Demonstration of a progestin receptor in human benign prostatic hyperplasia and prostatic carcinoma

Cytosol from human benign hyperplastic and carcinomatous prostatic tissue has been shown to contain a progestin receptor with a dissociation constant of approximately 10 ^-9M. The receptor was measured using ³H-labeled R 5020 (17α, 21-dimethyl-19 nor-4,9-pregnadiene-3,20-dione) as ligand. Progesterone, cyproterone acetate, and R 1881 (methyltrienolone) were efficient competitors to R5020 for binding sites on the receptor whereas testosterone, 5α-dihydrotestosterone, estradiols cortisol, and several hydroxylated and saturated derivatives of progesterone did not compete. The [ ³H]R 5020-receptor-complex had a sedimentation coefficient of approximately 45, an isoelectric point of approximately 5, was heat-labile, and was destroyed by treatment with trypsin but not with deoxyribonuclease or ribonuclease. Seventeen of 21 patients with benign prostatic hyperplasia and three patients with prostatic carcinoma had 1 to 40 fmoles 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 nucleation 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 the action of progestins used in the medical 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.