The roles of pregn-5-ene-3 beta, 20 alpha-diol and 20 alpha-hydroxy steroid dehydrogenase in the control of progesterone synthesis preceding parturition and lactogenesis in the rat.

1. The activity of 20alpha-hydroxy steroid dehydrogenase in rat ovarian corpora lutea increased at least 50-fold between 2 days before and 2 days after parturition, and then fell gradually during lactation. The activity of 3beta-hydroxy Delta(5)-steroid dehydrogenase decreased by 50% at parturition but remained constant at other times. 2. The 20alpha-hydroxypregn-4-en-3-one/progesterone concentration ratio in the ovary fell tenfold between 1 day before and 1 day after parturition, in contrast with the increase of the ratio for these steroids in plasma. 3. Pregnenolone was metabolized in intact cells or cell-free systems either to pregn-5-ene-3beta,20alpha-diol and then to 20alpha-hydroxypregn-4-en-3-one by 20alpha-hydroxy steroid dehydrogenase and 3beta-hydroxy Delta(5)-steroid dehydrogenase respectively, or directly to progesterone by the latter enzyme. The relative activities of these pathways appeared to reflect the relative amounts of the two enzymes and the concentrations of their respective coenzymes NADPH and NAD(+). 4. From these and other observations it was concluded that the cessation of progesterone secretion, which precedes parturition and lactogenesis at the end of pregnancy, is partly due to the redirected metabolism of pregnenolone away from progesterone and towards 20alpha-hydroxypregn-4-en-3-one as the secreted end product. This is primarily the consequence of the sharp increase in the activity of 20alpha-hydroxy steroid dehydrogenase. This mechanism is super-imposed on the already declining rate of net Delta(4)-steroid release by the ovary. 5. A relationship of these pathways to subcellular compartments of luteal cells is proposed.