Temporal changes in activities of enzymes reducing ring-A of progesterone in the fetus and placenta of the rat.

The development of delta4-5alpha-reductase and 3alpha- and 3beta-hydroxysteroid dehydrogenases in rat fetuses and placentas was detected by the production of specific metabolites during in vitro incubation with progesterone. The metabolites, 5alpha-pregnane-3,20-dione, 3alpha-hydroxy-5alpha-pregnan-20-one, and 3beta-hydroxy-5alpha-pregnan-20-one, were identified by isolation and purification by thin-layer chromatography and reverse isotope dilution, followed by recrystallization of the free compound and a derivative. The delta4-5alpha-reductase and the 3beta-hydroxysteroid dehydrogenase are associated with the particulate fraction. However, 3alpha-hydroxysteroid dehydrogenase is a soluble enzyme present in the supernatant fraction of homogenized placentas and fetuses. The activities of these enzymes were greater in the placenta than in the fetus. As pregnancy progresses, the activities increase in the fetus, but diminish in the placenta. Although the placenta secretes only marginal amounts of progesterone, it has a notable capacity to metabolize progesterone to 5alpha-reduced metabolites. The fetus has the ability to utilize progesterone as early as day 13, and its potential to convert progesterone into ring-A reduced products increases during gestation.