DEMONSTRATION OF A PROGESTIN RECEPTOR IN HUMAN BENIGN PROSTATIC HYPERPLASIA AND PROSTATIC CARCINOMA

Abstract

Cytosol from human benign hyperplastic and carcinomatous prostatic tissue contained a progestin receptor with a dissociation constant of approximately 10-9 M. The receptor was measured using 3H-labeled R5020 (17.alpha.,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) as ligand. Progesterone, cyproterone acetate and R1881 (methyltrienolone) were efficient competitors to R5020 for binding sites on the receptor whereas testosterone, 5.alpha.-dihydrotestosterone, estradiol, cortisol and several hydroxylated and saturated derivatives of progesterone did not compete. The [3H]R 5020-receptor-complex had a sedimentation coefficient of approximately 4 S, an isoelectric point of approximately 5 was heat-labile and destroyed by treatment with trypsin but not DNase or RNase. Seventeen of 21 patients with benign prostatic hyperplasia and 3 patients with prostatic carcinoma had 1-40 fmol of specific R 5020-binding sites per mg of cytosol protein. One sample of normal prostatic tissue did not contain significant amounts of progestin receptor. Tissue specimens removed by transvesical adenoma enucleation displayed a larger number of specific R 5020 binding sites than electroresected specimens. The progestin receptor in hyperplastic prostate may be involved in the mechanism of action of progestins used in treatment of benign prostatic hyperplasia. Quantitation of progestin receptor in cancer of the prostate may form part of the basis of a predictive test program for endocrine therapy of prostatic malignancy.