Metabolism of testosterone-14C by cultured human cells

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Abstract
The metabolism of 14C-labeled testosterone by cultured human fibroblasts and amniotic fluid cells was investigated. Radiolabeled testosterone was incubated with the cultured cells for 48 hr, and the labeled metabolites present in the medium were subsequently identified. The major metabolic products of testosterone formed by cultured fibroblasts were Δ4-androstenedione, dihydrotestosterone, androsterone, and androstanediol. The amount of testosterone metabolized through each of two pathways was calculated and used to form a ratio designated the 17β-hydroxyl/17-ketonic ratio. Fibroblasts from normal male and female children and adult females had high 17β-hydroxyl/17-ketonic ratios indicating testosterone metabolism occurred primarily through the 17β-hydroxyl pathway. There was change in the pattern of testosterone metabolism with age in males, i.e., adult males had much lower 17β-hydroxyl/17-ketonic ratios than did male children. The testosterone metabolism of fibroblast cultures derived from three children with testicular feminization and their mothers was compared to normal age and sexmatched controls. Fibroblasts of children with testicular feminization metabolized testosterone predominantly through the 17-ketonic pathway and manifested a pattern of testosterone metabolism distinctly different from their sex and age matched controls. The mothers of children with testicular feminization could be distinguished from normal females by their much lower 17β-hydroxyl/17-ketonic ratios. The much lower amounts of dihydrotestosterone and androstanediol produced by fibroblasts from patients with testicular feminization as compared with normals suggests there is a decrease in testosterone 5α-reductase activity in these patients. Cultured amniotic fluid cells metabolized testosterone to the same four major metabolites found in fibroblast cultures, but their activity was much lower than that of fibroblasts. Most of the amniotic fluid cell cultures metabolized testosterone largely through the 17β-hydroxyl pathway as did fibroblasts from normal children.