Effect of flutamide on 5 alpha-reductases, 5 beta-reductases, and 3-hydroxysteroid dehydrogenases in rat liver.
Flutamide (0.5 mM) decreased in vitro the activity of NADH-5 alpha-reductase (substrate testosterone) in liver homogenate of male and female rats, whereas no change of activity of NADPH-5 alpha-reductase was observed. NADH- and NADPH-5 beta-reductase activity increased only in liver of female, but not of male rats. NAD+-3 beta-hydroxysteroid dehydrogenase and NAD+-3 alpha-hydroxysteroid dehydrogenase (substrate 5 alpha-dihydro-testosterone) in liver homogenate from female rats were inhibited by flutamide (0.5 mM), whereas the activity of NADP+-3 alpha-hydroxysteroid dehydrogenase (substrate 5 alpha-dihydrotestosterone) and of NAD+-3 alpha-hydroxysteroid dehydrogenase (substrate 5 beta-dihydrotestosterone) increased in presence of flutamide. The activity of NADH- and NADPH-5 alpha-reductase decreased after flutamide administration to female rats at a dose of 5 mg per day for 7 days.
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D042944:Cholestenone 5 alpha-Reductase; D005260:Female; D005485:Flutamide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013256:Steroids / Q000378:metabolism*
D000813:Anilides; D013256:Steroids; D005485:Flutamide; D010088:Oxidoreductases; D015096:3-Hydroxysteroid Dehydrogenases; D042944:Cholestenone 5 alpha-Reductase; C021936:3-oxo-5 beta-steroid delta 4-dehydrogenase