RELATIVE POTENCY OF TESTOSTERONE AND DIHYDROTESTOSTERONE IN PREVENTING ATROPHY AND APOPTOSIS IN THE PROSTATE OF THE CASTRATED RAT

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.