EVIDENCE FOR ATROPHY AND APOPTOSIS IN THE VENTRAL PROSTATE OF RATS GIVEN THE 5-ALPHA-REDUCTASE INHIBITOR FINASTERIDE

Castration causes cell loss in the rat Ventral prostate through a proc ess called apoptosis. Although 5 alpha-reductase inhibition also cause s prostate cell loss, the mechanisms involved have been debated. To in vestigate this question further, we have evaluated the histological re sponses of the rat ventral prostate to both castration and 5 alpha-red uctase inhibition. Rats were left intact, castrated, or given the sele ctive 5 alpha-reductase inhibitor finasteride. After 4, 9, 14, and 21 days the prostates were excised, the androgen and DNA content determin ed, and the tissue was subjected to histological and histomorphometric analysis. Finasteride and castration decreased prostate weight at day 21 by 65% and 93%, respectively. Castration decreased DNA content (mi crograms per prostate) by a maximum of 88% at 14 days. Finasteride had no significant effect on DNA content after 4 days and decreased DNA c ontent by a maximum of 52% at 14 days. When castrate prostate sections were stained for tissue transglutaminase, a marker of apoptotic cell death, a maximum of 23% of epithelial cells were stained by day 14 wit h a return to control levels by day 21. Finasteride caused a less inte nse increase in staining in which 16% of epithelial cells stained for tissue transglutaminase on day 9 with a return to baseline by day 14. When prostate sections were stained for DNA breaks, another marker of cell death, castration, caused a peak of staining on day 4 with 6% of epithelial cells staining and a return to near control levels by day 2 1. Finasteride-induced staining was less intense with peak staining at day 4 (0.7% of epithelial cells) and a return to control values by da y 9. Morphometrics were used to assess the effect of castration and fi nasteride on prostate duct size and epithelial cell mass. After 4 days of finasteride treatment, the mean ductal mass decreased by 47%, with no significant change thereafter. The mean epithelial cell mass decre ased by 15% on day 4 and 60% on day 9, with no further decrease therea fter. Castration caused a more rapid and greater decrease in both morp hometric parameters with a 95% reduction in the mass of prostate ducts and a 93% decrease in epithelial cell mass by day 9. We conclude that castration induces a more profound involution of the rat ventral pros tate than does 5 alpha-reductase inhibition. Cell loss occurs in both groups, but the degree of cell loss is less with finasteride. The pres ence of an increased number of apoptotic cells in the 4- and 9-day fin asteride-treated animals, compared with controls, suggests that the pr ostatic involution seen with finasteride is due in part to apoptosis. Intraprostatic dihydrotestosterone concentrations were similar in the finasteride-treated and castrate rats, indicating that the increased c oncentration of testosterone in the finasteride-treated rats attenuate s the degree of androgen deprivation induced by finasteride.