Effect of stanozolol on delta-aminolaevulinic acid synthase and hepatic monooxygenase activity in man and rat.
Stanozolol is an anabolic steroid which is used in the treatment of aplastic anaemia and has been recently advocated for the prophylaxis of vascular thrombosis. Similar steroid substances stimulate the activity of delta-aminolaevulinic acid synthase (ALA S), the rate limiting enzyme of haem biosynthesis, in rat hepatocytes and chick embryo liver cell cultures and activate acute hepatic porphyria. In the present study stanozolol (10 mg daily for 14 days) has been shown to increase significantly leucocyte ALA S activity in 9 healthy male subjects. There was a concomitant rise in urinary ALA and total porphyrin excretion but no change in antipyrine kinetics or urinary 6 B hydroxycortisol excretion. In a complementary study in male Sprague Dawley rats, stanozolol administered intraperitoneally, produced a dose-dependent increase in hepatic ALA S activity without changing hepatic cytochrome P 450 content. Stanozolol has been clearly shown to elevate ALA S activity, probably directly, and thereby, porphyrin production without affecting hepatic monooxygenase activity. This porphyrinogenic effect may be relevant to the successful treatment of aplastic anaemia with anabolic steroids. Leucocyte ALA S activity may provide a human system for the study of drug porphyrinogenicity in vivo.
D000624:5-Aminolevulinate Synthetase / Q000032:analysis*; D000328:Adult; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D010105:Oxygenases / Q000032:analysis*; D011166:Porphyrins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013197:Stanozolol / Q000494:pharmacology*
D011166:Porphyrins; D013197:Stanozolol; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000624:5-Aminolevulinate Synthetase