Iehlé, C and Délos, S and Guirou, O and Tate, R and Raynaud, J P and Martin, P M (1995) Human prostatic steroid 5 alpha-reductase isoforms--a comparative study of selective inhibitors. Journal of Steroid Biochemistry and Molecular Biology, 54 (5-6). pp. 273-279. ISSN 0960-0760Full text not available in this repository. (Request a copy from the Strathclyde author)
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.
|Keywords:||animals, azasteroids, Cholestenone 5 alpha-Reductase, dihydrotestosterone, enzyme activation, enzyme inhibitors, finasteride, insects, isoenzymes, oxidoreductases, prostate, recombinant proteins, transfection, Therapeutics. Pharmacology, Biochemistry, Cell Biology, Endocrinology, Diabetes and Metabolism, Molecular Medicine, Molecular Biology, Endocrinology, Clinical Biochemistry|
|Subjects:||Medicine > Therapeutics. Pharmacology|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Pure Administrator|
|Date Deposited:||02 Nov 2011 11:05|
|Last modified:||27 May 2016 03:49|