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

Biochim Biophys Acta. 2005 Aug 1;1751(1):19-25. doi: 10.1016/j.bbapap.2005.04.006.

Abstract

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-2alpha. P-LAP/OTase may be involved in maintaining pregnancy homeostasis via metabolizing peptides such as OT and vasopressin.

Publication types

  • Review

MeSH terms

  • Cystinyl Aminopeptidase / biosynthesis*
  • Cystinyl Aminopeptidase / blood
  • Cystinyl Aminopeptidase / physiology*
  • DNA-Binding Proteins / physiology
  • Female
  • Fetus / enzymology
  • Gene Expression Regulation
  • Humans
  • Ikaros Transcription Factor
  • Labor, Obstetric / physiology
  • Membrane Proteins / metabolism
  • Oxytocin / metabolism*
  • Placenta / enzymology*
  • Pregnancy / physiology*
  • Pregnancy Complications / enzymology
  • Protein Structure, Tertiary
  • Transcription Factor AP-2
  • Transcription Factors / physiology
  • Trophoblasts / enzymology

Substances

  • DNA-Binding Proteins
  • IKZF1 protein, human
  • Membrane Proteins
  • TFAP2A protein, human
  • Transcription Factor AP-2
  • Transcription Factors
  • Ikaros Transcription Factor
  • Oxytocin
  • Cystinyl Aminopeptidase
  • leucyl-cystinyl aminopeptidase