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

Abstract

A steroidal anti-androgen TSSA-291 ( 16\ g=b\ \ x=r eq-\ ethyl-17\g=b\-hydroxy-4-oestren-3-one) bound to a macromolecular component in the cytosol of rat ventral prostates with high affinity (Kd = 5.0 \m=x\10\m=-\9 m) and in a saturable manner. The number of binding sites was comparable to that for 5\g=a\-dihydrotestosterone( 5\ g=a\ \ x=r eq-\ DHT).[3H]TSAA-291 binding was effectively displaced by unlabelled 5\g=a\-DHT,19-nortestosterone and cyproterone acetate but to a lesser degree by corticosterone. Glycerol density-gradient centrifugation analysis revealed that the sedimentation coefficeint of the [ 3H] \ x=r eq-\ TSAA-291-macromolecule complex was 3\p=n-\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\p=n-\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\g=a\-DHT\x=req-\ 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.