Influence of 20α-Dihydroprogesterone on Progesterone Output by Human Chorion Explants

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Abstract
The output of progesterone by explants of chorion incubated without exogenous precursor was increased in the presence of 20Α-dihydroprogesterone (20Α-diHP). We have now examined the nature of the 20Α-diHP effect. Explants of chorion were incubated with [3H]progesterone and 3 µM non-radiolabelled 20Α-diHP to examine the effect of 20Α-diHP on progesterone metabolism. Significantly more radioactivity remained as unmetabolized [3H]progesterone compared to chorion incubated in the absence of non-radiolabelled 20Α-diHP. There was also a decrease in the output of [3H]-20Α-diHP by the explants but no change in the output of a second metabolite of progesterone [3H]-5Α-pregnanedione. When explants were incubated with 20Α-diHP in the presence of the 3Β-hydroxysteroid dehydrogenase inhibitor, trilostane, the output of progesterone was significantly greater than with explants incubated with trilostane but without addition of 20Α-diHP. Radiochemically pure [3H]progesterone was produced by explants of chorion incubated with [3H]-20Α-diHP. We conclude that 20Α-diHP may serve as substrate for chorionic progesterone production through 20Α-hydroxysteroid dehydrogenase. 20Α-diHP, formed from progesterone, may also exert product feedback inhibition on this enzyme.