Human prostatic steroid 5alpha-reductase isoforms - A comparative study of selective inhibitors
Iehle C.; Delos S.; Guirou O.; Tate R.; Raynaud J.-P.; Martin P.-M. Lab de Cancerologie Experimentale, Faculte de Medecine, Secteur Nord, Bd Pierre Dramard, 13916 Marseille Cedex 20 France

Journal of Steroid Biochemistry and Molecular Biology (United Kingdom), 1995, 54/5-6 (273-279)

The present study describes the independent expression of the type 1 and 2 isoforms of human 5alpha-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 (K(m) = 0.5 and 2.9 microM, respectively). Finasteride and turosteride were selective inhibitors of the type 2 isoform (K(i) (type 2) = 7.3 and 21.7 nM compared to K(i) (type 1) = 108 and 330 nM, respectively). 4-MA and the lipido-sterol extract of Serenoa repens (LSESr) markedly inhibited both isozymes (K(i) (type 1) = 8.4 nM and 7.2 microg/ml, respectively; K(i) (type 2) = 7.4 nM and 4.9 microg/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 5alpha-reductase.
Partially purified recombinant 5alpha-reductase type 1 activity was preserved by the presence of lipids indicating that lipids can exert either stimulatory or inhibitory effects on human 5alpha-reductase.