Specific interaction of radioactive anti-androgen TSAA-291 with androgen receptor in rat prostates.

A steroidal anti-androgen ISSA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) bound to a macromolecular component in the cytosol of rat ventral prostates with high affinity (kd = 5.0 X 10-9 M) and in a saturable manner. The number of binding sites was comparable to that for 5 alpha-dihydrotestosterone (5 alpha-DHT). [3H]TSAA-291 binding was effectively displaced by unlabelled 5-alpha-DHT, 19-nortestosterone and cyproterone acetate but to a lesser degree by corticosterone. Glycerol density-gradient centrifugation analysis revealed that the sedimentation coefficient of the [3H]-TSAA-291-macromolecule complex was 3-4.5 S. However, when the unlabelled cytosol was fractionated by glycerol density-gradient centrifugation before the binding of [3H]TSAA-291 was examined, specific binding of [3H]TSAA-291 was observed in fractions corresponding to 8-10 S. Binding of the [3H]TSAA-291-macromolecules complex to prostatic nuclei and DNA-cellulose was considerably less than binding by the [3H]5 alpha-DHT-macromolecule complex. Instability of the TSAA-291 binding component on heat treatment before and after complex formation was also revealed and the results are discussed in terms of the anti-androgenic activity of TSAA-291.