Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 273-279 |
| Number of pages | 7 |
| Journal | Journal of Steroid Biochemistry and Molecular Biology |
| Volume | 54 |
| Issue number | 5-6 |
| DOIs | |
| Publication status | Published - 1995 |
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Keywords
- animals
- azasteroids
- Cholestenone 5 alpha-Reductase
- dihydrotestosterone
- enzyme activation
- enzyme inhibitors
- finasteride
- insects
- isoenzymes
- oxidoreductases
- prostate
- recombinant proteins
- transfection
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Human prostatic steroid 5 alpha-reductase isoforms--a comparative study of selective inhibitors. / Iehlé, C; Délos, S; Guirou, O; Tate, R; Raynaud, J P; Martin, P M.
In: Journal of Steroid Biochemistry and Molecular Biology , Vol. 54, No. 5-6, 1995, p. 273-279.Research output: Contribution to journal › Article
TY - JOUR
T1 - Human prostatic steroid 5 alpha-reductase isoforms--a comparative study of selective inhibitors
AU - Iehlé, C
AU - Délos, S
AU - Guirou, O
AU - Tate, R
AU - Raynaud, J P
AU - Martin, P M
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
KW - animals
KW - azasteroids
KW - Cholestenone 5 alpha-Reductase
KW - dihydrotestosterone
KW - enzyme activation
KW - enzyme inhibitors
KW - finasteride
KW - insects
KW - isoenzymes
KW - oxidoreductases
KW - prostate
KW - recombinant proteins
KW - transfection
U2 - 10.1016/0960-0760(95)00134-L
DO - 10.1016/0960-0760(95)00134-L
M3 - Article
VL - 54
SP - 273
EP - 279
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
SN - 0960-0760
IS - 5-6
ER -