scholarly journals Estrogenic Activities of Fatty Acids and a Sterol Isolated from Royal Jelly

2008 ◽  
Vol 5 (3) ◽  
pp. 295-302 ◽  
Author(s):  
Kazu-Michi Suzuki ◽  
Yoichiro Isohama ◽  
Hiroe Maruyama ◽  
Yayoi Yamada ◽  
Yukio Narita ◽  
...  
Keyword(s):  
Royal Jelly ◽  
Binding Assay ◽  
Estrogenic Activity ◽  
Luminal Epithelium ◽  
Concomitant Treatment ◽  
Decenoic Acid ◽  
Estrogen Responsive Element ◽  
17Β Estradiol ◽  
Responsive Element ◽  
Mcf 7

We have previously reported that royal jelly (RJ) from honeybees (Apis mellifera) has weak estrogenic activity mediated by interaction with estrogen receptors that leads to changes in gene expression and cell proliferation. In this study, we isolated four compounds from RJ that exhibit estrogenic activity as evaluated by a ligand-binding assay for the estrogen receptor (ER) β. These compounds were identified as 10-hydroxy-trans-2-decenoic acid, 10-hydroxydecanoic acid,trans-2-decenoic acid and 24-methylenecholesterol. All these compounds inhibited binding of 17β-estradiol to ERβ, although more weakly than diethylstilbestrol or phytoestrogens. However, these compounds had little or no effect on the binding of 17β-estradiol to ERα. Expression assays suggested that these compounds activated ER, as evidenced by enhanced transcription of a reporter gene containing an estrogen-responsive element. Treatment of MCF-7 cells with these compounds enhanced their proliferation, but concomitant treatment with tamoxifen blocked this effect. Exposure of immature rats to these compounds by subcutaneous injection induced mild hypertrophy of the luminal epithelium of the uterus, but was not associated with an increase in uterine weight. These findings provide evidence that these compounds contribute to the estrogenic effect of RJ.

scholarly journals Real-Time Challenging of ERα Y537S Mutant Transcriptional Activity in Living Cells

Endocrines ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 54-64
Author(s):  
Manuela Cipolletti ◽  
Sara Pescatori ◽  
Filippo Acconcia
Keyword(s):  
Cell Line ◽  
Transcriptional Activity ◽  
Estrogen Receptor Α ◽  
Living Cells ◽  
Patient Treatment ◽  
Estrogen Responsive Element ◽  
Specific Proteins ◽  
Responsive Element ◽  
Mcf 7

Metastatic estrogen receptor α (ERα)-expressing breast cancer (BC) occurs after prolonged patient treatment with endocrine therapy (ET) (e.g., aromatase inhibitors—AI; 4OH-tamoxifen—4OH-Tam). Often these metastatic BCs express a mutated ERα variant (e.g., Y537S), which is transcriptionally hyperactive, sustains uncontrolled proliferation, and renders tumor cells insensitive to ET drugs. Therefore, new molecules blocking hyperactive Y537S ERα mutation transcriptional activity are requested. Here we generated an MCF-7 cell line expressing the Y537S ERα mutation stably expressing an estrogen-responsive element (ERE) promoter, which activity can be monitored in living cells. Characterization of this cell line shows both hyperactive basal transcriptional activity with respect to normal MCF-7 cells, which stably express the same ERE-based promoter and a decreased effect of selective ER downregulators (SERDs) in reducing Y537S ERα mutant transcriptional activity with respect to wild type ERα transcriptional activity. Kinetic profiles of Y537S ERα mutant-based transcription produced by both drugs inducing receptor degradation and siRNA-mediated depletion of specific proteins (e.g., FOXA1 and caveolin1) reveals biphasic dynamics of the inhibition of the receptor-regulated transcriptional effects. Overall, we report a new model where to study the behavior of the Y537S ERα mutant that can be used for the identification of new targets and pathways regulating the Y537S ERα transcriptional activity.

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 Activation of Antimetastatic Nm23-H1 Gene Expression by Estrogen and Its α-Receptor

Endocrinology ◽  
2002 ◽  
Vol 143 (2) ◽  
pp. 467-475 ◽  
Author(s):  
Kwang-Huei Lin ◽  
Won-Jing Wang ◽  
Yi-Hsin Wu ◽  
Sheue-Yann Cheng
Keyword(s):  
Promoter Region ◽  
Tumor Metastasis ◽  
High Avidity ◽  
Carcinoma Cell Lines ◽  
Estrogen Responsive Element ◽  
Breast Carcinoma Cell Lines ◽  
Responsive Element ◽  
Different Levels ◽  
Mcf 7

Abstract Metastasis of various malignant cells is inversely related to the abundance of the Nm23-H1 protein. The role of estrogens in tumor metastasis has now been investigated by examining the effect of E2 on the expression of the Nm23-H1 gene. Three human breast carcinoma cell lines, in which endogenous ERα is expressed at different levels, were used as a tool to assess the role of ERα in Nm23-H1 gene-mediated metastasis. E2 induced time-dependent increases in the abundance of Nm23-H1 mRNA and protein, with the extent of these effects correlating with the level of expression of ERα. E2 induced a marked decrease in the invasive activity of MCF-7 and BT-474 cells but had no effect on BCM-1 cells, which had virtually no ERα. Consistent with these results, the ER-mediated Nm23-H1 promoter activity was inhibited 3-fold by the E2 antagonist, ICI 182,780. Deletion analysis of the promoter region of the Nm23-H1 gene identified a positive estrogen-responsive element located in −108/−94. ER protein bound specifically to the −108/−79 fragment with high avidity. These results indicate that E2, acting through ERα, activated transcription of the Nm23-H1 gene via a positive estrogen-responsive element in the promoter region of the gene. These results suggest that E2 could suppress tumor metastasis by activating the expression of the Nm23-H1 gene.

scholarly journals 17β-Estradiol Inhibits Iron Hormone Hepcidin Through an Estrogen Responsive Element Half-Site

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3170-3178 ◽  
Author(s):  
Qing Yang ◽  
Jinlong Jian ◽  
Stuart Katz ◽  
Steven B. Abramson ◽  
Xi Huang
Keyword(s):  
Hepg2 Cells ◽  
Gene Knockout ◽  
Negative Regulator ◽  
Estrogen Responsive Element ◽  
Gene Knockout Mice ◽  
17Β Estradiol ◽  
Responsive Element ◽  
Hepcidin Gene ◽  
Hepcidin Mrna ◽  
Half Site

Interaction of estrogen with iron at the systemic level is long suspected, but direct evidence linking the two is limited. In the present study, we examined the effects of 17β-estradiol (E2) on hepcidin, a key negative regulator of iron absorption from the liver. We found that transcription of hepcidin was suppressed by E2 treatment in human liver HuH7 and HepG2 cells, and this down-regulation was blocked by E2 antagonist ICI 182780. Chromatin immunoprecipitation, deletion, and EMSA detected a functional estrogen responsive element half-site that is located between −2474 and −2462 upstream from the start of transcription of the hepcidin gene. After cloning the human hepcidin promoter into the pGL3Luc-Reporter vector, luciferase activity was also down-regulated by E2 treatment in HepG2 cells. E2 reduced hepcidin mRNA in wild-type mice as well as in hemochromatosis Fe gene knockout mice. In summary, our data suggest that hepcidin inhibition by E2 is to increase iron uptake, a mechanism to compensate iron loss during menstruation. This mechanism may also contribute to increased iron stores in oral contraceptive users.

scholarly journals Single-Chain Estrogen Receptors (ERs) Reveal that the ERα/β Heterodimer Emulates Functions of the ERα Dimer in Genomic Estrogen Signaling Pathways

2004 ◽  
Vol 24 (17) ◽  
pp. 7681-7694 ◽  
Author(s):  
Xiaodong Li ◽  
Jing Huang ◽  
Ping Yi ◽  
Robert A. Bambara ◽  
Russell Hilf ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Mammalian Cells ◽  
Target Genes ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Single Chain ◽  
Estrogen Responsive Element ◽  
17Β Estradiol ◽  
Responsive Element

ABSTRACT The effects of estrogens, particularly 17β-estradiol (E2), are mediated by estrogen receptor α (ERα) and ERβ. Upon binding to E2, ERs homo- and heterodimerize when coexpressed. The ER dimer then regulates the transcription of target genes through estrogen responsive element (ERE)-dependent and -independent pathways that constitute genomic estrogen signaling. Although ERα and ERβ have similar ERE and E2 binding properties, they display different transregulatory capacities in both ERE-dependent and -independent signaling pathways. It is therefore likely that the heterodimerization provides novel functions to ERs by combining distinct properties of the contributing partners. The elucidation of the role of the ER heterodimer is critical for the understanding of physiology and pathophysiology of E2 signaling. However, differentially determining target gene responses during cosynthesis of ER subtypes is difficult, since dimers formed are a heterogeneous population of homo- and heterodimers. To circumvent the pivotal dimerization step in ER action and hence produce a homogeneous ER heterodimer population, we utilized a genetic fusion strategy. We joined the cDNAs of ERα and/or ERβ to produce single-chain ERs to simulate the ER homo- and heterodimers. The fusion ERs interacted with ERE and E2 in a manner similar to that observed with the ER dimers. The homofusion receptors mimicked the functions of the parent ER dimers in the ERE-dependent and -independent pathways in transfected mammalian cells, whereas heterofusion receptors emulated the transregulatory properties of the ERα dimer. These results suggest that ERα is the functionally dominant partner in the ERα/β heterodimer.

scholarly journals 17β-estradiol binding to ERα promotes the progression of prolactinoma through estrogen-response element-induced CaBP-9k up-regulation

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Jun Liu ◽  
Hao Han ◽  
Wenpeng Lu ◽  
Gaoyang Fan
Keyword(s):  
Cell Apoptosis ◽  
Cell Counting ◽  
Transcriptional Level ◽  
Calbindin D9k ◽  
Estrogen Response ◽  
Estrogen Responsive Element ◽  
Gene Reporter Assay ◽  
17Β Estradiol ◽  
Responsive Element ◽  
Luciferase Gene Reporter Assay

Abstract 17β-estradiol (E2) is considered to be an important instigator of prolactinoma, and can positively regulate the expression of calbindin-D9k (CaBP-9k) which contains an estrogen responsive element (ERE) via estrogen receptors (ERs). However, the detailed mechanism of E2 in promoting CaBP-9k expression and their roles in prolactinoma progression remain unclear. Here, we aimed to characterize it. The luciferase gene reporter assay with luc-ERE transfection showed that E2 treatment significantly enhanced the transcriptional level of CaBP-9k, whereas CaBP-9k activity was reduced when GH3 and MMQ cells were treated with AZD9496, an antagonist of ERα. E2 treatment increased the protein expressions of CaBP-9k and ERα but not ERβ, whereas this effect was also abolished when cells were treated with AZD9496. Besides, immunoprecipitation (IP) and immunofluorescence assays demonstrated that CaBP-9k could directly interact with ERα not ERβ, and Chromatin IP (ChIP) assay showed that ERα could bind to ERE of the CaBP-9k promoter. Moreover, cell counting kit-8 (CCK-8) and flow cytometry assays showed that E2 treatment significantly enhanced cell viability and inhibited cell apoptosis, but these effects were all abolished when ERα was down-regulated by short hairpin RNA (shRNA) or inhibited by AZD9496, as well as CaBP-9K suppression in both GH3 and MMQ cell lines. Taken together, these findings indicated that E2 stimulation promoted prolactin cell proliferation and inhibited cell apoptosis through ERα-induced CaBP-9k up-regulation, which then accelerated the advanced progression of prolactinoma.

scholarly journals 17β-Estradiol Inhibits Apoptosis in MCF-7 Cells, Inducing bcl-2 Expression via Two Estrogen-Responsive Elements Present in the Coding Sequence

2000 ◽  
Vol 20 (8) ◽  
pp. 2890-2901 ◽  
Author(s):  
Bruno Perillo ◽  
Annarita Sasso ◽  
Ciro Abbondanza ◽  
Giuseppe Palumbo
Keyword(s):  
Transcriptional Control ◽  
Mrna Level ◽  
Hormone Treatment ◽  
In Vitro Assays ◽  
Coding Region ◽  
Coding Sequence ◽  
17Β Estradiol ◽  
Responsive Element ◽  
Mcf 7

ABSTRACT We have found that 17β-estradiol induces bcl-2transcription in human breast cancer MCF-7 cells. To identifycis-acting elements involved in this regulation, we have analyzed hormone responsiveness of transiently transfected reporter constructs containing the bcl-2 major promoter (P1). Hormone inducibility was observed only when either of two sequences, located within the bcl-2 coding region and showing one and two mutations with respect to the consensus estrogen-responsive element, were inserted downstream from the P1 promoter. Both sequences behaved as enhancers exclusively in cells expressing the estrogen receptor and were able to bind this receptor in in vitro assays. Transfections into MCF-7 cells of plasmids carrying a bcl-2 cDNA fragment which included these two elements revealed that their simultaneous presence resulted in an additive effect on reporter gene activity, whose size resembled the increase of endogenous bcl-2 mRNA level observed in untransfected cells after hormone treatment. Moreover, the identified elements were able to mediate up-regulation ofbcl-2 expression by 17β-estradiol, since exogenousbcl-2 mRNA was induced by hormone challenge of MCF-7 cells transiently transfected with a vector containing the bcl-2coding sequence cloned under the control of a non-estrogen-responsive promoter. Finally, we show that hormone prevention of apoptosis, induced by incubating MCF-7 cells with hydrogen peroxide, was strictly related to bcl-2 up-regulation. Our results indicate that the bcl-2 major promoter does not containcis-acting elements directly involved in transcriptional control by 17β-estradiol and that hormone treatment inhibits programmed cell death in MCF-7 cells, inducing bcl-2expression via two estrogen-responsive elements located within its coding region.

Sign in / Sign up

Export Citation Format

Share Document