Rs. Rittmaster et al., EVIDENCE FOR ATROPHY AND APOPTOSIS IN THE VENTRAL PROSTATE OF RATS GIVEN THE 5-ALPHA-REDUCTASE INHIBITOR FINASTERIDE, Endocrinology, 136(2), 1995, pp. 741-748
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.