Although the functional role of TRPM-2/clusterin in the prostate remains controversial, it has been postulated that transcriptional activation of the gene is an important mechanism in castration-induced prostatic involution and perhaps is a means for prostatic cells to escape apoptotic induction. In the present study, we have measured expression levels of TRPM-2/clusterin and apoptotic activities in the prostates of castrated Noble (NBL) rats and those treated with testosterone (T) and estradiol-17beta (E2) for 16 weeks. We have previously shown that the combined sex hormone treatment (T+E2) induces dysplasia, a purported preneoplastic lesion, exclusively in the dorsolateral prostates (DLPs) of all treated rats. In the present study, we demonstrate that, as expected, castration readily induced enhanced TRPM-2/clusterin expression, which was accompanied by increased apoptotic activity in the epithelia of DLP and ventral prostate (VP). The increase in TRPM-2/clusterin expression appeared earlier and was more dramatic in the VP than in the DLP. In sharp contrast, treatment of rats with T+E2 for 16 weeks induced augmentation of TRPM-2/clusterin expression selectively in the dysplastic lesions of the DLP but not in the lesion-free VP. The enhanced expression of TRPM-2/clusterin in the dysplastic epithelium was, however, not attended by an increase in apoptotic activity within the lesion. Thus, the observed up-regulation of TRPM-2/clusterin expression in the dysplastic foci of T+E2-treated rats occurred in animals whose androgen status remained normal and, despite the increased level of expression of this gene, apoptotic activity in these lesions was unchanged from basal values measured in the DLPs of untreated rats. These findings suggest that TRPM-2/clusterin expression in dysplastic lesions was no longer repressed by androgen nor was it associated with apoptosis. We propose that overexpression of the gene is likely a phenotype of neoplastic transformation. In addition, we speculate that TRPM-2/clusterin may serve as a survival factor, which could favor accumulation of transformed cells in dysplastic foci and thus promote the carcinogenic process.