply that PARP7-mediated mono-ADP-ribosylation may play an important role in estrogen receptor positive breast cancer.

Partial agonist, but not pure antiestrogens stimulate doming, a marker of normal differentiation, in the MCF-7 breast cancer cell line

2012 ◽  
Vol 12 (3) ◽  
Author(s):  
W. Barkley Butler ◽  
Stephen C. D’Amico ◽  
William J. Glassford ◽  
Weizhen Wu
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Partial Agonist ◽  
Trichostatin A ◽  
Calf Serum ◽  
Cancer Cell Line ◽  
Dependent Manner ◽  
Dome Formation ◽  
Mcf 7

AbstractThe mechanisms by which tamoxifen inhibits breast tumor growth are not completely understood. Partial agonist antiestrogens such as tamoxifen may cause the estrogen receptor (ER) to interact with genes different from those activated by ER bound to estradiol. Doming is a property often associated with, and considered a marker of, differentiation in mammary epithelial cells in culture. This study compared the ability of pure and partial agonist antiestrogens to stimulate doming.MCF-7 cells grown in medium with 10% calf serum were treated with antiestrogens. Domes were counted in three rows (width of the 4× field) across the flask.Three partial agonist antiestrogens [4-hydroxytamoxifen (OHT), H1285 and RU 39,411] caused dome formation. None of the pure antiestrogens tested (ICI 164,384, ICI 182,780 and RU 58,668) caused doming. Doming was stimulated in a dose-dependent manner starting at 1 nM OHT with maximum stimulation at 10–100 nM. Estradiol did not stimulate doming, but blocked doming at 1%–10% of the OHT concentration. Trichostatin A (TSA) reduced the level of estrogen receptor alpha (ERα) and adding it 24 h before adding OHT prevented dome formation.OHT and the other partial agonist antiestrogens appear to act through the ER to stimulate doming. The ability of tamoxifen to induce a marker of differentiation may play a role in its inhibition of breast tumors. If so, then the fact that other partial agonist antiestrogens share this ability, but that pure antiestrogens lack it, may be an important consideration in developing new antiestrogens for breast cancer therapy.

The Influence of 17-Oxo- and 17-Hydroxy-16,17-secoestratriene Derivatives on Estrogen Receptor

2006 ◽  
Vol 71 (4) ◽  
pp. 532-542 ◽  
Author(s):  
Suzana Jovanović-Šanta ◽  
Julijana Petrović ◽  
Marija Sakač ◽  
Zorica Žakula ◽  
Esma Isenović ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Estrogenic Activity ◽  
Total Loss ◽  
The Other ◽  
Binding Parameters ◽  
Antiestrogenic Activity ◽  
Other Hand

Since many of newly synthesised D-secoestratriene derivatives showed antiestrogenic effect, with almost a total loss of estrogenic activity, we studied the effects of some of these compounds on estrogen receptors (ER), the translocation of the estrogen-ER complexes formed in presence of competing substances into the nucleus, as well as the binding of these complexes to DNA. The results of uterotrophic effects of analysed derivatives are in agreement with the influence of these compounds on activity and binding parameters of estrogen receptors. Namely, compounds that show relatively high antiestrogenic activity predominantly increase Kd and inhibit translocation to nuclei of radioactive complexes formed in their presence. On the other hand, compounds that do not significantly change binding parameters of estrogen receptors do not show antiestrogenic effect in in vivo experiments.

scholarly journals Resveratrol Acts as a Mixed Agonist/Antagonist for Estrogen Receptors α and β*

Endocrinology ◽  
2000 ◽  
Vol 141 (10) ◽  
pp. 3657-3667 ◽  
Author(s):  
Jennifer L. Bowers ◽  
Valentyn V. Tyulmenkov ◽  
Sarah C. Jernigan ◽  
Carolyn M. Klinge
Keyword(s):  
Estrogen Receptors ◽  
Transcriptional Activity ◽  
Red Wine ◽  
Dependent Manner ◽  
Agonist Activity ◽  
Epidemiological Evidence ◽  
Pr Genes ◽  
Antagonist Activity ◽  
Cholesterol Levels ◽  
Mcf 7

Abstract Epidemiological evidence indicates that phytoestrogens inhibit cancer formation and growth, reduce cholesterol levels, and show benefits in treating osteoporosis. At least some of these activities are mediated through the interaction of phytoestrogens with estrogen receptors α and β (ERα and ERβ). Resveratrol, trans-3,5,4′-trihydroxystilbene, is a phytoestrogen in grapes that is present in red wine. Resveratrol was shown to bind ER in cytosolic extracts from MCF-7 and rat uteri. However, the contribution of ERα vs. ERβ in this binding is unknown. Here we report that resveratrol binds ERβ and ERα with comparable affinity, but with 7,000-fold lower affinity than estradiol (E2). Thus, resveratrol differs from other phytoestrogens that bind ERβ with higher affinity than ERα. Resveratrol acts as an estrogen agonist and stimulates ERE-driven reporter gene activity in CHO-K1 cells expressing either ERα or ERβ. The estrogen agonist activity of resveratrol depends on the ERE sequence and the type of ER. Resveratrol-liganded ERβ has higher transcriptional activity than E2-liganded ERβ at a single palindromic ERE. This indicates that those tissues that uniquely express ERβ or that express higher levels of ERβ than ERα may be more sensitive to resveratrol’s estrogen agonist activity. For the natural, imperfect EREs from the human c-fos, pS2, and progesterone receptor (PR) genes, resveratrol shows activity comparable to that induced by E2. We report that resveratrol exhibits E2 antagonist activity for ERα with select EREs. In contrast, resveratrol shows no E2 antagonist activity with ERβ. These data indicate that resveratrol differentially affects the transcriptional activity of ERα and ERβ in an ERE sequence-dependent manner.

Binding of Phytoestrogens to Rat Uterine Estrogen Receptors and Human Sex Hormone-binding Globulins

2005 ◽  
Vol 60 (7-8) ◽  
pp. 649-656 ◽  
Author(s):  
Pablo Ibieta Hillerns ◽  
Yuangang Zu ◽  
Michael Wink
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Conformational Changes ◽  
Nordihydroguaiaretic Acid ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Scatchard Analysis ◽  
Binding Affinities ◽  
Hormone Binding ◽  
17Β Estradiol

The interaction of phytoestrogens with the most important binding sites of steroid hormones, i.e. sex hormone-binding globulin and estrogen receptors, was investigated. Relative binding affinities and association constants for 21 compounds among them isoflavones, flavones, flavonols, flavanones, chalcones and lignans were determined. The lignan nordihydroguaiaretic acid weakly displaced 17β-[3H]-estradiol from estrogen receptor and Scatchard analysis suggests non-conformational changes. Compounds from Glycyrrhiza glabra, liquiritigenin and isoliquiritigenin, showed estrogenic affinities to both receptors. 18β-Glycyrrhetinic acid displaced 17β-[3H]-estradiol from sex hormone-binding globulin but not from the estrogen receptor. Phytoestrogens compete with 17β-estradiol much stronger than with 5α-dihydrotestosterone for binding to sex hormone-binding globulin.

Design, Synthesis, and Estrogenic Activity of a Novel Estrogen Receptor ModulatorA Hybrid Structure of 17β-Estradiol and Vitamin E in Hippocampal Neurons

2007 ◽  
Vol 50 (18) ◽  
pp. 4471-4481 ◽  
Author(s):  
Liqin Zhao ◽  
Chunyang Jin ◽  
Zisu Mao ◽  
Madathil B. Gopinathan ◽  
Kenneth Rehder ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Vitamin E ◽  
Hippocampal Neurons ◽  
Estrogenic Activity ◽  
Hybrid Structure ◽  
Design Synthesis ◽  
17Β Estradiol

scholarly journals Palmitoylation-dependent Estrogen Receptor α Membrane Localization: Regulation by 17β-Estradiol

2005 ◽  
Vol 16 (1) ◽  
pp. 231-237 ◽  
Author(s):  
Filippo Acconcia ◽  
Paolo Ascenzi ◽  
Alessio Bocedi ◽  
Enzo Spisni ◽  
Vittorio Tomasi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Plasma Membrane ◽  
Estrogen Receptor Α ◽  
Membrane Localization ◽  
Target Cells ◽  
Dependent Manner ◽  
Caveolin 1 ◽  
17Β Estradiol

A fraction of the nuclear estrogen receptor α (ERα) is localized to the plasma membrane region of 17β-estradiol (E2) target cells. We previously reported that ERα is a palmitoylated protein. To gain insight into the molecular mechanism of ERα residence at the plasma membrane, we tested both the role of palmitoylation and the impact of E2 stimulation on ERα membrane localization. The cancer cell lines expressing transfected or endogenous human ERα (HeLa and HepG2, respectively) or the ERα nonpalmitoylable Cys447Ala mutant transfected in HeLa cells were used as experimental models. We found that palmitoylation of ERα enacts ERα association with the plasma membrane, interaction with the membrane protein caveolin-1, and nongenomic activities, including activation of signaling pathways and cell proliferation (i.e., ERK and AKT activation, cyclin D1 promoter activity, DNA synthesis). Moreover, E2 reduces both ERα palmitoylation and its interaction with caveolin-1, in a time- and dose-dependent manner. These data point to the physiological role of ERα palmitoylation in the receptor localization to the cell membrane and in the regulation of the E2-induced cell proliferation.

scholarly journals Estrogenic Activity of Mycoestrogen (3β,5α,22E)-Ergost-22-en-3-ol via Estrogen Receptor α-Dependent Signaling Pathways in MCF-7 Cells

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 36
Author(s):  
Dahae Lee ◽  
Yuri Ko ◽  
Changhyun Pang ◽  
Yoon-Joo Ko ◽  
You-Kyoung Choi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Methanol Extract ◽  
Estrogenic Activity ◽  
Cancer Cell Line ◽  
Estrogen Receptor Α ◽  
Bile Secretion ◽  
Bioassay Guided Fractionation ◽  
Positive Breast Cancer Cell ◽  
Mcf 7

Armillariella tabescens (Scop.) Sing., a mushroom of the family Tricholomataceae, has been used in traditional oriental medicine to treat cholecystitis, improve bile secretion, and regulate bile-duct pressure. The present study evaluated the estrogen-like effects of A. tabescens using a cell-proliferation assay in an estrogen-receptor-positive breast cancer cell line (MCF-7). We found that the methanol extract of A. tabescens fruiting bodies promoted cell proliferation in MCF-7 cells. Using bioassay-guided fractionation of the methanol extract and chemical investigation, we isolated and identified four steroids and four fatty acids from the active fraction. All eight compounds were evaluated by E-screen assay for their estrogen-like effects in MCF-7 cells. Among the tested isolates, only (3β,5α,22E)-ergost-22-en-3-ol promoted cell proliferation in MCF-7 cells; this effect was mitigated by the ER antagonist, ICI 182,780. The mechanism underlying the estrogen-like effect of (3β,5α,22E)-ergost-22-en-3-ol was evaluated using Western blot analysis to detect the expression of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), Akt, and estrogen receptor α (ERα). We found that (3β,5α,22E)-ergost-22-en-3-ol induced an increase in phosphorylation of ERK, PI3K, Akt, and ERα. Together, these experimental results suggest that (3β,5α,22E)-ergost-22-en-3-ol is responsible for the estrogen-like effects of A. tabescens and may potentially aid control of estrogenic activity in menopause.

scholarly journals Sex- and Age-Related Estrogen Signaling Alteration in Inflammatory Bowel Diseases: Modulatory Role of Estrogen Receptors

2019 ◽  
Vol 20 (13) ◽  
pp. 3175 ◽  
Author(s):  
Damian Jacenik ◽  
Adam I. Cygankiewicz ◽  
Anna Mokrowiecka ◽  
Ewa Małecka-Panas ◽  
Jakub Fichna ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Inflammatory Bowel Diseases ◽  
Protein Level ◽  
Estrogen Signaling ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Age Related ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The pathogenesis of inflammatory bowel diseases (IBD) seems to be associated with alterations of immunoregulation. Several lines of evidence suggest that estrogens play a role in the modulation of immune responses and may be related to the etiology of IBD. The purpose of this work was to examine the involvement of G protein-coupled estrogen receptor (GPER), estrogen receptor α (ERα), estrogen receptor β (ERβ) and ERα spliced variants ERα36 and ERα46 in Crohn’s disease (CD) and ulcerative colitis (UC). The studied group included 73 patients with IBD and 31 sex and age-related controls. No differences in serum levels of 17β-estradiol nor of CYP1A1 and SULT1E1 enzymes involved in estrogen catabolism were stated. The expression pattern of estrogen receptors in tissue samples was quantified using real-time PCR and Western blotting. Statistically significant up-regulation of GPER and ERα in both CD and UC as well as down-regulation of ERβ in CD patients was found. However, differences in the expression of estrogen receptors in CD and UC have been identified, depending on the sex and age of patients. In men, up-regulation of GPER, ERα and ERα46 expression was shown in CD and UC patients. In women under 50 years of age, GPER protein level increased in UC whereas ERβ expression tended to decrease in CD and UC patients. In turn, in women over 50 the protein level of ERα increased in UC while ERβ expression decreased in CD patients. Dysregulation of estrogen receptors in the intestinal mucosa of patients with CD and UC indicates that estrogen signaling may play a role in the local immune response and maintain epithelial homeostasis in a gender- and age-dependent manner.

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