HYPERGLYCEMIA-INDUCED ACTIVATION OF TYPE-1 PROTEIN PHOSPHATASE ACTIVATOR (KINASE F-A) IN PERFUSED HUMAN PLACENTA

We report the identification of type-1 protein phosphatase activating factor (kinase F-A), a unique biologic mediator for both insulin and e pidermal growth factors in the human placenta. The activity of kinase F-A was found to be extremely labile in the unperfused placenta. Fresh term placentas lost more than 50% of the total kinase F-A activity wi thin 6 hours when exposed to air or incubated in medium but not perfus ed. In contrast, the activity of kinase F-A was stable when the human term placenta was dually perfused. This indicates that placental dual perfusion is a useful method for studying protein phosphorylation-deph osphorylation involved in signal transduction. When fresh placentas we re perfused with media containing glucose at 141 +/- 10, 242 +/- 12 an d 436 +/- 20 mg/dL, kinase F-A activity was stimulated several-fold in a glucose concentration-dependent manner when compared with control l evels at delivery. The results suggest that hyperglycemia-mediated act ivation may represent a previously unknown control mechanism for the r egulation of protein kinase F-A. The results also suggest that human p lacental perfusion is a good in vitro system for studying signal trans duction mechanisms involved in hormonal actions and metabolic regulati on.