Interaction of glucocorticoid analogues with the human glucocorticoid receptor.
Transient co-transfection of receptor cDNA and suitable reporter genes was used to study human glucocorticoid receptor (hGR) function in a neutral mammalian cell background. A variety of natural and synthetic steroids were analyzed for their ability to activate gene expression through the hGR and to bind to extracts of cells expressing the hGR cDNA. There was very good correlation between these two in vitro parameters for these compounds. Furthermore, correlation of these data with reported in vivo anti-inflammatory potencies was surprisingly close, with two exceptions. The in vitro data suggest an explanation for the discrepant compounds, consistent with published data on their metabolic fate in vivo. The co-transfection assay has utility as a quantitative predictor of in vivo glucocorticoid pharmacology.
Berger
T S
TS
Ligand Pharmaceuticals Inc., San Diego, CA 92121.
Parandoosh
Z
Z
Perry
B W
BW
Stein
R B
RB
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation; D014162:Transfection
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D004247:DNA