Cyproterone acetate prevents translocation of the androgen receptor in the rat prostate.
The translocation of the androgen receptor in prostatic tissue has been studied under the influence of different ligands (testosterone, methyltrienolone and cyproterone acetate) in vivo and in vitro. Nuclear and cytoplasmic androgen receptors were estimated using an exchange assay with [3H]methyltrienolone ( [3H]R1881) 1 h and 16 h after injection in castrated rats of either 100 micrograms testosterone (T), 10 mg cyproterone acetate (CA) or the combination of T and CA. Within 1 h after T administration, nuclear receptor levels increased with a concomitant depletion of cytosol receptors. In the CA-treated rats nuclear receptor levels were not different from those of control castrated animals and there was no depletion of cytosol receptors. The combined treatment of T and CA resulted in a partial depletion of cytosol receptors and a simultaneous increase of nuclear receptors. The absence of an increase in nuclear androgen receptors in CA-treated animals cannot be explained by a delay in translocation, because even 16 h after CA injection, only a very small number of nuclear receptors were detectable. Incubation of minced prostatic tissue with [3H]CA or [3H]R 1881 resulted in receptor translocation only in the R1881 incubations and confirmed the in vivo results. Competition studies with different steroids and cytosol receptor (non-activated, 8S form in low salt gradient) or nuclear receptor (activated 3.6S form in high salt gradient) of prostatic tissue show that CA can compete with R1881 for specific androgen-binding sites with a similar relative binding affinity for both receptor preparations. The present results provide evidence that CA prevents translocation of the androgen receptor to the nucleus, although CA can be bound with similar affinities to the nuclear receptor and the cytoplasmic receptor. We propose that the anti-androgenic action of CA involves an inhibition of receptor translocation.
D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D003534:Cyproterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017373:Cyproterone Acetate; D004963:Estrenes / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D015741:Metribolone; D011467:Prostate / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*
D000726:Androgen Antagonists; D004963:Estrenes; D011944:Receptors, Androgen; D011987:Receptors, Steroid; D015741:Metribolone; D017373:Cyproterone Acetate; D003534:Cyproterone