Binding of glucocorticoids to liver nuclei and chromatin of fetal, immature and adult rats.
The interaction of dexamethasone with nuclei and chromatin was investigated following incubation of liver slices from fetal, immature (6-day-old) and adult rats with the labeled steroid at 37 degrees. The number of specific binding sites for dexamethasone in purified liver nuclei increases with the age of the animal in a manner similar to that previously reported for the cytoplasmic receptor. The high affinity nuclear binding approaches saturation at 40 and 500 nM dexamethasone in fetal and adult liver, respectively. In comparison with dexamethasone, the relative efficiency of corticosterone to accumulate in the nucleus is 9 percent in fetal liver and only 1 percent in adult liver. Specifically bound dexamethasone in adult nuclei exists in at least three forms; a Tris-soluble, a KC1-soluble, and a residual (non-extractable with KC1 or DNase) form. Part of the Tris-soluble steroid is associated with macromolecules sedimenting at about 4 S both in the presence and absence of 0.4 M KC1. This form of the receptor was not detected in fetal liver nuclei. In liver chromatin, bound dexamethasone exists in a KC1-soluble and a residual form, the latter comprising the major fraction of steroid associated with chromatin from both fetal and adult tissue (60 and 75 percent, respectively). Treatment with Triton X-100 releases about 20 percent of the radioactivity in adult liver nuclei, but has no effect on fetal liver nuclei. In contrast with the above observations in the intact tissue, the major fraction of steroid bound to chromatin in cell-free systems is KC1- and DNase-soluble, only 30 percent remaining in the residual pellet.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003851:Deoxyribonucleases; D003907:Dexamethasone / Q000378:metabolism*; D005333:Fetus; D006854:Hydrocortisone / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000254:growth & development / Q000378:metabolism*; D009994:Osmolar Concentration; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000302:isolation & purification / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*
D002843:Chromatin; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D011189:Potassium Chloride; D003907:Dexamethasone; D003851:Deoxyribonucleases; D003345:Corticosterone; D006854:Hydrocortisone