The source of plasma dihydrotestosterone (DHT) (17β-hydroxy-5α-androstan-3-one) in humans has been investigated by infusing two potential peripheral precursors, testosterone (T) and androstenedione (A). Metabolic clearance rates (MCR), conversion ratios (CR), transfer constants (ρ), and blood production rates (PB) were calculated. Plasma testosterone and dihydrotestosterone were measured by competitive binding techniques. The MCRDHT was 652 ±35 (SD) liters/day in five males and 314 ±63 (SD) liters/day in four adult females. In each individual, the MCRDHT was significantly lower than MCRT as predicted by testosterone-binding protein affinity studies. The PBDHT was 302 ±65 (SD) μg/day in males and 56 ±26 μg/day in females. Testosterone and androstenedione are precursors (prehormones) for plasma dihydrotestosterone. The conversion ratio CRBBT-DHT, calculated as the ratio of counts per minute per liter of plasma of product to precursor after infusion of labeled precursor, was 5.6 ±0.6 (SD)% (six subjects) in the male and 3.5 ±0.4 (SD)% (four subjects) in the female. CRBBA-DHT after androstenedione infusion to three female subjects averaged 9.2%. No dihydrotestosterone back conversion was detected (< 0.2%). The transfer constants were [ρ]BBT-DHT, 3.9 ±1.0% (male) and 1.7 ±0.6% (female), and [ρ]BBA-DHT average was 13.3% in three female subjects. Using either plasma testosterone and dihydrotestosterone values from our subjects and mean androstenedione values as reported in the literature, approximate contributions can be calculated. Testosterone conversion accounts for at least 70% of plasma DHT in the male, but less than 20% in the normal female. Androstenedione appears to be a major prehormone of plasma dihydrotestosterone accounting for at least two-thirds plasma dihydrotestosterone by peripheral conversion in adult females. In three normal women undergoing tubal ligation, there was an unimpressive gradient between ovarian vein and peripheral plasma dihydrotestosterone. It is suggested that dihydrotestosterone in the blood does not arise from direct secretion but may reflect events occurring in peripheral androgen target tissues.
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