3α-Androstanediol Kinetics in Man

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Abstract
Kinetics of 5α-androstane-3α, 17β-diol (3α-diol) were studied in man. Clearance rates were determined by both the constant infusion and single injection techniques. Production rates were calculated as the product of clearance rate data and plasma values in the a.m. obtained by a radioimmunoassay specific for 3α-diol. Mean metabolic clearance rates were 1,776±492 (SD) liters/day in males and 1,297±219 (SD) liters/day in females. Metabolic clearance rates by single injection were similar. Calculated production rates are 208±26 (SD) μg/day in males and 35±11 μg/day in females, which are significantly different. Hepatic extraction of 3α-diol determined by hepatic vein catheterization during constant infusion was 76% which was greater than expected from information on in vitro binding in plasma. The kinetic data is of interest since 3α-diol has a calculated inner pool (V1) volume of 12-14 liters, similar to 17β-hydroxyandrost-4-en-3-one (testosterone) and 5α-androstan-17β-ol-3-one (dihydrotestosterone), but the calculated outer pool (V2) of 33.5 liters is very large as are the metabolic rate and transfer constant. In contrast to testosterone and dihydrotestosterone, 3α-diol, although bound to sex hormone binding globulin, has a high metabolic clearance of which a large fraction represents extrahepatic (splanchnic) metabolism. A production rate of 3α-diol similar to dihydrotestosterone together with rather unique kinetic characteristics encourages further investigation of the biological role of this potent androgen.