Glucocorticoid Receptors in Adult and Senescent Rat Liver*

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Abstract
The physicochemical characteristics of hepatic glucocorticoid receptors in adult and old Sprague-Dawley rats were compared. In adult rats, a 50% difference in unoccupied receptor sites per U protein was found between intact and adrenalectomized rats. Interestingly, however, only about a 25% difference in the concentration of unoccupied hepatic glucocorticoid receptors was observed in old animals. Heat-activated (25 C for 45 min) steroid-receptor complexes from adult and old rats bound equally well to rat liver nuclei. Molybdate (10 mM) and N-ethylmalemide (10 mM) completely inhibited thermal activation in both age groups. However, Ca2+-dependent activation (0 C for 45 min) of the steroid-receptor complex was significantly lower in aged animals. No age-related differences were observed in either nonactivated or heat-activated [3H] dexamethasone-receptor complexes when analyzed on Sephadex G-100 or DEAE-cellulose columns. The stability of steroid-free hepatic glucocorticoid receptors was also similar in adult and old rats. On the other hand, time- and temperature-dependent inactivation of unbound receptors were more effectively inhibited by the addition of molybdate or molybdate plus dithiothreitol in aged animals than in adult rats. This age-dependent difference in chemical stabilization was also noted in studies using partially destabilized (30-min incubation at 25 C) receptors. Prebound steroid-receptor complexes appeared to be more stable in cytosol of adult rats than in that of older animals. The results presented herein suggest that hepatic glucocorticoid receptors in adult and old rats are similar in their affinities and in several physicochemical properties. However, these receptors do appear to differ significantly in their sensitivity to chemical stabilizers, in their in vitro low temperature activation by CaCl2, and in their unoccupied receptor concentration in intact animals.