Metabolism of oxytocin in rat uterus and placenta in late gestation.
Concentrations of oxytocin (OT) peptide increase in rat uterine tissues at the time of parturition. We have measured the rate of OT metabolism in these tissues in late gestation to determine whether a decrease in OT catabolism is responsible for the increase in OT concentrations. Uterine and placental tissues were obtained from groups of rats at Days 16, 19, 21, 21.5, 22, and after delivery of the first pup. Delivery usually occurs in the early afternoon of Day 22. Some animals were treated with the estrogen receptor blocker tamoxifen, which will delay parturition by approximately 24 h. Cytosolic and microsomal preparations obtained using ultracentrifugation were incubated with radiolabeled OT. Metabolites were separated using HPLC, and enzyme kinetic parameters were calculated. OT was actively metabolized in both uterine and placental tissues. Total oxytocinase activity was similar in the two tissues. In uterine tissues, activity was greater in the cytosolic fractions. In placenta, activity was evenly distributed between the cytosolic and microsomal fractions. The cytosolic fractions of each tissue contained predominantly post-proline endopeptidase activity, whereas the microsomes contained predominantly aminopeptidase activity. There was a slight trend to decreasing oxytocinase activity with advancing gestation in both subcellular fractions, but this was statistically significant only in the microsomal fraction. The maximal decline in activity was only 25-50%. Tamoxifen treatment had no effect on oxytocinase activity. We conclude that rat uterine and placental tissues contain post-proline endopeptidase and aminopeptidase activities that metabolize OT. It is doubtful that changes in these activities are major factors in regulating the increase in OT concentrations measured in rat intrauterine tissues at the time of parturition.
Mitchell
B F
BF
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Canada. brymitch@gpu.srv.ualberta.ca
Fang
X
X
Wong
S
S
D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D010122:Cystinyl Aminopeptidase / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects / Q000378:metabolism*; D000085822:Prolyl Oligopeptidases; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors; D014599:Uterus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D004965:Estrogen Antagonists; D013629:Tamoxifen; D010121:Oxytocin; D000626:Aminopeptidases; D010122:Cystinyl Aminopeptidase; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases