کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2028534 | 1070424 | 2008 | 8 صفحه PDF | دانلود رایگان |
Inhibition of aromatase activity in human placental microsomes with androstenedione (AD) (1a) and its 19-oxygenated derivatives 1b and 1c, their 16α-hydroxy compounds 2 and 3, and 3-deoxyandrost-4-ene compounds 5 and 6 was studied using [1β-3H]AD as a substrate and compared to that with [1β-3H]16α-hydroxyandrostenedione (16-OHAD). AD series of steroids, compounds 1, inhibited competitively [1β-3H]AD aromatization whereas other 16α-hydroxy steroids 2, 3, 5, and 6 inhibited AD aromatization in a non-competitive manner. On the other hand, all of 16-OHAD series, compounds 2, blocked the [1β-3H]16-OHAD aromatization in a competitive manner whereas the AD series steroids 1 as well as the 3-deoxy-16α-hydroxy-17-one steroids 5 and 3-deoxy-16α,17β-diol steroids 6 inhibited 16-OHAD aromatization non-competitively. 3-Carbonyl and 16α-hydroxy functions of 16-OHAD play a critical role of selection of the 16-OHAD binding site. The results suggest that the AD derivatives 1 are kinetically aromatized at a different site from the 16-OHAD derivatives 2. Physical and/or chemical environments around the aromatase protein in the microsomal membrane may play a significant role in the expression of the substrate specificity, and the present results do not exclude the idea that the placental microsomes have a single binding site.
Journal: Steroids - Volume 73, Issue 12, November 2008, Pages 1262–1269