Metabolism of oxytocin in human decidua, chorion, and placenta

Oxytocin (OT) synthesized within human decidua may influence the timing of human parturition. Metabolism of OT within intrauterine tissues may regulate local concentrations. We hypothesized that a decrease in OT metabolism may contribute to an increase in local tissue concentrations around the time of parturition. Thus, we compared OT degradation in human decidua with that in chorion and placenta obtained before or after labor onset at term. We measured kinetic parameters for OT metabolism and determined pathways of degradation. Both cytosol and microsomal fractions contained aminopeptidase and postproline endopeptidase activities. Metabolism in the microsomal fractions was predominantly by an aminopeptidase enzyme that cleaves the ring structure of OT and removes amino acid residues from the N-terminal end. Metabolism in the cytosol fractions was predominantly via postproline endopeptidase activity, which cleaves the C-terminal Leu8-Gly9NH2. The resultant OT-(1-7) also is a substrate for aminopeptidase activity. The apparent maximum 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 < or = 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 significantly greater activity (0.82 +/- 0.22). The Km values for all tissues were in the range of 8-20 mumol/L. There were no significant changes in the kinetic parameters for OT metabolism around the time of labor onset. We conclude that human decidua and chorion as well as placenta actively metabolize OT, but changes in metabolism do not occur around parturition. If increasing decidual concentrations of OT play a role in the timing of human labor onset, mechanisms that increase production or secretion are of primary importance.