The roles of pregn-5-ene-3β20α-diol and 20α-hydroxy steroid dehydrogenase in the control of progesterone synthesis preceding parturition and lactogenesis in the rat

摘要

1. The activity of 20α-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 3β-hydroxy Δ⁵-steroid dehydrogenase decreased by 50% at parturition but remained constant at other times. 2. The 20α-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-3β,20α-diol and then to 20α-hydroxypregn-4-en-3-one by 20α-hydroxy steroid dehydrogenase and 3β-hydroxy Δ⁵-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 20α-hydroxypregn-4-en-3-one as the secreted end product. This is primarily the consequence of the sharp increase in the activity of 20α-hydroxy steroid dehydrogenase. This mechanism is super-imposed on the already declining rate of net Δ⁴-steroid release by the ovary. 5. A relationship of these pathways to subcellular compartments of luteal cells is proposed.