Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9892200 | The Journal of Steroid Biochemistry and Molecular Biology | 2005 | 5 Pages |
Abstract
Specific inhibition of type 1 3β-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 3β-HSD, which is responsible for the biosynthesis of glucocorticoids and mineralocorticoids in the adrenals. The high homology between types 1 and 2 3β-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 3β-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 3β-HSD mRNA. The resulting constructs were co-transfected into HEK-293 cells with a vector expressing type 1 3β-HSD. The results indicate that while the two duplexes that target sequences in the 5â²-region do not have a strong inhibitory effect, the duplex that targets the 3â²-region efficiently inhibits 3β-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.
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Authors
Mélanie Samson, Fernand Labrie, Van Luu-The,