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Saw Palmetto Human prostatic steroid 5 alpha-reductase
isoforms--a comparative study of selective inhibitors.
This study suggests that Fenistride (active
ingredient of Propecia) only inhibited the Type 2 form of 5 alpha reductase
where Saw Palmetto extract inhibited both type 1 and 2 forms of 5 alpha-reductase
and was more potent than Fenistride.
Author: Iehlé C; Délos S; Guirou O; Tate
R; Raynaud JP; Martin PM
Journal: J Steroid Biochem Mol Biol, 54:
5-6, 1995 Sep, 273-9
Abstract: The present study describes the
independent expression of the type 1 and 2 isoforms of human 5 alpha-reductase
in the baculovirus-directed insect cell expression system and the selectivity of
their inhibition. The catalytic properties and kinetic parameters of the
recombinant isozymes were consistent with published data. The type 1 isoform
displayed a neutral (range 6-8) pH optimum and the type 2 isoform an acidic
(5-6) pH optimum. The type 2 isoform had higher affinity for testosterone than
did the type 1 isoform (Km = 0.5 and 2.9 microM, respectively). Finasteride and
turosteride were selective inhibitors of the type 2 isoform (Ki (type 2) = 7.3
and 21.7 nM compared to Ki (type 1) = 108 and 330 nM, respectively). 4-MA and
the lipido-sterol extract of Serenoa repens (LSESr) markedly inhibited both
isozymes (Ki (type 1) = 8.4 nM and 7.2 micrograms/ml, respectively; Ki (type 2)
= 7.4 nM and 4.9 micrograms/ml, respectively). The three azasteroids were
competitive inhibitors vs substrate, whereas LSESr displayed non-competitive
inhibition of the type 1 isozyme and uncompetitive inhibition of the type 2
isozyme. These observations suggest that the lipid component of LSESr might be
responsible for its inhibitory effect by modulating the membrane environment of
5 alpha-reductase. Partially purified recombinant 5 alpha-reductase type 1
activity was preserved by the presence of lipids indicating that lipids can
exert either stimulatory or inhibitory effects on human 5 alpha-reductase.
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