Gene regulation and physiological function of placental leucine aminopeptidase/oxytocinase during pregnancy

Seiji Nomura, Tomomi Ito, Eiko Yamamoto, Seiji Sumigama, Akira Iwase, Mayumi Okada, Kiyosumi Shibata, Hisao Ando, Kazuhiko Ino, Fumitaka Kikkawa, Shigehiko Mizutani

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


Human pregnancy serum and placenta have the ability to degrade uterotonic peptide oxytocin (OT). Placental leucine aminopeptidase (P-LAP), which is also called cystine aminopeptidase, is the only membrane aminopeptidase known to functionally degrade OT as oxytocinase (OTase). P-LAP/OTase hydrolyzes several peptides other than OT including vasopressin and angiotensin III. P-LAP/OTase predicted from cDNA sequence is a type II integral membrane protein, which is converted to a soluble form existing in maternal serum by metalloproteases, possibly ADAM (a disintegrin and metalloproteinase) members. P-LAP/OTase activity increases with normal gestation, while decreases in the patients with preterm delivery and severe preeclampsia. In placenta, P-LAP/OTase is predominantly expressed in differentiated trophoblasts, syncytiotrophoblasts. Activator protein-2 (AP-2) and Ikaros transcription factors play significant roles in exerting high promoter activity of P-LAP/OTase in the trophoblastic cells. Moreover, P-LAP/OTase is transcriptionally regulated in a trophoblast-differentiation-dependent fashion via up-regulation of AP-2, putatively AP-2α. P-LAP/OTase may be involved in maintaining pregnancy homeostasis via metabolizing peptides such as OT and vasopressin.

Original languageEnglish
Pages (from-to)19-25
Number of pages7
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Issue number1
Publication statusPublished - 01-08-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology


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