scholarly journals Estrogen Receptor β Isoforms Exhibit Differences in Ligand-Activated Transcriptional Activity in an Estrogen Response Element Sequence-Dependent Manner

Endocrinology ◽  
2004 ◽  
Vol 145 (1) ◽  
pp. 149-160 ◽  
Author(s):  
Timothy L. Ramsey ◽  
Kelly E. Risinger ◽  
Sarah C. Jernigan ◽  
Kathleen A. Mattingly ◽  
Carolyn M. Klinge
Keyword(s):  
Estrogen Receptor ◽  
Transcriptional Activity ◽  
Estrogen Receptor Β ◽  
Estrogen Response Element ◽  
Dependent Manner ◽  
Response Element ◽  
Sequence Dependent ◽  
Estrogen Response ◽  
Element Sequence

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 The Conundrum of Estrogen Receptor Oscillatory Activity in the Search for an Appropriate Hormone Replacement Therapy

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2256-2265 ◽  
Author(s):  
Sara Della Torre ◽  
Andrea Biserni ◽  
Gianpaolo Rando ◽  
Giuseppina Monteleone ◽  
Paolo Ciana ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Transcriptional Activity ◽  
Hormone Replacement ◽  
Oscillatory Activity ◽  
Luciferase Reporter ◽  
Specific Gene ◽  
Estrogen Response Element ◽  
Response Element ◽  
Tissue Specific ◽  
Estrogen Response

By the use of in vivo imaging, we investigated the dynamics of estrogen receptor (ER) activity in intact, ovariectomized, and hormone-replaced estrogen response element-luciferase reporter mice. The study revealed the existence of a long-paced, noncircadian oscillation of ER transcriptional activity. Among the ER-expressing organs, this oscillation was asynchronous and its amplitude and period were tissue dependent. Ovariectomy affected the amplitude but did not suppress ER oscillations, suggesting the presence of tissue endogenous oscillators. Long-term administration of raloxifene, bazedoxifene, combined estrogens alone or with basedoxifene to ovariectomized estrogen response element-luciferase mice showed that each treatment induced a distinct spatiotemporal profile of ER activity, demonstrating that the phasing of ER activity among tissues may be regulated by the chemical nature and the concentration of circulating estrogen. This points to the possibility of a hierarchical organization of the tissue-specific pacemakers. Conceivably, the rhythm of ER transcriptional activity translates locally into the activation of specific gene networks enabling ER to significantly change its physiological activity according to circulating estrogens. In reproductive and nonreproductive organs this hierarchical regulation may provide ER with the signaling plasticity necessary to drive the complex metabolic changes occurring at each female reproductive status. We propose that the tissue-specific oscillatory activity here described is an important component of ER signaling necessary for the full hormone action including the beneficial effects reported for nonreproductive organs. Thus, this mechanism needs to be taken in due consideration to develop novel, more efficacious, and safer hormone replacement therapies.

scholarly journals POU Transcription Factors Brn-3a and Brn-3b Interact with the Estrogen Receptor and Differentially Regulate Transcriptional Activity via an Estrogen Response Element

1998 ◽  
Vol 18 (2) ◽  
pp. 1029-1041 ◽  
Author(s):  
Vishwanie Budhram-Mahadeo ◽  
Malcolm Parker ◽  
David S. Latchman
Keyword(s):  
Estrogen Receptor ◽  
Transcription Factors ◽  
Transcriptional Activity ◽  
Inhibitory Effect ◽  
Single Amino Acid ◽  
Estrogen Response Element ◽  
Response Element ◽  
Pou Domain ◽  
Estrogen Response ◽  
Repressive Effect

ABSTRACT The estrogen receptor (ER) modulates transcription by forming complexes with other proteins and then binding to the estrogen response element (ERE). We have identified a novel interaction of this receptor with the POU transcription factors Brn-3a and Brn-3b which was independent of ligand binding. By pull-down assays and the yeast two-hybrid system, the POU domain of Brn-3a and Brn-3b was shown to interact with the DNA-binding domain of the ER. Brn-3–ER interactions also affect transcriptional activity of an ERE-containing promoter, such that in estradiol-stimulated cells, Brn-3b strongly activated the promoter via the ERE, while Brn-3a had a mild inhibitory effect. The POU domain of Brn-3b which interacts with the ER was sufficient to confer this activation potential, and the change of a single amino acid in the first helix of the POU homeodomain of Brn-3a to its equivalent in Brn-3b can change the mild repressive effect of Brn-3a to a stimulatory Brn-3b-like effect. These observations and their implications for transcriptional regulation by the ER are discussed.

scholarly journals Estrogen response element and the promoter context of the human and mouse lactoferrin genes influence estrogen receptor α-mediated transactivation activity in mammary gland cells

2004 ◽  
Vol 33 (2) ◽  
pp. 315-334 ◽  
Author(s):  
Kenya Stokes ◽  
Brenda Alston-Mills ◽  
Christina Teng
Keyword(s):  
Estrogen Receptor ◽  
Transcriptional Activity ◽  
Estrogen Receptor Α ◽  
Human Lactoferrin ◽  
Estrogen Response Element ◽  
Chimeric Mouse ◽  
Response Element ◽  
Estrogen Response ◽  
Lactoferrin Gene ◽  
Human And Mouse

A critical step in estrogen action is the recognition of estrogen responsive elements (EREs) by liganded estrogen receptor. Our current studies were designed to determine whether an extended estrogen response element half-site (ERRE) contributes to the differential estrogen responses of the human and mouse lactoferrin overlapping chicken ovalbumin upstream promoter/ERE sequences (estrogen response modules, ERMs) in the context of their natural promoters. Transient transfections of MCF-7 cells show that liganded estrogen receptor α (ERα) activates transcription of the human lactoferrin ERM fourfold higher than the mouse lactoferrin ERM in the context of their natural promoters. Since the ERRE of the human lactoferrin gene naturally occurs 18 bp upstream from the ERM and is absent in the mouse lactoferrin gene promoter, we created a chimeric mouse lactoferrin CAT reporter, which now encodes the ERRE in the identical location as in the human lactoferrin gene. The addition of the ERRE in the mouse lactoferrin gene rendered this reporter extremely responsive to estrogen stimulation. Using limited protease digestions and electrophoretic mobility shift assays, we showed that the binding and protease sensitivity of ERα bound to the mouse ERM with or without the ERRE, differed. Importantly, occupancy of additional nuclear receptors at the ERRE may contribute to ERα binding and activation. Furthermore, the presence of ERRE influences the selectivity of coactivators in liganded ERα-mediated transcriptional activity. When the receptor is bound to human and mouse plus genes, which contain the ERRE, steroid receptor coactivator (SRC)-2 was preferred, while SRC-1 and SRC-3 coactivators selectively enhanced the mouse lactoferrin gene activity. Moreover, peroxisome proliferator activated receptor-γ coactivator-1 (PGC-1α) and PGC-1-related estrogen receptor coactivator (PERC) robustly increase the transcriptional function of ERα in the presence of the ERRE. In conclusion, these data show that the context of the lactoferrin gene influences the ERα-mediated transcriptional activity.

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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