Abstract
The effect of a synthetic steroidal anti-androgen, TZP-4238, on steroid-induced rat dorsolateral prostatic hyperplasia was investigated. Male Sprague-Dawley rats were divided into five experimental groups. Group 1 consisted of intact controls. The other animals were castrated. The castrated animals were treated for seven weeks with 1) testosterone 1mg/animal plus 17β-estradiol (E2) 10μg/animal (Group 2), 2) testosterone plus E2 plus TZP-4238 2mg/kg (Group 3), 3) testosterone plus E2 plus TZP-4238 8mg/kg (Group 4) and 4) testosterone plus E2 plus Tween 80 (Group 5) instead of TZP-4238. TZP-4238 was administered orally for four weeks after three weeks of treatment with testosterone plus E2. In groups 2 and 5, glandular hyperplasia of the dorsolateral prostate was clearly observed, and the fibro-muscular stromal proliferation was also noted. The glandular epithelial cells showed uniformly intense nuclear immunostaining for androgen receptors (AR). Furthermore, AR was also localized in the nuclei of the proliferated fibromuscular cells. In contrast, combined treatment with TZP-4238 (Groups 3 and 4) produced inhibition of the glandular hyperplasia. Furthermore, nuclear immunostaining of AR of both epithelial and stromal cells was remarkably decreased. These results indicate that the uptake of testosterone and/or its androgenic effect on the dorsolateral prostate may be suppressed by TZP-4238. Furthermore, the decreased AR immunostaining may be explained by the decrease in number of AR and/or antibody binding site for AR.
