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.

Benign Prostatic Hyperplasia: a Disorder of Androgen Metabolism in the Male

“…The data indicates that neither by mass, radioactivity or specific activity is there any evidence for production of DHT by gut, liver, or splanchnic fat from testosterone or any other steroid entering or produced by splanchnic tissue [32,33]. This conclusion is similar to those reached by us for androstanediol [34]. Therefore, we can conclude that these androgen interconversions occur in extrasplanchnic tissues.…”

3 alpha, 17 beta-androstanediol glucuronide in plasma. A marker of androgen action in idiopathic hirsutism.

“…Purification of the extracted steroid was by a celite column where 3a-diol and DHT are clearly separated from testosterone and other C-19 ketosteroids. 3a-diol glucuronide was also measured as previously described (16). Additional characteristics of the assay include: precision 9%, nonspecific blank 6±3 pg, and recovery 86%.…”

“…In a series of studies we have demonstrated that DHT and 3a-diol in plasma originates from peripheral conversion of secreted precursors (testosterone and androstenedione) (13,14). Our most recent studies suggest that DHT, 3a-diol and 3a-diol glucuronide in plasma are derived in large part from extrasplanchnic metabolism and that >90% of the glucuronide originates from a pool separate from blood 3a-diol (15,16).…”

Clinical Assessment and Serum Hormonal Profile in Prepubertal Hypertrichosis

“…The sensitivity of the assay was 0.01 nmol/ml and 0.15 pmol/ml, respectively; the intra- and interassay coefficients of variation were 14.8 and 16.6%, respectively. 3α-Androstanediol glucuronide was measured by RIA after extraction with ether and serum hydrolysis with 300 units of β-glucuronidase, following a modified procedure of the technique originally described by Marimoto et al [18]. The intra- and interassay coefficients of variation were 4.6 and 6.8%, respectively.…”