Finasteride inhibits 5 alpha-reductase activity in human dermal fibroblasts: prediction of its therapeutic application in androgen-related skin diseases. 1995

Q H Nguyen, and T Chen, and X Wang, and Y Chen, and P Chien
Institute of Chemical Biology, University of San Francisco, CA 94117-1080, USA.

BACKGROUND The potential role of finasteride in treating androgen related skin disorders was investigated. METHODS Pooled human dermal fibroblasts were used to assess the effect of finasteride on the 5 alpha-reductase activity in skin tissue. Vmax and Km were estimated in the presence of 0, 10, and 200 nM finasteride. RESULTS Vmax values remain constant near 1.20 pmol/mg protein/h in the presence of increasing concentrations of finasteride; however, apparent Km increases from 0.27 nM at 0 nM finasteride to 0.31 nM and 0.44 nM at 10 nM and 200 nM finasteride, respectively. This suggests that finasteride competes with testosterone and has a high affinity for same binding site of the 5 alpha-reductase enzyme. Apparent Ki was estimated at 282 nM, indicating that a high concentration of finasteride is required to significantly suppress the enzyme activity. CONCLUSIONS This study confirms that finasteride inhibits the conversion of testosterone to dihydrotestosterone in human reticular dermal fibroblasts. Finasteride may have therapeutic potential in treating skin disorders influenced by the action of dihydrotestosterone.

UI MeSH Term Description Entries
D010088 Oxidoreductases The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9) Dehydrogenases,Oxidases,Oxidoreductase,Reductases,Dehydrogenase,Oxidase,Reductase
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005544 Forecasting The prediction or projection of the nature of future problems or existing conditions based upon the extrapolation or interpretation of existing scientific data or by the application of scientific methodology. Futurology,Projections and Predictions,Future,Predictions and Projections
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000726 Androgen Antagonists Compounds which inhibit or antagonize the biosynthesis or actions of androgens. Androgen Antagonist,Antiandrogen,Antiandrogens,Anti-Androgen Effect,Anti-Androgen Effects,Antiandrogen Effect,Antiandrogen Effects,Antagonist, Androgen,Antagonists, Androgen,Anti Androgen Effect,Anti Androgen Effects,Effect, Anti-Androgen,Effect, Antiandrogen,Effects, Anti-Androgen,Effects, Antiandrogen
D000728 Androgens Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power. Androgen,Androgen Receptor Agonist,Androgen Effect,Androgen Effects,Androgen Receptor Agonists,Androgenic Agents,Androgenic Compounds,Agents, Androgenic,Agonist, Androgen Receptor,Agonists, Androgen Receptor,Compounds, Androgenic,Effect, Androgen,Effects, Androgen,Receptor Agonist, Androgen,Receptor Agonists, Androgen

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