DIFFERENT ASPECTS OF 5α‐REDUCTASE DEFICIENCY IN MALE PSEUDOHERMAPHRODITISM AND HYPOTHYROIDISM

SUMMARYThe 5α‐reductase activity that mediates the transformation of testosterone to dihydrotestosterone in various anatomical sites of human beings, has been studied in different pathological conditions related to 5α‐reductase deficiency. We have studied two patients with male pseudohermaphroditism due to 5α‐reductase deficiency, four patients with the complete form of testicular feminization syndrome and four men with primary hypothyroidism. Results were compared with those obtained in seven normal men. In vivo: radioactive tracers of testosterone were administered to each subject by different routes: intravenous, oral and subcutaneous. The urinary metabolites of these labelled precursors were measured. The 5β: 5α ratios of 17‐ketosteroids (aetiocholanolone: 5α‐androsterone) and androstanediols (5β‐androstane‐3α, 17β‐diol: 5α‐androstane‐3α, 17β‐diol) were calculated in the urine recovered after each mode of administration of radioactive testosterone. When testosterone was administered subcutaneously these ratios were highly increased in one patient with male pseudohermaphroditism due to 5α‐reductase deficiency. In all the other patients, the ratios were found to be in the normal range for men. After oral administration of radioactive testosterone, both 5β: 5α ratios were very high in hypothyroid and in 5α‐reductase deficient patients. These results suggest that the defective 5α‐reductase activity observed in hypothyroid patients is only localized in the hepatic compartment. Conversely, in male pseudohermaphroditism, the 5α‐reductase defect might affect both hepatic and extra‐hepatic compartments. In vitro: the diagnosis of 5α‐reductase deficiency was confirmed in the two male pseudohermaphrodite patients after incubation with 3H testosterone of skin homogenates from the external genital area. No 5α‐reduction of testosterone occurred in the two skin specimens studied. In contrast, 5α‐reductase activity was normal in genital skin from hypothyroid and testicular feminization syndrome patients. In pubic skin, 5α‐reductase activity was absent in patients with testicular feminization syndrome. It was in the normal range in homogenates from hypothyroid patients and varied in the 5α‐reductase deficient patients. Based on these data, it may be postulated that the programming of hepatic and extrahepatic 5α‐reductase enzymes is fundamentally different. In addition, the enzyme that mediates the appearance of secondary sex characteristics seems to be androgen dependent, while the 5α‐reductases present in the external genital area and the liver are not androgen dependent.