The Endocrine Background of Human Renal Cell Carcinoma

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Abstract
To investigate whether progestins may trigger tumor regression by a mechanism involving the glucocorticoid receptor, human renal cell carcinomas obtained from 15 patients were analyzed for cytoplasmic glucocorticoid-binding components, using [3H] dexamethasone. The existence of glucocorticoid binders could be demonstrated in 10 out of 15 tumors studied. The average binding capacity was calculated at 7.1 femto mol/mg of cytosol protein. The apparent dissociation constant determined in the cell-free system amounted to 1.9 .times. 10-8 mol/l. The ligand specificity experiments clearly indicated that binding to these receptors is not restricted to glucocorticoids alone. Progesterone and aldosterone turned out to be moderate competitors for dexamethasone binding. Medroxyprogesterone acetate, the compound widely used in hormone therapy of advanced renal cancer in man, was demonstrated to be one of the strongest inhibitors of [3H] dexamethasone. Binding of medroxyprogesterone acetate to glucocorticoid receptors might represent the primary mechanism of action of the compound in causing tumor regression.

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