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Hair Loss Study Abstract: Human prostatic steroid 5 alpha-reductase isoforms--a comparative study of selective inhibitors.
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Title
Human prostatic steroid 5 alpha-reductase isoforms--a comparative study of selective
inhibitors.
Author
Iehlé C; Délos S; Guirou O; Tate R; Raynaud JP; Martin PM
Address
Laboratoire de Cancérologie Expérimentale, Faculté de Médecine, Marseille, France.
Source
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.
Language of Publication
English
Unique Identifier
96042333
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