Gene regulation and physiological function of placental leucine aminopeptidase/oxytocinase during pregnancy
✍ Scribed by Seiji Nomura; Tomomi Ito; Eiko Yamamoto; Seiji Sumigama; Akira Iwase; Mayumi Okada; Kiyosumi Shibata; Hisao Ando; Kazuhiko Ino; Fumitaka Kikkawa; Shigehiko Mizutani
- Publisher
- Elsevier Science
- Year
- 2005
- Tongue
- English
- Weight
- 309 KB
- Volume
- 1751
- Category
- Article
- ISSN
- 1570-9639
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✦ Synopsis
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-2a. P-LAP/OTase may be involved in maintaining pregnancy homeostasis via metabolizing peptides such as OT and vasopressin.