Equivalent affinity of aldosterone and corticosterone for type I receptors in kidney and hippocampus: Direct binding studies

In studies from several laboratories evidence has been adduced that renal Type I (mineralocorticoid) receptors and hippocampal “corticosterone-preferring” high affinity glucocorticoid receptors have similar high affinity for both aldosterone and corticosterone. In all these studies the evidence for renal mineralocorticoid receptors is indirect, inasmuch as the high concentrations of transcortin (CBG) in renal cytosol make studies with [ 3H]corticosterone as a probe difficult to interpret, given its high affinity for CBG. We here report direct binding studies, with [ 3H]aldosterone and [ 3H]corticosterone as probes, on hippocampal and renal cytosols from adrenalectomized rats, in which tracer was excluded from Type II dexamethasone binding glucocorticoid receptors with excess RU26988, and from CBG by excess cortisol 17β acid. In addition, we have compared the binding of [ 3H]aldosterone and [ 3H]corticosterone in renal cytosols from 10-day old rats, in which CBG levels in plasma and kidney are extremely low. Under conditions where neither tracer binds to type II sites or CBG, they label an equal number of sites (kidney 30–50 fmol/mg protein, hippocampus ~200fmol/mg protein) with equal, high affinity ( K d 4°C 0.3–0.5 nM). Thus direct tracer binding studies support the identity of renal Type I mineralocorticoid receptors and hippocampal Type I (high affinity, corticosterone preferring) glucocorticoid receptors.