Anabolic effect of dihydrotestosterone in testicular feminization syndrome

Abstract

Patients with testicular feminization syndrome (TFS) are unresponsive to the masculinizing and anabolic effects of testosterone (T). Conversion of T to dihydrotesterone (DHT) and the binding of these steroids to nuclear chromatin appear to be related to end-organ responsiveness to T. Defective conversion of T to DHT has been observed in TFS. Three siblings with TFS were studied before and after gonadectomy to assess their responsiveness to the anabolic effects of DHT. Daily 24 hr urine nitrogen and phosphorus were measured under metabolic balance conditions before and during DHT administration. Two hypogonadal male patients served as controls. Significant reductions in urinary nitrogen and positive nitrogen balance during DHT were observed in both TFS patients studied prior to gonadectomy. This response was less than that of the controls. Two patients were unresponsive to DHT 3 mo postgonadectomy. Defective conversion of T to DHT would not explain this unresponsiveness of TFS patients to DHT. A more plausable explanation is a deficient affinity of nuclear receptor sites for androgenic steroids. The limited response to DHT in the intact state may be due to summation of endogenous and exogenous androgens or to participation of estrogen in the anabolic response.