As. Wright et al., RELATIVE POTENCY OF TESTOSTERONE AND DIHYDROTESTOSTERONE IN PREVENTING ATROPHY AND APOPTOSIS IN THE PROSTATE OF THE CASTRATED RAT, The Journal of clinical investigation, 98(11), 1996, pp. 2558-2563
Although dihydrotestosterone (DHT) is the principal androgen in the pr
ostate, testosterone can also act as an androgen in this tissue. To de
termine the relative potencies of testosterone and DHT in preventing p
rostate regression, castrated rats were implanted for 4 d with varying
doses of testosterone in the presence or absence of the 5 alpha-reduc
tase inhibitor finasteride. In the absence of finasteride, testosteron
e in the prostate is converted to DHT, creating an intraprostatic DHT
dose response. In the presence of finasteride, this conversion is bloc
ked, and an intraprostatic testosterone dose response is achieved. DHT
was 2.4 times more potent than testosterone at maintaining normal pro
state weight and duct lumen mass, a measure of epithelial cell functio
n. The two androgens were equipotent at preventing DNA fragementation
and expression of testosterone-repressed prostate message, two measure
s of apoptosis (cell death). The intraprostatic testosterone concentra
tion that results from finasteride treatment in rats is sufficient to
inhibit apoptosis but will not maintain normal epithelial cell activit
y. In conclusion, whereas DHT is more potent than testosterone at stim
ulating prostate epithelial cell function as measured by ductal mass,
the two androgens are equipotent at preventing prostate cell death aft
er castration. These results explain why finasteride causes prostate i
nvolution in the rat with minimal evidence of prostate cell death.