Effect of stanozolol on ?-aminolaevulinic acid synthase and hepatic monooxygenase activity in man and rat

Abstract

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.

Homeostatic Signature of Anabolic Steroids in Cattle Using 1H−13C HMBC NMR Metabonomics

“…Even if normoxic conditions may explain why no increase in hemoglobin concentrations were found in veal calves treated with trenbolone acetate and estradiol, this result does not consider the differential hemoglobin biosynthesis rates in growing animals due to different allometric parameters. So, the lower creatinine excretion in anabolized cattle would be consistent with a plausible increase in hemoglobin biosynthesis rate, since 5-aminolevulinate synthase activity using glycine as substrate is stimulated by androgens and erythropoietin biosynthesis is stimulated by androgens (only in case of aplastic anemia), but is altered by a treatment with estradiol . Such a hypothesis should be tested.…”

Effects of sodium valproate on haem biosynthesis in man: implications for seizure management in the porphyric patient

“…Furthermore, in studies with other drugs (e.g. phenytoin and stanozolol), leucocyte ALA-S activities have been shown to respond in the same way as rat liver ALA-S [10,28]. The origin of the increased urinary porphyrin and precursor excretion is undoubtedly from the liver, indicating increased hepatic haem biosynthesis.…”

“…Many enzyme-inducing drugs such as phenobarbitone act indirectly, causing derepression of ALA-S through an increased requirement for haem for new cyt P450 haemoprotein [5]. Others, such as some steroids, produce direct derepression of the enzyme at transcriptional, translational or processing levels [28,29]. For most drugs, there is an excellent correlation between their ability to increase ALA-S activity in experimental systems and the clinical experience that the same drug will provoke an acute attack in por-phyric patients [4,5].…”