Evidence for a New Class of Corticosterone Receptors in the Rat Kidney1

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Abstract
Recent studies have documented the properties of high affinity renal cytoplasmic receptors for aldosterone (Type I ), and for glucocorticoids (Type II) which bind dexamethasone with about twice the affinity shown for corticosterone. We now present evidence for the existence of a third class of renal cytoplasmic receptors (Type III) which resemble but are probably distinct from plasma corticosteroid—binding globulin (CBG). The Type III sites have a high affinity for corticosterone, Kdisg = 3 X 10–9M at 25 C, and very low affinities for both aldosterone and dexamethasone. The Type III receptors follow saturation kinetics in the binding of 3H—corticosterone, and the relative affinities of various steroids for these sites is in the following sequence: corticosterone > cortisol > deoxycorticosterone > progesterone > aldosterone > dexamethasone. Within the kidney, the inner medullapapilla showed substantially higher concentrations of Type III receptors than the outer cortex. The protein nature of the type III receptor is suggested by susceptibility to trypsin and pronase treatment. Bound 3H—corticosterone was shown to be unmetabolized by extraction and co—chromatography with authentic corticosterone. Type III receptors exhibit affinities for a variety of steroids indistinguishable from those of CBG. Type III receptors, however, differ from CBG in several respects: 1) The 3H—corticosterone—Type III complex dissociated at a faster rate than the CBG complex at 0 C. 2) Type III receptors sedimented at 8 S and 4 S in low Ca++ media whereas CBG sedimented only at 4 S. 3) In vivo, injection of 100-fold excess of corticosterone reduced 3H— corticosterone binding to the renal Type III receptors to 30% of the control value, but had no appreciable effect on the binding of 3H—corticosterone to CBG. 4) Type III receptors serve as donors for nuclear 3H—corticosterone uptake; KCl—extractable nuclear complexes were obtained from both cortex and medulla—papilla, and shown to sediment at 3 S in sucrose density gradients. (Endocrinology92: 1429, 1973)

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