Inhibition of human placental progesterone synthesis and aromatase activity by synthetic steroidogenic inhibitors in vitro.
The inhibitory effect in vitro of four synthetic steroids on enzyme systems of placental progesterone synthesis at term was analyzed. Cholesterol side chain cleavage enzyme (CSCC) was not influenced by azastene, trilostane, and WIN 32,729. A 50% inhibition of CSCC was found by 10 microM cyanoketone. The 3 beta-hydroxysteroid dehydrogenase was dose-dependently inhibited by azastene (I50 = 1 microM, trilostane (I50 = 4 nM), cyanoketone (I50 = 3 nM), and WIN 32,729 (I50 = 5 nM). A competitive inhibition of the 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSDH) by azastene (I50 = 0.6 microM), trilostane (I50 = 4.1 microM), cyanoketone (I50 = 0.6 microM), and WIN 32,729 (I50 = 1.5 microM) was observed. No difference in the effect of steroids on the 20 alpha-HSDH of early gestational and term placenta was found. The four steroidogenic inhibitors did not affect the activity of placental aromatase in vitro. Our results allow a comparison of inhibitory potencies of four steroidogenic inhibitors on different steroidogenic enzymes in vitro.
D015089:20-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000019:Abortifacient Agents / Q000494:pharmacology*; D000021:Abortifacient Agents, Steroidal / Q000494:pharmacology*; D047072:Aromatase Inhibitors; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008861:Microsomes / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis*
D000019:Abortifacient Agents; D000021:Abortifacient Agents, Steroidal; D047072:Aromatase Inhibitors; D011374:Progesterone; D010088:Oxidoreductases; D015096:3-Hydroxysteroid Dehydrogenases; D015089:20-Hydroxysteroid Dehydrogenases; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D002786:Cholesterol Side-Chain Cleavage Enzyme