Inhibition of human-type 1 3β-hydroxysteroid deshydrogenase/Δ5-Δ4-isomerase expression using siRNA
Inhibition of human-type 1 3β-hydroxysteroid deshydrogenase/Δ5-Δ4-isomerase expression using siRNA
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DOI：
10.1016/j.jsbmb.2005.01.011
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发表时间：
2005-02-01
影响因子：
4.1
通讯作者：
Luu-The, V
中科院分区：
文献类型：
--
作者：
Samson, M;Labrie, F;Luu-The, V
Specific inhibition of type 1 3 beta-HSD is of particular interest since it will allow us to control the formation of androgens and estrogens in peripheral target tissues without affecting type 2 3 beta-HSD, which is responsible for the biosynthesis of glucocorticoids and mineralocorticoids in the adrenals. The high homology between types 1 and 2 3 beta-HSD is a major difficulty in the development of specific inhibitors through classical chemical synthesis. In this report, we describe the use of small interference RNA (siRNA) to specifically inhibit human type 1 3 beta-HSD. We have constructed three DNA vector-based RNAi vectors that allow us to produce three RNA duplexes of 21 nucleotides targeting three different coding regions of human type 1 3 beta-HSD mRNA. The resulting constructs were co-transfected into HEK-293 cells with a vector expressing type 1 3 beta-HSD. The results indicate that while the two duplexes that target sequences in the 5 '-region do not have a strong inhibitory effect, the duplex that targets the 3 '-region efficiently inhibits 3 beta-HSD activity. Up to 98% inhibition has been observed. To our knowledge, this is the first report showing successful inhibition of steroidogenic enzymes using siRNA technology. (c) 2005 Elsevier Ltd. All rights reserved.
