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

Abstract

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