EFFECTS OF 2 NONSTEROIDAL ANTIANDROGENS ON TESTICULAR FUNCTION IN PREPUBERTAL RATS

The effects of two non-steroidal antiandrogens, flutamide and casodex, were evaluated in prepubertal male rats. Animals (23 days old) were s ubcutaneously administered vehicle or 1, 2, 5, or 10 mg/day of flutami de or casodex for 10 days. Testis weights were diminished at the 10 mg /day dose of both antiandrogens. A significant increase in serum lutei nizing hormone (LH) and follicle-stimulating hormone (FSH) levels was detected. Notwithstanding, flutamide influenced LH/FSH levels more sev erely than casodex. No changes were observed in serum prolactin. Serum testosterone, dihydrotestosterone, and 3 alpha-androstanediol levels were increased in flutamide-treated rats from the 2 mg/day dose, where as only 3 alpha-androstanediol was modified at 10 mg/day of casodex, s uggesting a differential effect on androgen metabolism. An elevation o f testicular concentration and basal production of androgens was found , indicating that flutamide and casodex administration are capable of stimulating testicular steroidogenesis, as well as 5 alpha-reduction. However, the in vitro maximal responsiveness of the gonads to human ch orionic gonadotropin was preserved. Antiandrogen administration did no t modify testicular androgen binding protein concentration. In conclus ion, the blockade of androgen action during sexual maturation caused p rofound changes on the pituitary-gonadal axis in male rats.