Gas Chromatography-Mass Spectrometric Study of 19-Oxygenation of the Aromatase Inhibitor 19-Methylandrostenedione with Human Placental Microsomes

• Published in: Biological & Pharmaceutical Bulletin Vol. 29; no. 6; pp. 1242 - 1245
• Main Authors: Mitsuteru NUMAZAWA, Masao NAGAOKA, Wakako HANDA, Akane YAMADA
• Format: Journal Article
• Language: Japanese
• Published: Pharmaceutical Society of Japan 2006
• ISSN: 0918-6158; 1347-5215

To gain insight into the catalytic function of aromatase, we studied 19-Oxygenation of 19-methyl-substituted derivative of the natural substrate androstenedione (AD), compound 1, with human placental aromatase by use of gas chromatography-mass spectrometry (GC-MS). Incubation of the 19-methyl derivative 1 with human pla-cental microsomes in the presence of NADPH under an aerobic condition did not yield a detectable anrount of [19S]19-hydroxy product 2 or its [19R]-isomer 3 when the product was analyzed as the bis-methoxime-trimethylsilyl (TMS) derivative by GC-MS, moreover, the production of estrogen was not detected as the bis-TMS derivative of estradiol (detection limit: about 3 ng and 10 pg per injection for the 19-ol and estradiol, respectively). The results reveal that the 19-methyl steroid 1 does not serve as a substrate of aromatase, although it does serve as a powerful inhibitor of the enzyme.