Existence of Placental Leucine Aminopeptidase/Oxytocinase/Insulin-Regulated Membrane Aminopeptidase in Human Endometrial Epithelial Cells

Human endometrial epithelial cells are known to express oxytocin receptors around the time of ovulation. Moreover, oxytocin (OT) and OT-induced prostaglandins appear to play a pivotal role in the switching of endometrial glands from the proliferative to the secretory phase. However, there have been few studies of oxytocinase (OTase), which is identical to placental leucine aminopeptidase (P-LAP)/insulin-regulated membrane aminopeptidase (IRAP). We confirmed the expression of P-LAP/OTase in human endometrium and also observed the changes in the expression of P-LAP/OTase throughout the menstrual cycle. P-LAP/OTase and its mRNA were localized in endometrial epithelial cells but not in stromal cells. In the follicular phase, immunoreactive P-LAP/OTase was homogeneously distributed on the plasma membrane and in cytoplasmic granules. Immunoblot analysis demonstrated that the majority of P-LAP/OTase was produced around the time of ovulation. After ovulation, the immunostaining was restricted to the glycogen-rich subnuclear vacuoles, a glandular marker of progesterone release from the corpus luteum. Thereafter, the membrane-bound P-LAP/OTase was released by apocrine secretion during the period of blastocyst implantation and became depleted toward the time of menstruation. Further understanding of the function of P-LAP/OTase in the endometrium appears likely to yield insights into the cyclic changes during the normal menstrual cycle.