Linked Life Data

9927308

Source:http://linkedlifedata.com/resource/pubmed/id/9927308

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-2-23
pubmed:abstractText
We report on the identification of novel, nonsteroidal ligands that show pronounced subtype-selective differences in ligand binding and transcriptional potency or efficacy for the two estrogen receptor (ER) subtypes, ER alpha and ER beta. An aryl-substituted pyrazole is an ER alpha potency-selective agonist, showing higher binding affinity for ER alpha and 120-fold higher potency in stimulation of ER alpha vs. ER beta in transactivation assays in cells. A tetrahydrochrysene (THC) has a 4-fold preferential binding affinity for ER beta; it is an agonist on ER alpha, but a complete antagonist on ER beta. Intriguingly, the antagonist activity of THC is associated with the R,R-enantiomer (R,R-THC). The S,S-enantiomer (S,S-THC) is an agonist on both ER alpha and ER beta but has a 20-fold lower affinity for ER beta than R,R-THC. This difference in binding affinity accounts for the full ER beta antagonist activity of the THC racemate (a 1:1 mixture of R,R-THC and S,S-THC). These compounds should be useful in probing the conformational changes in these two ERs that are evoked by agonists and antagonists, and in evaluating the distinct roles that ER beta and ER alpha may play in the diverse target tissues in which estrogens act.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
140
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
800-4
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Novel ligands that function as selective estrogens or antiestrogens for estrogen receptor-alpha or estrogen receptor-beta.
pubmed:affiliation
Department of Molecular and Integrative Physiology, University of Illinois, Urbana 61801-3704, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.