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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
REVIEW
Discovery of Natural Steroid 5 Alpha-Reductase Inhibitors.
Human steroid 5 alpha-reductases (S5αRs) and NADPH irreversibly reduce testosterone to the more potent dihydrotestosterone (DHT). S5αR inhibitors are useful treatments for DHT-dependent diseases, including benign prostatic hyperplasia, androgenic alopecia and hair growth, and acne. There are three S5αR isozymes, and there is a need for safer and more isozyme selective inhibitors than finasteride and dutasteride currently licensed. In this study, we review the methods used to screen for S5αR inhibitory activity and describe studies that characterize the ability of herbal preparations and their constituents to inhibit S5αRs. We identified enormous variations between studies in IC50 s for finasteride and dutasteride used as standards. Accordingly, we make several recommendations: Stable isozyme specific transfection systems need creating a standardized enzyme/microsome preparation and all three isozymes, as well as androgen receptor binding, should be tested; agreed reaction conditions, especially the substrate concentrations, and separation/quantitation method optimized for high throughput screening; systematic screening of herbal compounds and most extensive use of leads to develop more potent and isozyme specific inhibitors.
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