title: Inhibition of aromatase activity in the rat by aminoglutethimide and related compounds.
abstract: Two compounds possessing aromatase inhibitory activity have been evaluated for their effects on oestradiol (E2) biosynthesis in the rat. These compounds, structurally related to aminoglutethimide (1), were administered intra-peritoneally at two dose levels to 10 week old female rats previously treated with pregnant mares' serum gonadotrophin (PMSG, 100 i.u. subcutaneously every other day for 9 days). Three hours after dosing, blood was collected and plasma oestradiol levels determined by RIA. Aminoglutethimide, 3-(4'-aminophenyl-3-ethylpyrrolidine-2,5-dione (2) and N-methyl-3-(4'-aminophenyl)-3-ethylpyrrolidine-2,5-dione (3) decreased E2 blood levels by 98, 97 and 82% of control levels respectively (n = 6) at a dose of 50 mg/kg. Similarly effective inhibition was also observed at a dose of 25 mg/kg (n = 4). Ovarian aromatase activity, assessed by incubating the homogenised ovaries of treated rats with tritium-labelled androstenedione (0.2 microM) or testosterone (1 microM), indicated that residual enzyme activity was reduced compared with controls. Aminoglutethimide, and the new pyrrolidinedione aromatase inhibitors 2 and 3, are therefore effective inhibitors of E2 biosynthesis in the rat with functioning ovarian activity.
mesh_terms: D000616:Aminoglutethimide / Q000031:analogs & derivatives / Q000494:pharmacology*; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D047072:Aromatase Inhibitors; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D010053:Ovary / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000378:metabolism
chemical_list: D047072:Aromatase Inhibitors; D000616:Aminoglutethimide; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; C052372:3-(4'-aminophenyl)-3-ethylpyrollidine-2,5-dione; C052373:N-methyl-3-(4'-aminophenyl)-3-ethylpyrrolidine-2,5-dione