Estrogen response element-independent regulation of gene expression by genistein in intestinal cells

2003 ◽  
Vol 1627 (2-3) ◽  
pp. 63-70 ◽  
Author(s):  
Ping Hua ◽  
Wan-Jung Tsai ◽  
Shiu-Ming Kuo
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Intestinal Cells ◽  
Estrogen Response Element ◽  
Response Element ◽  
Estrogen Response

scholarly journals Cross Talk in Hormonally Regulated Gene Transcription through Induction of Estrogen Receptor Ubiquitylation

2005 ◽  
Vol 25 (16) ◽  
pp. 7386-7398 ◽  
Author(s):  
Min Luo ◽  
Mingshi Koh ◽  
Jiajun Feng ◽  
Qiang Wu ◽  
Philippa Melamed
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Cross Talk ◽  
Estrogen Receptor Alpha ◽  
Regulation Of Gene Expression ◽  
Gonadotropin Releasing Hormone ◽  
Estrogen Response Element ◽  
Estrogen Response ◽  
New Form ◽  
Cycling Time

ABSTRACT Estrogen tightly regulates the levels of circulating gonadotropins, but a direct effect of estrogen receptor alpha (ERα) on the mammalian LHβ gene has remained poorly defined. We demonstrate here that ERα can associate with the LHβ promoter through interactions with Sf-1 and Pitx1 without requiring an estrogen response element (ERE). We show that gonadotropin-releasing hormone (GnRH) promotes ERα ubiquitylation and also degradation while stimulating expression of ubc4. GnRH also increases the association and lengthens the cycling time of ERα on the LHβ promoter. The ERα association and transactivation of the LHβ gene, as well as ERα degradation, are increased following ubc4 overexpression, while the effects of GnRH are abated following ubc4 knockdown. Our results indicate that ERα ubiquitylation and subsequent transactivation of the LHβ gene can be induced by increasing the levels of the E2 enzyme as a result of signaling by an extracellular hormone, thus providing a new form of cross talk in hormonally stimulated regulation of gene expression.

scholarly journals Examination of ERα Signaling Pathways in Bone of Mutant Mouse Models Reveals the Importance of ERE-Dependent Signaling

Endocrinology ◽  
2012 ◽  
Vol 153 (11) ◽  
pp. 5325-5333 ◽  
Author(s):  
Kumar Chokalingam ◽  
Matthew M. Roforth ◽  
Kristy M. Nicks ◽  
Ulrike McGregor ◽  
Daniel Fraser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Models ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Specific Gene ◽  
Estrogen Response Element ◽  
Response Element ◽  
Estrogen Response ◽  
Extracellular Matrix Interactions ◽  
Bone Physiology

Abstract The mechanisms of estrogen receptor (ER)-α activity can be categorized into those involving direct (classical) or indirect (nonclassical) DNA binding. Although various mouse models have demonstrated the importance of ERα in bone, the specific gene expression patterns affected by these modes of ERα action are unknown. In this report, the gene expression patterns of ERα-deficient (ERKO) mice and nonclassical ER knock-in (NERKI) mice, which can function only by nonclassical means, were analyzed. Three-month-old mice were ovariectomized and implanted with estrogen pellets for 1 month to normalize estrogen levels. Microarray analysis of flushed cortical bone revealed 28% (210 of 763) of the genes differentially expressed in ERKO mice were altered in NERKI mice, suggesting estrogen response element-dependent regulation of these genes in bone. Pathway analysis revealed alterations in genes involved in focal adhesion and extracellular matrix interactions. However, the majority of genes regulated in ERKO mice (72%) were unique (i.e. not altered in NERKI mice), suggesting these are regulated by nonclassical mechanisms. To further explore the pathways affected in ERKO mice, we performed focused quantitative PCR arrays for genes involved in various aspects of bone physiology. Genes involved in bone formation, senescence, apoptosis, and autophagy were significantly regulated. Overall, the majority of the genes regulated by ERα in bone are via nonclassical pathways. However, because NERKI mice display an osteoporotic phenotype, it can be deduced that the minority of the estrogen response element-dependent genes/pathways play critical roles in the regulation of bone physiology. These data demonstrate the importance of classical ERα signaling in regulating bone metabolism.

scholarly journals A Functional Serine 118 Phosphorylation Site in Estrogen Receptor-α Is Required for Down-Regulation of Gene Expression by 17β-Estradiol and 4-Hydroxytamoxifen

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4634-4641 ◽  
Author(s):  
Jingwei Cheng ◽  
Chen Zhang ◽  
David J. Shapiro
Keyword(s):  
Estrogen Receptor ◽  
Regulation Of Gene Expression ◽  
Phosphorylation Site ◽  
Estrogen Receptor Α ◽  
Estrogen Response Element ◽  
Down Regulation ◽  
Response Element ◽  
Estrogen Response ◽  
Endogenous Genes ◽  
17Β Estradiol

To evaluate the contribution of ERK1/2 phosphorylation of estrogen receptor (ER)-α to activation and repression of endogenous genes, we produced stably transfected lines of HeLa cells with functional ERK1/2 pathways that express similar levels of wild-type human ERα and ERα mutated to inactivate the well-known MAPK site at serine 118 (ERαS118A). We compared effects of the S118A mutation on 17β-estradiol (E2)-mediated transactivation, which is heavily dependent on activation function (AF) 2 of ERα and on 4-hydroxytamoxifen (OHT)-mediated transactivation, which is heavily dependent on AF1, which includes S118. To examine whether S118 was the key ERK/MAPK phosphorylation site in ERα action, we compared the effects of the S118A mutant and the ERK inhibitor U0126 on expression of endogenous genes. In several estrogen response element-containing genes, the S118A mutation strongly reduced induction by E2, and U0126 did not further reduce expression. Expression of another group of estrogen response element-containing genes was largely unaffected by the S118A mutation. The S118A mutation had variable effects on genes induced by ER tethering or binding near specificity protein-1 and activator protein-1 sites. For five mRNAs whose expression is strongly down-regulated by E2 and partially or completely down-regulated by OHT, the S118A mutation reduced or abolished down-regulation by E2 and nearly abolished down-regulation by OHT. In contrast, for Sma and mothers against decapentaplegic-3-related, which is down-regulated by E2 and not OHT, the S118A mutation had little effect. These data suggest that there may be distinct groups of genes down-regulated by ERα and suggest a novel role for ERK phosphorylation at serine 118 in AF1 in regulating expression of the set of genes down-regulated by OHT.

Genistein increases metallothionein expression in human intestinal cells, Caco-2

1999 ◽  
Vol 77 (2) ◽  
pp. 79-88 ◽  
Author(s):  
Shiu-Ming Kuo ◽  
Penny S Leavitt
Keyword(s):  
Gene Expression ◽  
Metal Binding ◽  
Steroid Hormone ◽  
Antioxidant Property ◽  
Intestinal Cells ◽  
Estrogen Response Element ◽  
Mrna Levels ◽  
Estrogen Response ◽  
Dose Dependent ◽  
Human Intestinal Cells

Flavonoids found in common vegetables, fruits, and legumes have been shown to possess antioxidant property. This study is the first to demonstrate that one member of the flavonoid family, genistein, can induce the expression of metallothionein (a metal-binding protein with antioxidant property). We found the effect of genistein to be time- and dose-dependent (10-100 µM). The effect can be observed at both protein and mRNA levels and was synergistic to that of 30 µM zinc. Genistein was shown previously to interact with the estrogen receptor and induce gene expression similar to estrogens at a lower affinity. We thus tested the hypothesis that the effect of genistein on metallothionein expression was mediated through the steroid hormone pathway. We found that various glucocorticoids do not affect metallothionein expression in Caco-2 cells. 17beta-estradiol at 10-100 µM (concentrations much higher than needed to activate the estrogen response element) induced metallothionein expression in Caco-2 cells. However, a synthetic estrogen, diethylstilbestrol, did not increase metallothionein level at 10 µM. 17beta-Estradiol also did not act synergistically with zinc. Thus, genistein may enhance metallothionein expression through an uncharacterized mechanism. Further studies are needed to delineate the molecular mechanism and to determine whether the expression of other genes is also affected by genistein.Key words: metallothionein gene expression, genistein, flavonoid, estrogen, intestine.

scholarly journals Mouse Estrogen Receptor β Forms Estrogen Response Element-Binding Heterodimers with Estrogen Receptor α

1997 ◽  
Vol 11 (10) ◽  
pp. 1486-1496 ◽  
Author(s):  
Katarina Pettersson ◽  
Kaj Grandien ◽  
George G. J. M. Kuiper ◽  
Jan-Åke Gustafsson
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Estrogen Receptor Β ◽  
Estrogen Response Element ◽  
Response Element ◽  
Estrogen Response

scholarly journals Aromatase: Contributions to Physiology and Disease in Women and Men

Physiology ◽  
2016 ◽  
Vol 31 (4) ◽  
pp. 258-269 ◽  
Author(s):  
Jennifer Blakemore ◽  
Fredrick Naftolin
Keyword(s):  
Human Physiology ◽  
Estrogen Receptor ◽  
Aromatase Inhibitors ◽  
Reproductive System ◽  
Short Review ◽  
Estrogen Response Element ◽  
Comprehensive Overview ◽  
Response Element ◽  
Estrogen Response ◽  
Health And Disease

Aromatase (estrogen synthetase; EC 1.14.14.1) catalyzes the demethylation of androgens' carbon 19, producing phenolic 18-carbon estrogens. Aromatase is most widely known for its roles in reproduction and reproductive system diseases, and as a target for inhibitor therapy in estrogen-sensitive diseases including cancer, endometriosis, and leiomyoma (141, 143). However, all tissues contain estrogen receptor-expressing cells, the majority of genes have a complete or partial estrogen response element that regulates their expression (61), and there are plentiful nonreceptor effects of estrogens (79); therefore, the effect of aromatase through the provision of estrogen is almost universal in terms of health and disease. This review will provide a brief but comprehensive overview of the enzyme, its role in steroidogenesis, the problems that arise with its functional mutations and mishaps, the roles in human physiology of aromatase and its product estrogens, its current clinical roles, and the effects of aromatase inhibitors. While much of the story is that of the consequences of the formation of its product estrogens, we also will address alternative enzymatic roles of aromatase as a demethylase or nonenzymatic actions of this versatile molecule. Although this short review is meant to be thorough, it is by no means exhaustive; rather, it is meant to reflect the cutting-edge, exciting properties and possibilities of this ancient enzyme and its products.

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