Urinary steroid metabolites in subjects with male pseudohermaphroditism due to 5α-reductase deficiency

Abstract

To investigate the enzymatic basis for abnormal steroid metabolism in subjects with male pseudohermaphroditism due to 5α-reductase deficiency, the ring A reduced urinary 5β and 5α metabolites of testosterone, androstenedione, 11β-hydroxyandrostenedione, cortisol and corticosterone were measured by gas chromatography. Assays of the four pairs of urinary 5β and 5α steroid metabolites revealed decreased conversion of the parent steroids to 5α-reduced urinary metabolites, with increased 5β to 5α urinary steroid metabolite ratios. These studies establish that increased urinary 5β/5α ratios are distinctive for this disorder, and represent the most reliable method for confirming the diagnosis of primary inherited 5α-reductase deficiency. These data also suggest that the conversion on the many Δ4-3 ketosteroids to 5α-reduced steroids may be due to a single enzyme with broad specificity, or multiple enzyme reductases with a common regulator.