GLUCOCORTICOID RECEPTORS IN THE MAMMALIAN INNER-EAR - RU-28362 BINDING-SITES

The effects of glucocorticoid hormones are thought to be initiated by binding of the steroid to stereospecific intracellular receptor proteins in target tissues. The synthetic glucocorticoid [H-3]-RU 28362, which demonstrates negligible affinity for mineralocorticoid (Type I) receptors [Philibert et al., (1983) Endocrine Sec. Abstr. 65, 335], was employed to identify the high-affinity glucocorticoid (Type II) receptors in the inner ear. By Scatchard analysis, the K-d of the [H-3]-RU 28362-cytoplasmic receptor complex was 11.4 X 10(-9) M for the lateral wall of the basal turn of the cochlea and 11.7 x 10(-9) M for the ampullae of the semicircular canals. The concentration of binding sites, B-max, was 240 fmol/mg dry tissue for the cochlear specimen and 89 fmol/mg dry tissue for the ampullae. Time course studies indicated that the binding of [H-3]-RU 28362 by inner ear tissues reached equilibrium within 30 min of incubation at 25 degrees C. Based on the total specific binding measured with [H-3]-RU 28362, the glucocorticoid receptor concentration in the lateral wall of the basal turn of the cochlea appears to exceed that in the ampullae of the semicircular canal by a factor of 2.7. Substantial specific [H-3]-RU 28362 binding to the cochlear lateral wail and ampullar tissue suggests the presence of glucocorticoid receptors and sites of glucocorticoid action in the inner ear.