Studies on the Origin of Androstanediol and Androstanediol Glucuronide in Young and Elderly Men*

Abstract

The in vivo origin of androstanediol (3 alpha diol) and its glucuronide was studied in six young and five elderly men undergoing cardiac catheterization. Constant infusions of [14C]testosterone and [3H]3 alpha diol were given, and blood was obtained from the aorta and hepatic vein in order to measure metabolic clearance, splanchnic extraction, and the possibility of splanchnic production of both 3 alpha diol and its glucuronide. In young elderly men, the concentrations of labeled and unlabeled testosterone, dihydrotestosterone, and 3 alpha diol were lower in the hepatic vein than in the aorta. The specific activities of dihydrotestosterone and 3 alpha diol were the same in blood entering and leaving the splanchnic compartment. The plasma concentration of 3 alpha diol was 18 +/- 2 in the young men and 15 +/- 4 ng/dl in the elderly group. However, the blood production rate of 3 alpha diol determined from the metabolic clearance and morning plasma concentration was reduced (324 vs. 199 micrograms/day) as a result of lower clearance in the elderly men. Plasma 3 alpha diol glucuronide concentrations were 197 +/- 68 and 96 +/- 35 ng/dl in the two groups. No difference in the concentration of 3 alpha diol glucuronide was observed across the splanchnic tissues by mass, radioactive levels, specific activity, or 14C to 3H ratios. The 14C to 3H ratio for 3 alpha diol glucuronide was 10 times higher than for the free steroid, indicating that more than 90% of the glucuronide originates from a pool separate from blood 3 alpha diol. Both the splanchnic extraction of 3 alpha diol and the metabolic clearance were reduced in elderly men. These studies indicate that both 3 alpha diol and its glucuronide in blood result from extrasplanchnic events. A major reduction in the plasma concentration of 3 alpha diol glucuronide occurs in the aging male, although no difference is seen in the levels of the unconjugated 3 alpha diol. 3 alpha diol and its glucuronide are derived principally by extrahepatic (target) tissue events.