Increased levels of clusterin (SGP-2) mRNA and protein accompany rat ventral prostate involution following finasteride treatment

Finasteride is a well-known inhibitor of the prostatic enzyme 5 alpha -redu ctase type 2 which prevents conversion of testosterone into 5 alpha -dihydr otestosterone, the active intraprostatic androgen, which causes prostate in volution through a combination of cell atrophy and cell death. The drug is widely used to improve symptoms of benign prostatic hyperplasia in man. Clu sterin, a glycoprotein which is generally up-regulated under conditions ind ucing cell atrophy or organ involution, is produced at a high level in the regressing rat ventral prostate following androgen ablation. According to s everal authors, clusterin does not respond to finasteride treatment, sugges ting a different action of testosterone and 5 alpha -dihydrotestosterone. W e show here that, under our conditions, finasteride was capable of inducing production of both clusterin mRNA and protein in the rat ventral prostate. In fact, by using different and converging techniques, such as Northern hy bridization, in situ hybridization histochemistry and immunohistochemistry, we were able to show a strong induction of the clusterin gene in the epith elial cell population of the gland. The response to finasteride, which was similar to that seen with castration, occurred with a delay of a few days. In situ and immunohistochemistry experiments indicated that both orchidecto my and finasteride administration resulted in increased transition of the e pithelial cells from the columnar to the cuboidal (atrophic) shape, and thi s was accompanied by an increased intensity of the signal for clusterin. Th us, it appears that induction of clusterin is part of the molecular process leading to prostate involution caused by either orchidectomy or finasterid e administration.