The endocrine background of human renal cell carcinoma. IV. Glucocorticoid receptors as possible mediators of progestogen action

Abstract

In order to investigate whether progestins may trigger tumour regression by a mechanism involving the glucocorticoid receptor, human renal cell carcinomas obtained from 15 patients were analysed for cytoplasmic glucocorticoid-binding components, using [3H] dexamethasone. The existence of glucocorticoid binders could be demonstrated in 10 out of 15 tumours studied. The average binding capacity was calculated and found to be 7.1 fmol/mg of cytosol protein. The apparent dissociation specificity experiments clearly cell-free system amounted to 1.9 X 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. It is concluded that binding of medroxyprogesterone acetate to glucocorticoid receptors might represent the primary mechanism of action of the compound in causing tumour regression.