Experiment 569517

Details

PropertyValue
Pharmacology
OrganismSerenoa repens (ARECACEAE)
CitationIEHLE,C: DELOS,S: GUIROU,O: TATE,R: RAYNAUD,JP: MARTIN,PM:. (1995). HUMAN PROSTATIC STEROID 5-ALPHA-REDUCTASE ISOFORMS - A COMPARATIVE STUDY OF SELECTIVE INHIBITORS.. 54()
Amount utilized
Compound isolated
DiseaseTHE PRESENT STUDY DESCRIBES THE INDEPENDENT EXPRESSION OF THE TYPE 1 AND 2 ISOFORMS OF HUMAN 5-ALPHA-REDUCTASE IN THE HACULOVIRUS-DIRECTED INSECT CELL EXPRESSION SYSTEM AND THE SELECTIVITY OF THEIR INHIBITION. THE CATALYTIC PROPERTIES AND KINETI PARAMETERS OF THE RECOMBINENT 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 (4-5) PH EPTIMUM. THE TYPE 2 ISOFORM HAD HIGHER AFFINITY FOR TESTOSTERONE THAN DID THE TYPE 1 ISOFORM (KM = 0.5 AND 2.9 PM, RESPECTIVELY). FLANSTERIDE AND TUROSTEROIDE WERE SELECTIVE INHIBITORS OF THE TYPE 2 ISOFORM(K,(TYPE 2) -7.3 AND 21.7 NM COMPARED TO K1 (TYPE 1) -10% AND 330NM RESPECTIVELY). 4-MA AND THE LIPIDO- STEROL EXTRACTOF SERENOAREPENS(LSHSR)MARKEDLY INHIBITED BOTH ISOZMYES (K (TYPE 1)-8.4 NM AND 7.2MG/ML, RESPECTIVELY; K (TYPE 2)- 7.4 NM AND 4.9MG/ML. RESPECTIVELY. THE THREE AZASTEROIDS WERE COMPETITIVE INHIBITORS VS SUBSTRATE, WHEREAS LSHSR DISPLAYED NON-COMPETITIVE INHIBITION OF THE TYPE 1 ISOXYMS AND UNCOMPETITIVE IHIBITION OF THE TYPE2 ISOZYME. THESE OBSERVATIONS SUGGEST THAT THE LIPID COMPONENT OF LSRSR MITHT BE RESPONSIBLE FOR ITS INHIBITORY EFFECT BY MADULATING 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 STUMULATORY OR INHIBITORY EFFECTS ON HUMAN 5-ALPHA-REDUCTASE
Dose amountVAR
Number1
Qualitative resultACTIVE
AnimalHUMAN ADULT
Dose expressionCONC USED
ExtractHEXANE EXT
GenderMALE