Male Pseudohermaphroditism: A Comparative Study of One Patient with 5α-Reductase Deficiency and Three Patients with the Complete Form of Testicular Feminization*

Abstract

One patient with 46 XY pseudohermaphroditism bearing the characteristic phenotype of 5α-reductase deficiency was studied and compared with three patients with the complete form of the testicular feminization syndrome (TF) and seven normal men. The diagnosis of 5α-reductase deficiency was strongly suggested in view of a high ratio of plasma testosterone (T) to dihydrotestosterone. This was emphasized by hCG stimulation. Radioactive traces of differently labeled T were simultaneously administered by iv and percutaneous routes in all subjects, and urinary metabolites were studied. In contrast to what was observed in normal men, the same yield of urinary 5α-andros-tane-3α,17β-diol (Adiol) was found in the patient with presumed 5α-reductase deficiency and the three patients with TF regardless of themode of administration of radioactive T. This could be due to a lack of 5α-reductase in these patients. The 5β to 5α ratio of urinary 17-ketosteroids and androstanediols arising from radioactive T administered either iv or percutaneously was 6–10 times higher in the patient with suspected 5α-reductase deficiency than in TF patients and normal men. These results are in agreement with an enzyme defect affecting both hepatic and extrahepatic compartments in the patient with 5α-reductase deficiency. In vitro, the diagnosis of 5α-reductase deficiency was confirmed after incubation of skin homogenates originating from perineal and pubic sites with [³H]T. No 5α-reduction of T into dihydrotestosterone or 5α-androstane-3α,17β-diol occurred in these two skin specimens, whereas in TF patients, 5α-reductase activity was present only in perineal skin. Specific cytosolic receptor protein was present in the genital skin of the patient with 5α-reductase deficiency, as it was in normal men, whereas it was absent in TF patients. Based on these results, the androgen dependence of 5α-reductase originating from different anatomical sites is discussed.