Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors α and β

Kuiper, George G. J. M.; Carlsson, Bo; Grandien, Kaj; Enmark, Eva; Häggblad, Johan; Nilsson, Stefan; Gustafsson, Jan Åke

doi:10.1210/endo.138.3.4979

Cited by 3,177 publications

(825 citation statements)

References 36 publications

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“…Previous studies have indicated that the iso¯avonoid genistein shows a higher a nity for ERb (Barkhem et al, 1998;Kuiper et al, 1997). 293 cells were cotransfected as before with the ERE-reporter plasmid and ERa or ERb expressing plasmids and treated with increasing amounts of genistein.…”

Section: Erb Promotes the Agonistic Effect Of Genisteinmentioning

confidence: 99%

Estrogen receptor β acts as a dominant regulator of estrogen signaling

2000

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The physiological e ects of estrogens are mediated by two intracellular transcription factors, the estrogen receptors (ERs), that regulate transcription of target genes through binding to speci®c DNA target sequences. Here we describe alterations in cellular responses to di erent ER agonists and to the anti-estrogenic compound tamoxifen resulting from co-expression of the two ERs in transient co-transfection experiments. Our results demonstrate that ERb can act as a negative or positive dominant regulator of ER activity. This is manifested through reduced transcriptional activity at low concentrations of estradiol (E 2 ); increased antagonistic e ects of tamoxifen on E 2 stimulated activity; and enhanced agonistic action of the phytoestrogenic compound genistein. Furthermore, using chimeric proteins lacking the N-terminal activation function 1 (AF-1), we show that the di erential responses of ERa and ERb to di erent agonists and antagonists are primarily dictated by inherent di erences in the C-terminal ligand-binding domains of the receptors, whereas the magnitude of transcriptional activity is in¯uenced by ERa AF-1, but not ERb AF-1. The ERa AF-1 activity appears to be modulated upon co-expression of both ERs. The alterations in transcriptional activity resulting from co-expression of ERa and ERb are probably due to the formation of a/b heterodimeric complexes. This study demonstrates that co-localization and subsequent heterodimerization of ERa and ERb may result in receptor activity distinct from that of ER homodimers.

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Section: Erb Promotes the Agonistic Effect Of Genisteinmentioning

confidence: 99%

Estrogen receptor β acts as a dominant regulator of estrogen signaling

2000

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“…In a cell culture assay, amphioxus SR is not as responsive to E2 as is human ERα; the SR requires about 100 nM E2 to activate gene transcription to 50% of the maximum response [13]. This is substantially higher than 0.2 nM E2 for the Kd of E2 for human ERα [15].…”

Section: Discussionmentioning

confidence: 92%

“…A surprising finding is that amphioxus ER does not bind steroids [13,14]. In contrast, amphioxus SR is activated by estradiol [13], although at an estradiol concentration that is more than 100-fold higher than found for binding to human ERα [15]. Unexpectedly, the SR does not bind 3-ketosteroids [13], despite the clear phylogenetic clustering of the SR with the GR, MR, PR and AR [13,14].…”

mentioning

confidence: 91%

3D model of amphioxus steroid receptor complexed with estradiol

Baker

Chang

2009

Biochemical and Biophysical Research Communications

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“…Thus, estrogen attenuates the antidiuretic effect of VP. This may reflect activation of ERα, because although both ERα and ERβ have been localized to the kidney [100], ERα is most prominent [33] (See Table 2). ERα is present in the collecting duct in rat kidney [100], the antidiuretic site of VP, and estrogen regulation of gene expression is dependent on ERα in the kidney [30].…”

Section: Effects On Vp-induced Antidiuresismentioning

confidence: 99%

Estrogen receptors: Their roles in regulation of vasopressin release for maintenance of fluid and electrolyte homeostasis

Sladek

Somponpun

2008

Frontiers in Neuroendocrinology

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Long standing interest in the impact of gonadal steroid hormones on fluid and electrolyte balance has led to a body of literature filled with conflicting reports about gender differences, the effects of gonadectomy, hormone replacement, and reproductive cycles on plasma vasopressin (VP), VP secretion, and VP gene expression. This reflects the complexity of gonadal steroid hormone actions in the body resulting from multiple sites of action that impact fluid and electrolyte balance (e.g. VP target organs, afferent pathways regulating the VP neurons, and the VP secreting neurons themselves). It also reflects involvement of multiple types of estrogen receptors (ER) in these diverse sites including ERs that act as transcription factors regulating gene expression (i.e. the classic ERα as well as the more recently discovered ERβ) and potentially G-protein coupled, membrane localized ERs that mediate rapid non-genomic actions of estrogen. Furthermore, altered expression of these receptors in physiologically diverse conditions of fluid and electrolyte balance contributes to the difficulty of using simplistic approaches such as gender comparisons, gonadectomy, and hormone replacement to assess the role of gonadal steroids in regulation of VP secretion for maintenance of fluid and electrolyte homeostasis. This review catalogs these inconsistencies and provides a frame work for understanding them by describing: 1) the effect of gonadal steroids on target organ responsiveness to VP; 2) the expression of multiple types of estrogen receptors in the VP neurons and in brain regions monitoring feedback signals from the periphery; and 3) the impact of dehydration and hyponatremia on expression of these receptors.

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Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors α and β

Cited by 3,177 publications

References 36 publications

Estrogen receptor β acts as a dominant regulator of estrogen signaling

Estrogen receptor β acts as a dominant regulator of estrogen signaling

3D model of amphioxus steroid receptor complexed with estradiol

Estrogen receptors: Their roles in regulation of vasopressin release for maintenance of fluid and electrolyte homeostasis

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