IMMUNOHISTOCHEMICAL EVALUATION OF THE EFFECT OF TZP-4238 - POSSIBLE ANDROGEN RECEPTOR ANTAGONIST IN RAT PROSTATE

Rat prostate was stained immunohistochemically using polyclonal androg en receptor antibody. A rabbit polyclonal antibody referred as NH27 wa s raised against human androgen receptor. Male Sprague-Dawley rats wer e divided into four experimental groups. Group 1 consisted of intact c ontrols. In group 2, rats were sacrified two days after castration. In group 3, rats were administered subcutaneously 1 mg/ animal of testos terone daily for three days after two days of castration. In group 4, rats were given 10 mg/ kg of TZP-4238, an anti-androgen agent, orally by gavage once a day for 1 week. Frozen sections of the prostates were fixed in Zamboni's fixative. The sections were incubated overnight at 4 degrees C with NH27. In the control rat prostate, positive staining for the antibody appeared in nuclei of the glandular epithelium. In a ddition, immunodetectable androgen receptor remarkably decreased 2 day s after castration and returned to intact levels after testosterone-ad ministration in the castrated rats. These findings are in agreement wi th results of previous work on the prostate. Furthermore, nuclear immu nostaining of the androgen receptor remarkably decreased after the tre atment with TZP-4238. The precise mechanism which produces atrophy of the prostatic glandular epithelium is not yet clear from the present s tudy. We further speculated that TZP-4238 was considered to be a stero idal androgen receptor antagonist. It is concluded that immunohistoche mical analysis using NH27 may be a very useful method for predication of the effects of anti-androgen treatment for rats.