Progesterone Metabolism in Digitalis and Other Plants-60 Years of Research and Recent Results

5β-Cardenolides are pharmaceutically important metabolites from the specialized metabolism of Digitalis lanata. They were used over decades to treat cardiac insufficiency and supraventricular tachycardia. Since the 1960s, plant scientists have known that progesterone is an essential precursor of cardenolide formation. Therefore, biosynthesis of plant progesterone was mainly analyzed in species of the cardenolide-containing genus Digitalis during the following decades. Today, Digitalis enzymes catalyzing the main steps of progesterone biosynthesis are known. Most of them are found in a broad range of organisms. This review will summarize the findings of 60 years of research on plant progesterone metabolism with particular focus on the recent results in Digitalis lanata and other plants.