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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1985-2-15
|
| pubmed:abstractText |
Glucocorticoid-receptor activation in GH1 cells results from the conversion of a 10 S oligomeric cytosolic form to a 4-5 S nuclear-binding species (Raaka, B. M., and Samuels, H. H. (1983) J. Biol. Chem. 258, 417-425). In this study, we report that triamcinolone acetonide (9 alpha-fluoro-11 beta, 16 alpha, 17 alpha, 21-tetrahydroxypregna-1,4-diene-3,20-dione 16,17-acetonide) elicits a time- and dose-dependent reduction of total-cell (nuclear + cytoplasmic) receptor. The mechanism of receptor regulation was studied by dense amino acid labeling of receptor using media containing 2H, 13C, and 15N-labeled amino acids. Total cell receptor was extracted with 0.4 M KCl and newly synthesized dense receptor was separated from pre-existing receptor of normal density by centrifugation in gradients of 15-30% sucrose (w/v) in D2O. Receptor levels in cells grown without [3H]triamcinolone acetonide was 260 +/- 19 fmol/100 micrograms of DNA (16,000 molecules/cell), and, with 10 nM [3H]triamcinolone acetonide, this decreased to 130 +/- 14 fmol/100 micrograms of DNA after 30 h. Receptor half-life was 19 +/- 1.9 h in the absence and 9.5 +/- 0.3 h in the presence of triamcinolone acetonide and accounted for the decrease in steady-state receptor levels. Receptor synthesis was 9.7 +/- 0.3 fmol/100 micrograms of DNA/h (580 molecules/cell/h) both in the presence and absence of 10 nM [3H]triamcinolone acetonide. Triamcinolone acetonide reduced the half-life in proportion to the extent of receptor occupancy and activation. During the approach to steady-state conditions, 10 nM [3H]triamcinolone acetonide shortened receptor half-life almost immediately to the value in cells grown with [3H]triamcinolone acetonide for 24 h or longer. Cycloheximide did not prevent the triamcinolone acetonide-mediated decrease in receptor half-life and the shortening of receptor half-life is rapidly reversed by removal of hormone. These studies support a model of receptor regulation in which triamcinolone acetonide converts the unactivated 10 S receptor to the activated 4-5 S form which is degraded at an increased rate by the cell.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
10
|
| pubmed:volume |
260
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
418-27
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:3965455-Animals,
pubmed-meshheading:3965455-Cell Line,
pubmed-meshheading:3965455-Cell Nucleus,
pubmed-meshheading:3965455-Centrifugation, Density Gradient,
pubmed-meshheading:3965455-Cycloheximide,
pubmed-meshheading:3965455-Half-Life,
pubmed-meshheading:3965455-Kinetics,
pubmed-meshheading:3965455-Liver Neoplasms, Experimental,
pubmed-meshheading:3965455-Pituitary Neoplasms,
pubmed-meshheading:3965455-Rats,
pubmed-meshheading:3965455-Receptors, Glucocorticoid,
pubmed-meshheading:3965455-Receptors, Steroid,
pubmed-meshheading:3965455-Triamcinolone Acetonide
|
| pubmed:year |
1985
|
| pubmed:articleTitle |
Triamcinolone acetonide regulates glucocorticoid-receptor levels by decreasing the half-life of the activated nuclear-receptor form.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|