Aromatization of 19-oxygenated androst-4-ene-3,6,17-triones with human placental microsomes.
To gain insight into the aromatization sequence of androst-4-ene-3,6,17-trione (1), a suicide substrate of aromatase, the aromatization of its 19-hydroxy and 19-oxo analogs 2 and 3 with human placental microsomes, was studied using GC-MS. Steroids 2 and 3 were separately incubated with the microsomes in the presence of NADPH in air. The GC-MS analysis of the trimethylsilyl derivative of the aromatization product indicated that both the 19-oxygenated steroids 2 and 3 were aromatized to yield 6-oxoestrogens, 6-oxoestrone (4) and 6-oxoestradiol (5), in each experiment. The aromatization rates of substrates 2 and 3 were 605+/-48 and 1794+/-75 pmol/mg protein/10 min, respectively. These relatively higher rates, compared to that of the parent steroid 1 (73.2+/-6.6 pmol/mg protein/10 min), indicates that the suicide substrate 1 is aromatized through the 19-oxygenated intermediates 2 and 3.
Numazawa
M
M
Tohoku College of Pharmacy, Sendai, Japan.
Sugiyama
T
T
Nagaoka
M
M
D000736:Androstenes / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008861:Microsomes / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
D000736:Androstenes; C018213:androst-4-ene-3,6,17-trione