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- Title
Corticoids and Human Skin Fibroblasts: Intracellular Specific Binding in Relation to Growth Inhibition.
- Authors
Ponec, Maria; de Kloet, E. Ronald; Kempenaar, Johanna A.
- Abstract
The binding of ³H-triamcinolone acetonide to soluble macromolecules of cultured human skin fibroblasts was studied in an attempt to explain the mechanism underlying the inhibitory effects of glucocorticoids on cell growth. The results were as follows: Cultured human skin fibroblasts contain in cytosol a high affinity binding system for glucocorticoids. Various glucocorticoid derivatives competed for specific binding of ³H-triamcinolone acetonide. In some but not all instances this competition was related to the clinical efficacy of the derivatives under study and to their potency for the inhibition of cell growth. A specific glucocorticoid binding system was detectable in steroid-sensitive, low-density cell cultures (apparent Bmax = 200 fmoles/mg protein). The number of steroid binding sites was lower in high-density cell cultures (apparent Bmax = 125 fmoles/mg protein). The sensitivity to growth inhibition by glucocorticoids was markedly decreased in the high-density cell cultures. There were no differences in the affinity constants between these cell cultures (Kdiss = 3.3 × 10-9 M). When cells were grown in medium containing glucocorticoid, renewal of the incubation medium led to disappearance of the growth-inhibitory effects, whereas specific binding was not affected. Nandrolone, an inhibitor of cell growth, abolished the growth-inhibitory effects of glucocorticoids but did not displace ³H-triamcinolone acetonide from its binding sites. The results suggest that in addition to a mechanism mediated by a glucocorticoid binding system with receptor like properties also other factors as well appear of relevance for the control of cell growth. These factors may be beyond the actual binding process of steroid and involve the action at the level of genomic expression of the cell.
- Subjects
FIBROBLASTS; GLUCOCORTICOIDS; GROWTH factors; CELL culture; STEROIDS; GENE expression
- Publication
Journal of Investigative Dermatology, 1980, Vol 75, Issue 4, p293
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12530810