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

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Rat prostate was stained immunohistochemically using polyclonal androgen receptor antibody. A rabbit polyclonal antibody referred as NH27 was raised against human androgen receptor. Male SpragueDawley rats were divided into four experimental groups. Group 1 consisted of intact controls. In group 2, rats were sacrified two days after castration. In group 3, rats were administered subcutaneously 1mg/ animal of testosterone daily for three days after two days of castration. In group 4, rats were given 10mg/ 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°C with NH27. In the control rat prostate, positive staining for the antibody appeared in nuclei of the glandular epithelium. In addition, immunodetectable androgen receptor remarkably decreased 2 days after castration and returned to intact levels after testosterone-administration in the castrated rats. These findings are in agreement with results of previous work on the prostate. Furthermore, nuclear immunostaining of the androgen receptor remarkably decreased after the treatment with TZP-4238. The precise mechanism which produces atrophy of the prostatic glandular epithelium is not yet clear from the present study. We further speculated that TZP-4238 was considered to be a steroidal androgen receptor antagonist. It is concluded that immunohistochemical analysis using NH27 may be a very useful method for predication of the effects of antiandrogen treatment for rats.