Comparative studies of the aromatization of testosterone and epitestosterone by human placental aromatase

The aromatization of epitestosterone (17α-hydroxy- 4-androsten-3-one) and testosterone by lyophilized human placental microsomes was studied. Upon incubation of epitestosterone, 12% was converted to 17α-estradiol, 15% to 19-ketoepitestosterone (17α-hydroxy-4-oxo-4-androsten-19-al), 10% to 19- hydroxyepitestosterone (17α, 19- dihydroxy-4 - androsten- 3- one), and about 10% to several unidentified products. A similar incubation with testosterone resulted in 60% conversion to 17β- estradiol; 30% was unchanged. At increasing substrate concentrations (0.1—50 μM), the aromatization rate of epitestosterone increased gradually and did not reach a plateau, whereas aromatization rate of testosterone plateaued at about 3 μM. The presence of either testosterone or 17β-estradiol in concentrations 0.1—10 times the concentration of epitestosterone inhibited the aromatization of epitestosterone by about 70%, while the aromatization of testosterone was not inhibited by either epitestosterone or 17α-estradiol. Lyophilization of fresh microsomes or storage of the lyophilized microsomes at —20 C greatly reduced the aromatizing activity upon epitestosterone but not upon testosterone. These results suggest that the aromatizing system for epitestosterone is different from that for testosterone.