VI. EFFECTS OF THE ANTI-ANDROGEN TSAA-291 AND ITS RELATED COMPOUNDS ON THE IN VITRO FORMATION OF 5α-DHT-RECEPTOR COMPLEX IN THE CYTOSOL OF RAT VENTRAL PROSTATES

Abstract

ABSTRACT Inhibitory effect of a synthetic steroidal anti-androgen TSAA-291 (16β-ethyl-17β-hydroxy-4-oestren-3-one) on the in vitro formation of 5α-dihydrotestosterone(5α-DHT)-receptor complex was examined. An aliquot of the cytosol from rat ventral prostates was incubated with [3H]5α-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 5α-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 5α-DHT binding component, and elucidated that 3-hydroxy or 5α-dihydro derivatives of TSAA-291 and others having axial methyl group at C-10 were less potent competitors for [3H]5α-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] 5α-DHT, and this displacing activity of the steroids was discussed in terms of their anti-androgenic activity.