Production and metabolism of dihydrotestosterone in peripheral tissues

The production and metabolism of dihydrotestosterone (DHT) was studied in 10 normal men using constant infusions of [7-3H]-delta 4 -androstenedione (A)/[4-14C]DHT (6 men) or of [7-3H]testosterone (T)/[4-14C]DHT (4 men) with measurement of radioactivity as precursor and product in the brachial artery, and a superficial vein (draining primarily adipose tissue) and deep vein (draining primarily muscle) in the arm opposite to the infusion. The metabolic clearance rates (MCR) were (mean +/- SE) 560 +/- 55, 1620 +/- 80, and 790 +/- 65, 1/day for DHT, A and T respectively. The overall conversions (percent of A or T infused which was measured as DHT in arterial blood) were 2.3 +/- 0.8% and 2.7 +/- 0.5% for A to DHT and T to DHT. Of the DHT entering the adipose tissue 13.8 +/- 3.4% was metabolized and of that entering muscle 5.8 +/- 1.8% was metabolized. On the basis of assumed blood flows, adipose tissue and muscle metabolism each carry out approx. 7-8% of the overall metabolism of DHT. Of the A entering the forearm adipose tissue 1.9 +/- 0.5% was converted to DHT. Extrapolated to the body's adipose tissue, this represents 14% of the total A converted to DHT. Of the T entering the forearm adipose tissue 1.2 +/- 0.3% was converted to DHT. Extrapolated to the body's adipose tissue, this represents 6% of the total T converted to DHT. In three out of six subjects infused with A/DHT and in three out of four subjects infused with T/DHT small gradients indicating conversion of A and T to DHT by tissues drained by the deep vein were found. The mean value for the conversion of A to DHT across the deep vein tissues was 0.84 +/- 0.51% and for T to DHT was 0.28 +/- 0.12%. Both adipose tissue and muscle metabolize DHT but only adipose tissue appears to play a role in the conversion of A and T to DHT.