TY  - JOUR
PY  - 2002//
TI  - Aromatization of 16alpha-hydroxyandrostenedione by human placental microsomes: effect of preincubation with suicide substrates of androstenedione aromatization
JO  - Journal of steroid biochemistry and molecular biology
A1  - Numazawa, Mitsuteru
A1  - Tachibana, Mii
A1  - Mutsumi, Ayako
A1  - Yoshimura, Akiko
A1  - Osawa, Yoshio
SP  - 165
EP  - 172
VL  - 81
IS  - 2
N2  - Estrogen synthase (aromatase) catalyzes the aromatization of androstenedione (AD) as well as 16alpha-hydroxyandrostenedione (16alpha-OHAD) leading to estrone and estriol, respectively. We found that several steroid analogs including 4-hydroxyandrostenedione (1), 6-oxoandrostenedione (6-oxoAD, 2) and its 19-hydroxy analog (3), 10beta-acetoxyestr-5-ene-7,17-dione (4), androst-5-ene-4,7,17-trione (5), and 17alpha-ethynyl-19-norteststerone (6), which are known suicide inactivators of AD aromatization, are not effective in inactivating 16alpha-OHAD aromatization in a time-dependent manner. The compounds were tested with the use of human placental microsomes and 1beta-tritiated-16alpha-OHAD as the substrate. The results of the tritium water method of 16alpha-OHAD aromatization was confirmed by the gas chromatography-mass spectrometry (GC-MS) method of estriol formation. The 1beta-tritiated-AD was used to measure AD aromatization as a positive control for these experiments. The compounds were tested at concentrations up to 40-fold higher than the K(i)'s determined for inhibition of AD aromatization. These studies suggest that differences exist in the binding site structures responsible for aromatization of 16alpha-OHAD and AD.<p /> <p>Language: en</p>
LA  - en
SN  - 0960-0760
UR  - http://dx.doi.org/10.1016/s0960-0760(02)00060-2
ID  - ref1
ER  -