METABOLISM OF OXYTOCIN IN HUMAN DECIDUA, CHORION, AND PLACENTA

Oxytocin (OT) synthesized within human decidua may influence the timin g of human parturition. Metabolism of OT within intrauterine tissues m ay regulate local concentrations. We hypothesized that a decrease in O T metabolism may contribute to an increase in local tissue concentrati ons around the time of parturition. Thus, we compared OT degradation i n human decidua with that in chorion and placenta obtained before or a fter labor onset at term. We measured kinetic parameters for OT metabo lism and determined pathways of degradation. Both cytosol and microsom al fractions contained aminopeptidase and postproline endopeptidase ac tivities. Metabolism in the microsomal fractions was predominantly by an aminopeptidase enzyme that cleaves the ring structure of OT and rem oves amino acid residues from the N-terminal end. Metabolism in the cy tosol fractions was predominantly via postproline endopeptidase activi ty, which cleaves the C-terminal Leu(8)-Gly(9)NH(2). The resultant OT- (1-7) also is a substrate for aminopeptidase activity. The apparent ma ximum velocities of OT metabolism in the cytosol subcellular fractions of decidua (0.87 +/- 0.30 nmol/mg protein . min) and chorion (1.04 +/ - 0.47) were significantly (P less than or equal to 0.05) higher than those in corresponding microsomal fractions (0.17 +/- 0.05 and 0.29 +/ - 0.10, respectively). Placental cytosols (1.08 +/- 0.34) were similar to decidua and chorion, but the microsomal fractions had significantl y greater activity (0.82 +/- 0.22). The K-m values for all tissues wer e in the range of 8-20 mu mol/L. There were no significant changes in the kinetic parameters for OT metabolism around the time of labor onse t. We conclude that human decidua and chorion as well as placenta acti vely metabolize OT, but changes in metabolism do not occur around part urition. If increasing decidual concentrations of OT play a role in th e timing of human labor onset, mechanisms that increase production or secretion are of primary importance.