Selective inhibition by secosteroids of 5 alpha-reductase activity in human sex skin fibroblasts.
The effects of 5,10-secoestra-4,5-diene-3,10,17-trione (Compound I) and 5,10-seco-19-norpregna-4,5-diene,3,10,20-trione (Compound II) on the 5 alpha-reductase activity and on the androgen receptors of normal human sex skin fibroblasts were investigated. The Vmax and Km of the transformation of testosterone to 5 alpha-reduced products was 387 pg/microgram DNA/30 min and 234 X 10(-9)M, respectively. When the inhibitors were introduced in the assay, the 5 alpha-reductase activity was markedly reduced, Compound I being a less potent inhibitor than Compound II. At 15 min, the inhibition was greater than at 30 and 60 min. The Ki for Compound I was 1.60 x 10(-6)M with a Vmax of 83 to 553 pg/microgram DNA/30 min. For Compound II, the Ki was 0.53 x 10(-6)M with a Vmax of 70 to 340 pg/microgram DNA/30 min. The inhibition was of the noncompetitive type. Studies with androgen receptors showed that Compound I had a lower affinity for the receptors than Compound II. The ID50 for 3H-DHT and 3H-T for Compound I were 42.9 x 10(-7)M and 8.6 x 10(-7)M, respectively, whereas for Compound II, they were 10.6 x 10(-7)M and 4.8 x 10(-7)M.
D058891:5-alpha Reductase Inhibitors; D001667:Binding, Competitive; D013196:Dihydrotestosterone / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D007231:Infant, Newborn; D007700:Kinetics; D008297:Male; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010413:Penis / Q000201:enzymology; D011944:Receptors, Androgen / Q000378:metabolism; D012632:Secosteroids / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D011944:Receptors, Androgen; D012632:Secosteroids; D013196:Dihydrotestosterone; D013739:Testosterone; D010088:Oxidoreductases