Placental Leucine Aminopeptidase

  • Seiji Nomura
  • Tomomi Ito
  • Shigehiko Mizutani
Part of the Proteases in Biology and Disease book series (PBAD, volume 2)


Human pregnancy serum and placenta are known to have the ability to degrade oxytocin (OT), the most potent uterotonic peptide. Placental leucine aminopepetidase (P-LAP), which is also called cystine aminopeptidase, is the only membrane aminopeptidase known to open the N-terminal cystine loop of OT. The soluble form of P-LAP present in maternal serum is converted from the membrane-bound form in placenta by an enzyme with metalloprotease activity. The findings that P-LAP activity increases with gestation to counteract the increasing fetus-, placenta- or mother-derived OT and that P-LAP activity is reduced in the patients with preterm delivery suggest a possible role of P-LAP in controlling the uterine contraction. In placenta, P-LAP is expressed in differentiated trophoblasts, which is regulated by the AP-2 and Ikaros transcription factors. Unexpectedly, P-LAP is a homologue of rat insulin-regulated membrane aminopeptidase (IRAP). P-LAP is translocated from the cytosol to the plasma membrane by oxytocin stimulation in vascular endothelial cells and by vasopressin in renal cells, which is similar to the finding that insulin stimulates IRAP translocation in adipocytes. P-LAP has a wide tissue distribution besides placenta, indicating possible roles not related to pregnancy. Since P-LAP hydrolyzes several peptides including vasopressin and angiotensin III other than OT, natural substrates interacting with P-LAP should be considered to elucidate its roles in various pathophysiological processes. Characterization of recently established P-LAP-deficient mice would serve for further elucidation of P-LAP functions. Recently two enzymes significantly homologous to P-LAP have been cloned, which belong to one distinctive group with P-LAP. Therefore, we propose the oxytocinase subfamily of M1 aminopeptidases.

Key words

aminopeptidase oxytocin placenta pregnancy vasopressin 


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Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Seiji Nomura
    • 1
  • Tomomi Ito
    • 1
  • Shigehiko Mizutani
    • 1
  1. 1.Department of Obstetrics and GynecologyNagoya University Graduate School of MedicineNagoyaJapan

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