Progesterone biosynthesis supported by fatty acid oxidation in the mitochondrial fraction of human term placenta

Oleic acid or oleoyl-CoA in the presence of bovine serum albumin, CoA, ATP, carnitine and malate were found to support progesterone biosynthesis from cholesterol in human term placental mitochondria. This fatty acid-dependent progesterone biosynthesis increased in the presence of adenine nucleotides and decreased after the addition of fluorocitrate. In the presence of rotenone only the stimulatory effect of ATP was maintained, whereas the inhibitory effect of fluorocitrate on the conversion of cholesterol to progesterone was abolished. Similar results were obtained when pyruvate was used as substrate instead of fatty acids. In the presence of antimycin, neither ATP nor fluorocitrate affected significantly the fatty acid-supported progesterone biosynthesis. These results indicate that oxidation of fatty acids stimulates progesterone biosynthesis by increasing the regeneration of the reducing equivalent necessary for the cholesterol side-chain cleavage reaction.