Δ5-Androstenediol: Kinetics of Metabolism and Binding to Plasma Proteins in Normal Men and Women1

Abstract

Using the constant infusion and single injection technique the metabolic clearance rates (mean ± SEM) for Δ⁵-androstene-3β,17β-diol (Δ⁵-diol) were measured for 19 normal men (1311 ± 67 1/24 h) and 10 normal women (858 ± 63 1/24 h). The constant infusion technique yielded values for the conversion ratios for the transformation of Δ⁵-diol to several products: dehydroepiandrosterone (DHEA)/Δ⁵-diol of 0.06 ± 0.01 for men and 0.05 ± 0.01 for women, of Δ⁵-diol sulfate/Δ⁵-diol of 0.45 ± 0.04 for men and 0.52 ± 0.03 for women and of DHEA sulfate/Δ5-diol of 5.53 ± 0.26 for men and 5.02 ± 0.42 for women. The single injection technique yielded rate constants (units) and volumes of distribution (liters) for Δ⁵-diol; K₁ = 34.3 ± 4.3 for men and 35.0 ± 3.9 for women, K₂ = 63.7 ± 4.1 for men and 75.1 ± 4.2 for women, V₁ = 23.1 ± 3.2 for men and 11.9 ± 2.3 for women, V₂ = 14.8 ± 3.7 for men and 9.2 ± 3.2 for women. The mean Δ⁵-diol plasma concentration was 1.08 ± 0.10 ng/ml for 12 men and 1.17 ± 0.16 ng/ml for 9 women. The calculated blood production rates for Δ⁵-diol were 1357 ± 117 μg/24 h for 12 men and 969 ±131 μg/24 h for 9 women. The per cent binding (equilibrium dialysis) was higher for women (94.9 ± 0.3) than for men (93.0 ± 0.2). Paper electrophoresis showed that significant fractions of 3HΔ⁵-diol migrated with both the β-globulin and albumin fractions. Estrogen administration to two normal men increased the per cent binding of Δ⁵-diol to plasma proteins and decreased the metabolic clearance rate towards the values found for normal women.