Enzyme-generated intermediates derived from 4-androstene-3,6,17-trione and 1,4,6-androstatriene-3,17-dione cause a time-dependent decrease in human placental aromatase activity.
Kinetic evidence is presented for a time-dependent decrease in human placental aromatase activity by enzyme-generated intermediates derived from two widely used steroids previously described as competitive inhibitors of estrogen biosynthesis. Thus, 4-androstene-3,6,17-trione binds to the enzyme with an apparent Ki of 0.43 microM and has a pseudo-first order overall rate constant for decrease in activity of 4.03x10(-3)sec-1, while 1,4,6-androstatriene-3,17-dione has an apparent Ki of 0.18 microM and a pseudo-first order overall rate constant for decrease in activity of 1.10x10(-3)sec-1. These findings imply that the potent inhibition of estrogen biosynthesis caused by these steroids results primarily from a decrease in enzyme activity caused by enzyme-generated intermediates from the parent steroids.
D000733:Androstatrienes / Q000378:metabolism* / Q000494:pharmacology; D000736:Androstenes / Q000378:metabolism* / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D010088:Oxidoreductases / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy
D000733:Androstatrienes; D000736:Androstenes; C011658:androsta-1,4,6-triene-3,17-dione; D010088:Oxidoreductases; D001141:Aromatase; C018213:androst-4-ene-3,6,17-trione