In vitro inhibition of aromatase by the enantiomers of aminoglutethimide and analogs.
The in vitro aromatase activity in microsomal fractions from rat ovary and its inhibition by enantiomers of aminoglutethimide (AG), rogletimide (RG), and cyclohexylaminoglutethimide (ChAG) were studied by analysing the [3H]H2O released when [1 beta-3H]androstenedione was converted to estrone. Maximum velocity (Vmax) and the Michaelis-Menten constant (Km) of the microsomal aromatase enzyme were 17.40 +/- 0.45 pmol/ml/mg protein/min and 1.02 +/- 0.06 microM, respectively. The IC50s for the enantiomers were similar for (+)-R-AG and (-)-R-ChAG (0.86 +/- 0.06 and 0.89 +/- 0.15 microM, respectively. (+)S-ChAG was most potent with IC50 of 0.075 +/- 0.003 microM. The IC50s for (-)-S-AG, (+)-R-RG, and (-)-S-RG were in the same range (23.15 +/- 2.74, 24.58 +/- 2.46, and 24.43 +/- 2.20 microM, respectively.
Department of Biological and Medical Research (MBC-03), King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
P O
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Ogbunude
H Y
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Aboul-Enein
D000616:Aminoglutethimide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D047072:Aromatase Inhibitors; D005260:Female; D005984:Glutethimide / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008861:Microsomes / Q000201:enzymology; D010053:Ovary / Q000201:enzymology / Q000648:ultrastructure; D051381:Rats; D013237:Stereoisomerism
D047072:Aromatase Inhibitors; D000616:Aminoglutethimide; C088366:cyclohexylaminoglutethimide; C049837:rogletimide; D000735:Androstenedione; D005984:Glutethimide