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Human Estrogen Receptor (human + estrogen_receptor)
Selected AbstractsInteraction of stilbene compounds with human and rainbow trout estrogen receptorsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2008Denina Bobbie Dawn Simmons Abstract Compounds with stilbene structures are widely used as pharmaceuticals and personal care products (PPCPs) and are present in plants. A suite of stilbene-related compounds, including PPCPs and plant-derived compounds were tested in vitro for interactions with the human and rainbow trout estrogen receptors and in vivo with rainbow trout using vitellogenin levels as a biomarker. Among the compounds with antagonistic activity, the common structural similarity was (in addition to the stilbene backbone) the presence of 4-hydroxy substitution. Stilbene-related compounds found to act as inhibitors at the estrogen receptor included the plant-derived compound resveratrol and two formulations of fluorescent whitening agents used in detergents, 4,4,-bis(2-sulfostyryl)biphenyl and diaminostilbene-1. In the yeast estrogenicity screening assay, the concentrations which caused a 50% inhibition in estrogenic response (IC50s) with the human estrogen receptor ranged from 2.56 × 10,6 to 2.56 × 10,6 M. In the rainbow trout estrogen receptor assay, the IC50s ranged from 7.75 × 10,8 to 1.11 × 10,5 M. However, in the in vivo rainbow trout vitellogenin assay, tamoxifen was the only stilbene of the compounds tested to have a significant effect as an inhibitor of estrogenicity. [source] Impact of activated sludge-derived colloidal organic carbon on behavior of estrogenic agonist recombinant yeast bioassayENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2005R. David Holbrook Abstract The impact of size-fractionated colloidal organic carbon (COC) originating from a biological wastewater treatment facility on the sensitivity of the yeast estrogen screen (YES) bioassay containing the human estrogen receptor (hER) gene was evaluated. Dose-response curves of serially diluted 17,-estradiol (E2), both in the presence and absence of COC, were generated by the YES bioassay. The concentration of E2 leading to a 50% YES response (effective concentration 50%, or EC50) was used to evaluate quantitatively the estrogenic activity of the different COC-E2 mixtures. The EC50 values for all COC size fractions, including COC-free samples (<1 kD), were statistically greater than the controls using Milli-Q water. Normalized EC50 values significantly increased as a function of COC concentration for the larger size fractions (>0.22 ,m), but were not significantly affected by smaller COC material at environmental levels (1,5 mg/L), while both colloidal polysaccharide concentrations and colloidal fluorophores (measured at an excitation/emission wavelength pair of 350 nm/450 nm) appear to have an important role in the sensitivity of the YES bioassay. Estimates of the colloid-associated E2 fraction did not predict accurately increases in EC50 values. Matrix effects of the specific environment being tested with the YES bioassay need to be evaluated closely due to the sensitivity of the hER and reporter plasmid. [source] Estrogenicity in bile of juvenile rainbow trout as measure of exposure and potential effects of endocrine disruptorsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2004Ann-Sofie Allard Abstract Estrogenicity in the bile of juvenile rainbow trout exposed to effluents from municipal sewage treatment plants and various industries was assayed by using a recombinant yeast strain containing the human estrogen receptor , gene. Estrogenicity in bile also was measured after deconjugation of steroids to provide an estimate of the exposure and as an endpoint for potential effects on the organism. In unexposed fish or fish exposed for three weeks at control localities, 0.5 to 9 ng of estradiol equivalents (EEq) were found per gram of bile (ng EEq/g bile). Fish exposed for three weeks in cages placed in the receiving waters near outlets of municipal effluent had an average activity of 26 ng EEq/g bile. Fish exposed to undiluted sewage water in aquaria had a bile estrogenicity of 51 to 87,000 ng EEq/g bile. Unconjugated estrogens contributed only 8% or less to the estrogenicity in bile of fish exposed to municipal effluents. Municipal sewage effluents were more estrogenic than the industrial effluents that were investigated. Estrogenicity in bile was compared to that in extracts of wastewater by using the same receptor assay, and to vitellogenin induction in the plasma of the same fish. Bile estrogenicity proved to be a useful and sensitive (internal) measure of exposure and indicated its potential for the display of biological effects as a complement or replacement of more laborious assays. [source] Repressive domain of unliganded human estrogen receptor , associates with Hsc70GENES TO CELLS, Issue 12 2005Satoko Ogawa Estrogen receptor (ER) is a hormone-inducible transcription factor as a member of the nuclear receptor gene superfamily. Unliganded ER is transcriptionally silent and capable of DNA binding; however, it is unable to suppress the basal activity of the target gene promoters, unlike non-steroid hormone receptors that associate with corepressors in the absence of their cognate ligands. To study the molecular basis of how unliganded human ER, is maintained silent in gene regulation upon the target gene promoters, we biochemically searched interactants for hER,, and identified heat shock protein 70 (Hsc70). Hsc70 appeared to associate with the N-terminal hormone binding E domain, that also turned out a transcriptionally repressive domain. Competitive association of Hsc70 with a best known coactivator p300 was observed. Thus, these findings suggest that Hsc70 associates with unliganded hER,, and thereby deters hER, from recruiting transcriptional coregulators, presumably as a component of chaperone complexes. [source] Identification of a human estrogen receptor ,-derived antiestrogenic peptide that adopts a polyproline II conformationJOURNAL OF PEPTIDE SCIENCE, Issue 7 2009Josef Kapitán Abstract Polyproline II (PPII) helix is an extended secondary structure present in a number of proteins. PPII-containing sequences mediate specific protein,protein interactions with partners containing appropriate cognate domains called PPII-recognizing domains (PRDs) and are involved in the activation of intracellular signaling pathways. Thus, the identification of PPII structures in proteins is of great interest, not only to explore molecular and physiological mechanisms, but also to elaborate new potential drugs. By revisiting X-ray crystal structures of liganded ,-type human estrogen receptor (ER,), we have identified an 11-residue PPII-helical sequence (D321AEPPILYSEY331) in the ligand-binding domain of the receptor. The data recorded by far-ultraviolet circular dichroism (far-UV CD), vibrational Raman optical activity (ROA) and differential scanning calorimetry (DSC) show that the corresponding peptide (Ac-DAEPPILYSEY-NH2) is particularly well structured in PPII, with the same proportion of PPII as observed from X-ray structures (,85%). In addition, studies carried out on ER,-negative Evsa-T breast cancer cells transiently co-transfected with a pcDNA3-ER, plasmid and a Vit-tk-Luc reporter gene revealed that the peptide antagonizes the estradiol-induced transcription providing perspectives for researching new molecules with antagonistic properties. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. [source] Estrogenic activity of Nigella damascena extracts, evaluated using a recombinant yeast screenPHYTOTHERAPY RESEARCH, Issue 5 2002E. Agradi Abstract We used the yeast estrogen screen (YES) containing a human estrogen receptor to evaluate the estrogenic activity of extracts obtained from Nigella damascena seeds. Alcohol extracts obtained by direct extraction of seeds showed a low estrogenic activity, while the alcohol extract obtained after extraction with solvents of increasing polarity showed a strong estrogenic activity. This suggests the presence in Nigella of polar components whose activity can be clearly demonstrated after previous elimination of interacting apolar components that may mask the activity of more polar components. The response of both alcohol fractions follow a bell-shaped curve indicating a concentration-dependent relationship. Copyright © 2002 John Wiley & Sons, Ltd. [source] | ||||||||||