Reversal of flutamide-induced cryptorchidism by prenatal time-specific androgens.
The recent discovery of time-specific antiandrogens (flutamide) to induce undescent of the testes has provided us the ability to study androgen therapy for cryptorchidism in the first specific antiandrogen animal model for testicular descent. Postpartal administration of pharmacological doses of testosterone, dihydrotestosterone, or human chorionic gonadotropin failed to reverse antiandrogen-induced cryptorchidism. Reduction in the frequency of testicular undescent occurred only when these agents were administered before parturition. Indeed, statistically significant reductions in the incidence of undescended testes occurred only when androgens were administered simultaneously with the antiandrogens on gestational days 16-17. However, the successful ability of prenatal dihydrotestosterone or testosterone to prevent cryptorchidism was associated with significant complications of prenatal androgen therapy. Specifically, 100% (46 of 46) of the animals that had inhibition of flutamide-induced cryptorchidism manifested findings of hypogonadotropic hypogonadism. The findings of descended diminutive testes and epididymis in these latter animals did, however, substantiate that testicular weight does not play a significant role in descent of this organ. In summary, these studies delineate a narrow window of time in which androgens act to effect testicular descent that is independent of testicular size.
Department of Urology, Mayo Clinic, Rochester, Minnesota 55905.
D A
DA
Husmann
M J
MJ
McPhaul
D000728:Androgens / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D001284:Atrophy; D003456:Cryptorchidism / Q000139:chemically induced / Q000188:drug therapy* / Q000196:embryology; D004338:Drug Combinations; D005260:Female; D005485:Flutamide; D005865:Gestational Age; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011467:Prostate / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000473:pathology
D000728:Androgens; D004338:Drug Combinations; D005485:Flutamide