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Hair Loss Study Abstract: Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids.
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Title
Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids.
Author
Liang T; Liao S
Address
Ben May Institute, University of Chicago, IL 60637.
Source
Biochem J, 1992 Jul 15, 285 ( Pt 2):, 557-62
Abstract
Human or rat microsomal 5 alpha-reductase activity, as measured by enzymic conversion of
testosterone into 5 alpha-dihydrotestosterone or by binding of a competitive inhibitor,
[3H]17 beta-NN-diethulcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one ([3H]4-MA) to the
reductase, is inhibited by low concentrations (less than 10 microM) of certain
polyunsaturated fatty acids. The relative inhibitory potencies of unsaturated fatty acids
are, in decreasing order: gamma-linolenic acid greater than
cis-4,7,10,13,16,19-docosahexaenoic acid = cis-6,9,12,15-octatetraenoic acid = arachidonic
acid = alpha-linolenic acid greater than linoleic acid greater than palmitoleic acid
greater than oleic acid greater than myristoleic acid. Other unsaturated fatty acids such
as undecylenic acid, erucic acid and nervonic acid, are inactive. The methyl esters and
alcohol analogues of these compounds, glycerols, phospholipids, saturated fatty acids,
retinoids and carotenes were inactive even at 0.2 mM. The results of the binding assay and
the enzymic assay correlated well except for elaidic acid and linolelaidic acid, the trans
isomers of oleic acid and linoleic acid respectively, which were much less active than
their cis isomers in the binding assay but were as potent in the enzymic assay.
gamma-Linolenic acid had no effect on the activities of two other rat liver microsomal
enzymes: NADH:menadione reductase and glucuronosyl transferase. gamma-Linolenic acid, the
most potent inhibitor tested, decreased the Vmax. and increased Km values of substrates,
NADPH and testosterone, and promoted dissociation of [3H]4-MA from the microsomal
reductase. gamma-Linolenic acid, but not the corresponding saturated fatty acid (stearic
acid), inhibited the 5 alpha-reductase activity, but not the 17 beta-dehydrogenase
activity, of human prostate cancer cells in culture. These results suggest that
unsaturated fatty acids may play an important role in regulating androgen action in target
cells.
Language of Publication
LA=ENG
Unique Identifier
92344638
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