Glucocorticoid-binding Macromolecules in Normal Tissues and Tumors

Abstract

Abstract A simple cell-free system was developed for studying specific binding components for glucocorticoids in normal as well as neoplastic tissues of the mouse. The steroid-macromolecular complex was extracted from the lymphosarcoma P1798 as a 27,000 x g supernatant fraction and separated from free steroid by gel chromatography. When 9α-fluoro-11β-16α,21-tetrahydroxy-pregna-1,4-diene-3,20-dione-16,17-acetonide (triamcinolone acetonide) was present at the time of cell breakage, the results indicate that the binding process is not complicated by degradation of the binding component. Triamcinolone acetonide protected the binding component from spontaneous degradation. The rate of degradation of the binding component in the presence of this potent synthetic glucocorticoid is approximately one-eightieth of that of the unprotected component. The specificity of the binding component was demonstrated by the finding that 11β,17α,21-trihydroxypregn-4-ene-3,20-dione (cortisol) depressed the binding of [1,2,4-3H3]triamcinolone acetonide by 90%, whereas the biologically inactive stereoisomer, 11α, 17α,21-trihydroxypregn-4-ene-3,20-dione (11-epicortisol), reduced the binding by only 20%. The resistant subline of the tumor binds less [1,2,4-3H3]-triamicinolone acetonide in a specific manner in comparison to the sensitive neoplasm. Adrenalectomy causes an increase in specific binding of [1,2,4-3H3]triamcinolone acetonide in the glucocorticoidsensitive lymphosarcoma P1798. A soluble macromolecular fraction from the thymus binds 3 times more [1,2,4-3H3]-triamcinolone acetonide than the corresponding fraction from either the testis or cerebral cortex.