Anti-androgen TSAA-291. VI. Effects of the anti-androgen TSAA-291 and its related compounds on the in vitro formation of 5 alpha-DHT-receptor complex in the cytosol of rat ventral prostates.

Inhibitory effect of a synthetic steroidal anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) on the in vitro formation of 5 alpha-dihydrotestosterone(5 alpha-DHT)-receptor complex was examined. An aliquot of the cytosol from rat ventral prostates was incubated with [3H]5 alpha-DHT in the presence of various amounts of the anti-androgen. By means of dextran-coated charcoal assay and sucrose density-gradient centrifugation analysis, TSAA-291 was demonstrated to inhibit directly, in a competitive manner, the binding of 5 alpha-DHT to a component analogous in its properties to the cytosol androgen receptor. Further, displacing study using a variety of TSAA-291 analogues was undertaken to examine which of the functional groups of TSAA-291 is important for the affinity to the 5 alpha-DHT binding component, and elucidated that 3-hydroxy or 5 alpha-dihydro derivatives of TSAA-291 and others having axial methyl group at C-10 were less potent competitors for [3H]5 alpha-DHT binding than TSAA-291. Furthermore, using other steroids including androgens and anti-androgens, considerable knowledge was obtained about structural requirements for a steroid molecule to displace the bound [3H]5 alpha-DHT, and this displacing activity of the steroids was discussed in terms of their anti-androgenic activity.