Human prostatic steroid 5 alpha-reductase isoforms—a comparative study of selective inhibitors.


Iehlé C; Délos S; Guirou O; Tate R; Raynaud JP; Martin PM


Laboratoire de Cancérologie Expérimentale, Faculté de Médecine, Marseille, France.


J Steroid Biochem Mol Biol, 54: 5-6, 1995 Sep, 273-9


The present study describes the independent expression of the type 1 and 2 isoforms of human 5 alpha-reductase in thebaculovirus-directed insect cell expression system and the selectivity of their inhibition. The catalytic properties andkinetic parameters of the recombinant isozymes were consistent with published data. The type 1 isoform displayedaneutral (range 6-8) pH optimum and the type 2 isoform an acidic (5-6) pH optimum. The type 2 isoform had higheraffinity for testosterone than did the type 1 isoform (Km = 0.5 and 2.9 microM, respectively). Finasteride andturosteride 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 bothisozymes (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-competitiveinhibition of the type 1 isozyme and uncompetitive inhibition of the type 2 isozyme. These observations suggest that thelipid component of LSESr might be responsible for its inhibitory effect by modulating the membrane environment of 5alpha-reductase. Partially purified recombinant 5 alpha-reductase type 1 activity was preserved by the presence of lipidsindicating 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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