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.
Lephart
E D
ED
Cecil H. & Ida Green Center, University of Texas Southwestern Medical Center, Dallas.
Husmann
D A
DA
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D018120:Finasteride / Q000494:pharmacology*; D005485:Flutamide / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats
D000728:Androgens; D013196:Dihydrotestosterone; D018120:Finasteride; D005485:Flutamide; D007986:Luteinizing Hormone; D003577:Cytochrome P-450 Enzyme System; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase