Prostaglandin E2 9-ketoreductase activity in human decidua vera tissue

Abstract

Amnion is believed to be a tissue of central importance in the biochemical processes of parturition. In this tissue, prostaglandin E2 is the near exclusive prostaglandin produced. And although the production of prostaglandin E2 is increased during labor in women, the levels of the major metabolite of prostaglandin E2 in maternal plasma are not elevated; rather, the levels of 13,14-dihydro-15-ketoprostaglandin F2α, the major circulating metabolite of prostaglandin F2α, are increased strikingly. Because of this apparent paradox, we considered the possibility that prostaglandin E2, originating in amnion, chorion laeve, or decidua vera, is converted to prostaglandin F2α in decidua vera by the action of prostaglandin E2-9-ketoreductase. We found that prostaglandin E2 9-ketoreductase, the enzyme that catalyzes the conversion of prostaglandin E2 to F2α, is present in cytosolic fractions prepared from homogenates of uterine decidua vera tissue. The specific activity of 9-ketoreductase in cytosolic fractions of decidua of six women varied from 3.2 to 155 pmol × min−1 × mg−1 protein. We also evaluated the conversion of exogenous prostaglandin E2 to F2α in intact human endometrial stromal cells in monolayer culture. We found that prostaglandin E2, added to the culture medium, was converted to prostaglandin F2α by endometrial stromal cells that were maintained in the presence of inhibitors of prostaglandin synthase. The extent of conversion of exogenous prostaglandin E2 to F2α, however, was low relative to the specific activity of prostaglandin E2 9-ketoreductase found in decidual cytosol. These findings are consistent with the possibility that prostaglandin E2 formed in decidua vera tissue may be converted in that tissue to prostaglandin F2α by 9-ketoreductase; on the other hand, prostaglandin E2 formed in contiguous tissues probably is not converted significantly to prostaglandin F2α by decidual 9-ketoreductase.