The use of radioactive 7α, 17α‐dimethyl‐19‐nortestosterone (mibolerone) in the assay of androgen receptors

Abstract

Tritiated 7α, 17α‐dimethyl‐19‐nortestosterone (DMNT; mibolerone), a synthetic androgen stable to metabolic conversion in the rat ventral prostate, is an excellent radioactive ligand for the quantitation and characterization of androgen receptors in prostate, liver, and cultured cells. DMNT is more receptor‐selective than 17α‐methyl‐17β‐hydroxy‐estra‐4,9,11‐trien‐3‐one (R1881); DMNT interacts with glucocorticoid and progestin receptors much less strongly than R1881. Unlike 5α‐dihydrotestosterone, DMNT does not bind tightly to testosterone‐estradiol binding globulin of human serum. The hydroxylapatite‐filter assay we employed can clearly distinguish between DMNT binding to androgen receptors of rat ventral prostate and interaction of DMNT with androgen binding protein of epididymides. The prostate cytosol (³H)DMNT‐receptor complex sediments in two forms (4 and 8 S) in a low salt medium. In 0.4 M KCl, both the prostate cytosol and nuclear (³H)DMNT‐receptor complexes migrated as 3–4 S components. The formation of both the cytosol and nuclear DMNT‐receptor complexes is inhibited by antiandrogens and 17β‐estradiol.