ALTERED BRAIN AND PITUITARY ANDROGEN METABOLISM BY PRENATAL, PERINATAL OR PRENATAL AND POSTNATAL FINASTERIDE, FLUTAMIDE OR DIHYDROTESTOSTERONE TREATMENT IN JUVENILE MALE-RATS

1. The authors investigated the administration of finasteride, a 5alph a-reductase inhibitor; flutamide, an androgen receptor blocker and; ex ogenous dihydrotestosterone (DHT) during intervals covering different portions of the ''critical period'' of neural development (i.e. prenat al, perinatal or pre- and postnatal development) to determine the long -term effects of these agents on altering androgen metabolism in hypot halamic and pituitary tissue of juvenile (30 day-old) male rats. 2. Th e efficacy of the treatments and hypothalamic-pituitary axis function was monitored by measuring luteinizing hormone levels by radioimmunoas say. 5alpha-Reductase and aromatase activity was determined in hypotha lamic and pituitary tissue. 3. Significant alterations in pituitary 5a lpha-reductase activity was detected in DHT-treated animals, whereas, hypothalamic 5alpha-reductase activity was significantly decreased by finasteride treatment and significantly increased by DHT treatment. Hy pothalamic 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) 5alp ha-reductase activity long-term and b) basal 5alpha-reductase activity levels can be inhibited by finasteride treatment in hypothalamic but not in pituitary tissue, suggesting that a different regulatory mechan ism exists for 5alpha-reductase in hypothalamic verses pituitary tissu e.