Induction of progesterone receptor with 17 beta-estradiol in human ovarian cancer.

We utilized a xenograft model of human ovarian cancer to study the ability of estrogen to induce progesterone receptor. Tumor cytosol from 17 beta-estradiol treated oophorectomized animals, but not oophorectomized controls, contained a [3H]ORG 2058 binding moiety of sedimentation coefficient 6-9S. This component showed specificity for the progestagens: progesterone, ORG 2058, and R5020 and for the antiprogestagen cyproterone acetate. At 1000-fold molar excess, 5 alpha-dihydrotestosterone competed partially for these sites while diethylstilbestrol, dexamethasone, and the antiandrogen, SCH 16423, were ineffective competitors. The dissociation constant for this progestagen binding entity was 0.14 nM using [3H]ORG 2058 as labeled ligand and R5020 as competitor. In addition, saturation analysis demonstrated that approximately 400 fmol of progestagen specific binding capacity was available per mg of cytosol protein. These data suggest that estrogen can induce progesterone receptor in human ovarian carcinoma.