Interaction of glucocorticoid · receptor complexes with rat liver nuclei |
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Authors: | Michel Atger Edwin Milgrom |
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Institution: | Groupe de Recherches sur la Biochimie Endocrinienne et la Reproduction (INSERM U 135), Faculté de Médecine Paris Sud, 94 Bicêtre, France |
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Abstract: | Some previous reports on acellular binding of glucocorticoid · receptor complexes to rat liver nuclei have pointed to the conclusion that there exists a small number of high affinity nuclear “receptor” sites. Various investigations lead us to the opposite conclusion and suggest that these results were actually due to the presence, in the cytosol, of one or several macromolecules which inhibited the binding to nuclei of steroid · receptor complexes. The mechanism of this inhibition was examined. It appeared to be due not to a competition between both molecules for the same nuclear acceptor site but to an interaction in the cytosol between teh inhibitor and the steroid · receptor complex which prevented the binding of the latter to the nuclei. The search for high affinity specific acceptor sites was also negative for physiological saline conditions and for the non-salt-extractable fraction of the nuclear receptor. When 940-fold purified receptor · steroid complexes were used, very high concentrations of complexes could be achieved and saturation of nuclei was then observed, but only under physiological ionic strength conditions. However, the interaction was of relatively low affinity (KA = 3.8 · 107 M?1) and to a great number of acceptor sites (N = 26.2 pmol/mg DNA), largely exceeding the cellular concentration of receptor (5.8 pmol/mg DNA).These results suggested that saturation of nuclei by steroid · receptor complexes should not occur in the intact liver cell. They were confirmed by studies on the distribution of steroid · receptor complexes in liver slices incubated with various concentrations of 3H]dexamethasone. For all hormone concentrations a constant proportion (90%) of the complexes was found in the nuclei, thus showing no saturation of the nuclear acceptor sites. |
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Keywords: | dexamethasone 9-α-fluro 11-β 17 21-trihydroxy-16α-methyl pregna-1 4diene-3 20-dione triamcinolone 9α-fluoro-11β 16α 17 21-tetrahydroxy-pregna-1 4-diene-3 20-dione |
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