Study of the role of Schiff base formation in the aromatization of 3-[18O]testosterone and 3,17-di-[18O]androstenedione by human placental aromatase.

Testosterone, prepared with 18O at the 3 position, and androstenedione, prepared with 18O at both the 3 and 17 positions, were incubated with human placental microsomes. The resulting estrogen metabolites (estradiol and estrone, respectively) as well as unconverted starting material were isolated and analyzed for their 18O content by gas chromatography-mass spectrometry. In each case, greater than 90% of the 18O present in the original substrate was retained in the products. This result argues against a role for Schiff base formation in the aromatase reaction.