Regulation of hepatic glucocorticoid receptor during development of mice

Specific binding of [3H]dexamethasone to its intracellular receptors and the subsequent activation of hormone-receptor complexes were studied in the liver of mice at various postnatal ages. The results indicate that the level (fmol/mg protein) of receptors is significantly higher in the liver of 30-day old mice as compared to other ages studied. Scatchard analysis of binding data exhibits no change in the affinity of hormone to receptor during development. The magnitude of both temperature- and salt-dependent activation of glucocorticoid receptor shows no change in 10- and 60-day old mice, as judged by DNA-cellulose binding. Whereas nuclear binding of temperature activated hormone-receptor complexes is more pronounced in 10-day old mice. Cross-mixing experiments indicate nuclear specificity. DNase I digestion studies showed higher extractability of bound [3H]dexamethasone-receptor complexes from nuclei of 10-day (70%) as compared to 60-day (46%) old mice. These findings indicate changes in the hepatic glucocorticoid receptor level and also in the nature of chromatin organization during development, which might play an important role in the glucocorticoid action mechanism in developing animals.