Altered brain and pituitary androgen metabolism by prenatal, perinatal or pre- and postnatal finasteride, flutamide or dihydrotestosterone treatment in juvenile male rats.

1. The authors investigated the administration of finasteride, a 5 alpha-reductase inhibitor; flutamide, an androgen receptor blocker and; exogenous dihydrotestosterone (DHT) during intervals covering different portions of the "critical period" of neural development (i.e. prenatal, perinatal or pre- and postnatal development) to determine the long-term effects of these agents on altering androgen metabolism in hypothalamic and pituitary tissue of juvenile (30 day-old) male rats. 2. The efficacy of the treatments and hypothalamic-pituitary axis function was monitored by measuring luteinizing hormone levels by radioimmunoassay. 5 alpha-Reductase and aromatase activity was determined in hypothalamic and pituitary tissue. 3. Significant alterations in pituitary 5 alpha-reductase activity was detected in DHT-treated animals, whereas, hypothalamic 5 alpha-reductase activity was significantly decreased by finasteride treatment and significantly increased by DHT treatment. Hypothalamic aromatase activity was significantly decreased in flutamide-treated animals. 4. These results suggest that: a) prenatal exposure to exogenous DHT stimulates hypothalamic (but inhibits pituitary) 5 alpha-reductase activity long-term and b) basal 5 alpha-reductase activity levels can be inhibited by finasteride treatment in hypothalamic but not in pituitary tissue, suggesting that a different regulatory mechanism exists for 5 alpha-reductase in hypothalamic versus pituitary tissue.