Interaction of Glucocorticoids with Rat Liver Nuclei: Effect of Adrenalectomy and Cortisol Administration

Abstract

Fifteen minutes after intraperi-toneal injection of [3H] dexamethasone, 20% of the radioactivity accumulates in the liver, where unrnetabolized dexamethasone can be found bound o t soluble proteins of the cytoplasm and the nucleus. The subcellular distribution of dexa-methasone radioactivity in the liver resembles that previously observed after injection of [3H] cortisol (1). Purified liver nuclei from intact male rats are able to bind [3H]dexamethasone in vitro. The process is temperature dependent and shows steroid and tissue specificities. The concentration of Mg2* and the presence of free sulfhydryl groups are essential for the binding reaction. Following adrenalectomy, whereas the total number of dexamethasone binding sites in the hepatocyte is unaltered, their concentration in the cytosol increases, and the nucleus progressively looses its capacity to incorporate [3H] dexametha-sone in vitro. Thirty minutes after injection of cortisol to adrenalectomized rats the concentration of the dexamethasone binding protein in the cytosol diminishes and the ability of purified nuclei to incorporate gluocorticoids in vitro increases. These observations suggest that the relative distribution between cytosol and nucleus of glucocoriticoid binding sites is dependent upon the concentration of available steroids. (Endocrinology94: 377, 1974)