Comparative studies on the binding of cytoplasmic 3H-dexamethasone-receptor complex by nuclei from the livers of adult, newborn, and fetal rats

To gain insight into the mechanism of age-related changes in tissue responsiveness to gluco corticoids, the binding patterns of dexamethasone (Dex) to cytoplasmic receptor and of cyto plasmic Dex-receptor complex to nuclei were compared in the livers of adult, 7-day-old, new born and fetal rats. Only one binding component with high binding affinity was observed in the cytosol from the fetal liver, while at least 2 binders which showed high and low affinity to Dex were detected in the cytosol of the adult liver. Kd of the high-affinity binder in the cytosol of fetal liver was different from that in the adult liver; 3.6×10−10M for fetal and 9.1×10−10M for adult. Cytoplasmic Dex-receptor complexes from the adult and fetal liver were efficiently bound to nuclei from adult, 7-day-old, newborn and fetal livers. The amount of complex bound to nuclei of the adult liver was largest and the least binding was observed in nuclei of the newborn liver under the incubation conditions used, with 1.77 nM 3H-Dex-receptor complex. A high-affinity binding of the receptor complex from the adult liver was observed in fetal nuclei (Kd = 1 × 10−9M), but nuclei from the other tissues showed low-affinity and non-saturable binding. The Dex-receptor complex from the fetal liver bound to nuclei of the adult liver in a 1ow-afflnity and non-saturable manner, while high-affinity binding (Kd=6 × 10−10M) was observed in nuclei of the fetal liver. The binding of the fetal complex to nuclei of the 7-day-old and newborn livers showed a transitional binding pattern, with sites of high- and low-affinity binding coexisting. Based on these results, it was concluded that differences in the hepatic cytosol receptor-nuclear acceptor system may be attributable, at least in part, to age-related changes in tissue responsiveness to glucocorticoids.