The abnormal development of male sex organs in the rat using a pure antiandrogen and a 5 alpha-reductase inhibitor during gestation

Abstract

The effects of a pure antiandrogen flutamide and the 5 alpha-reductase inhibitor finestaride on both prenatal differentiation of prostate and external genitalia were studied in the rat. In control male offspring the mean value of anogenital distance was 3.1 +/- 0.24 mm, and in control female was 1.2 +/- 0.10 mm. In control male newborn rats, histological sections at cranial portion of the urethra revealed prostate bud formation. Male offspring prenatally exposed to 6 mg/Kg/day of flutamide had a significant decrease in anogenital distance, but no alteration in prostate bud formation. At higher dosages of flutamide, the external genitalia were virtually feminizated and the prostatic budding was completely inhibited. In male offspring treated 'in utero' with doses of finestaride of 2, 8 and 16 mg/Kg/day, the anogenital distance became progressively reduced, but complete abolition of prostate development never occurred. However, in male offspring given finestaride at a dose of 2 mg/Kg/day concomitantly with flutamide at a dose of 6 mg/Kg/day, prostate differentiation was completely abolished.