Linked Life Data

17509631

Source:http://linkedlifedata.com/resource/pubmed/id/17509631

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6-7
pubmed:dateCreated
2007-5-25
pubmed:abstractText
Mifepristone is an antagonist of the glucocorticoid receptor (GR) that also has significant agonist activity in some cell types. We examined the partial agonist activity of mifepristone in COS-7 cells transfected with increasing amounts of a glucocorticoid receptor expression vector pmGR. As pmGR levels increased, the response of the reporter, pMTVCAT to dexamethasone increased, consistent with increasing levels of receptor expression; the response to mifepristone also increased but at a higher rate, resulting in increasing mifepristone agonist and decreasing antagonist activity. In contrast, increasing pMTVCAT levels increased CAT activity induced by both dexamethasone and mifepristone, but did not change the relative agonist activity of mifepristone. We also examined the relationship between agonist activity and receptor level in a series of clones of the E8.2.A3 cell line expressing various levels of GR. Again, the relative agonist activity of mifepristone increased as GR increased. This increase was not due to changes in the dose response curves to these two ligands since their EC50 values were independent of receptor levels. These results indicate that the degree of glucocorticoid agonist activity exhibited by mifepristone is dependent on the concentration of GR in the cell. Similar results were obtained with another partial agonist of the GR, progesterone, whereas the complete antagonist ZK98.299 had no agonist activity under any condition. Taken together, these results suggest that the phenomenon of receptor concentration-dependence is a property of partial GR agonists in general.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0039-128X
pubmed:author
pubmed:issnType
Print
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
600-8
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The glucocorticoid agonist activities of mifepristone (RU486) and progesterone are dependent on glucocorticoid receptor levels but not on EC50 values.
pubmed:affiliation
Division of Molecular Pathobiology, Department of Environmental and Infectious Disease Sciences, American Registry of Pathology, Armed Forces Institute of Pathology, Washington, DC 20306, USA. zhangs@afip.osd.mil
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural