This grant application is a renewal of an ongoing project to describe the in vivo aspects of androgen metabolism in adult and elderly men with BPH. In the current project period we wish to study androgen kinetics using tracer testosterone, dihydrotestosterone and androstanediol. In one experiment we wish to determine the fate of testosterone entering the splanchnic compartment (liver). Analysis will be made of radioactivity (3H and 14C) as well as mass of these free steroids and glucuronides entering and leaving the splanchnic tissues utilizing opportunities provided during cardiac catheterization. This work will further determine whether splanchnic tissues play a role in extraglandular production of testosterone and adrostanediol glucuronides and free DHT and DHT glucuronide. In a second project we will determine whether T and DHT production and interconversion is altered in patients with premature prostate hyperplasia (ages 41-59) versus age controlled normals. In a separate study the effect of a partial or complete prostatectomy on androgen production and androgen kinetics will be measured to explore whether the changes in T/DHT production, noted by us in BPH patients, is the result of prostate production of DHT or an effect of other extrasplanchnic tissues. Finally, a study on the effect of chronic illness on DHT production will be carried out to see if there is an analogy with block in thyroxin-T3 conversion observed recently in a number of disease states.
