IMMUNOHISTOCHEMICAL STUDY OF ANDROGEN RECEPTOR IN RAT PROSTATIC HYPERPLASIA - EFFECT OF ANTIANDROGEN TZP-4238

The effect of a synthetic steroidal anti-androgen, TZP-4238, on steroi d-induced rat dorsolateral prostatic hyperplasia was investigated. Mal e Sprague-Dawley rats were divided into five experimental groups. Grou p 1 consisted of intact controls. The other animals were castrated. Th e castrated animals were treated for seven weeks with 1) testosterone 1 mg/animal plus 17 beta-estradiol(E(2)) 10 mu g/animal (Group 2), 2)t estosterone plus E(2) plus TZP-4238 2 mg/kg (Group 3), 3) testosterone plus E(2) plus TZP-4238 8 mg/kg (Group 4) and 4) testosterone plus E( 2) plus Tween 80 (Group 5) instead of TZP-4238. TZP-4238 was administe red orally for four weeks after three weeks of treatment with testoste rone plus E(2). In groups 2 and 5, glandular hyperplasia of the dorsol ateral prostate was clearly observed, and the fibro-muscular stromal p roliferation was also noted. The glandular epithelial cells showed uni formly intense nuclear immunostaining for androgen receptors (AR). Fur thermore, AR was also localized in the nuclei of the proliferated fibr omuscular cells. In contrast, combined treatment with TZP-4238 (Groups 3 and 4) produced inhibition of the glandular hyperplasia. Furthermor e, nuclear immunostaining of AR of both epithelial and stromal cells w as remarkably decreased. These results indicate that the uptake of tes tosterone and/or its androgenic effect on the dorsolateral prostate ma y be suppressed by TZP-4238. Furthermore, the decreased AR immunostain ing may be explained by the decrease in number of AR and/or antibody b inding site for AR.