Selective inhibition of rat epididymal steroid Δ4-5α-reductase> by conjugated allenic 3-oxo-5,10-secosteroids

Abstract The effects of (4 R )-5,10-secoestra-4,5-diene-3,10,17-trione (I) and of (4 R )-5,10-seco-19-norpregna-4.5-diene-3, 10,20-trione (II) on epididymal Δ 4 -5 α -reductase and 3α-hydroxysteroid dehydrogenase were investigated. Assessment by I 50 values showed that Δ 4 -5 α -reductase was inhibited approximately 50 and 250 times more effectively than 3α-hydroxysteroid dehydrogenase by compound I and II respectively. The onset of the inhibition of Δ 4 -5 α -reductase by these compounds occurs in less than five minutes. Both compounds were shown to be non-competitive inhibitors of Δ 4 -5 α -reductase. For Δ 4 -5 α -reductase the K I 's for compounds I and II were 5.47 × 10 −6 and 0.98 × 10 −6 respectively. The results of equilibrium dialysis experiments suggested that the observed Δ 4 -5 α -reductase inhibition was irreversible. The relative specificity of these compounds with respect to inhibitor structure and enzyme inhibition is discussed.