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

Departments of Obstetrics and Gynecology (S.T., H.A., S.-I.T., M.N., Y.K, S.N., F.K., S.M), and Maternal and Perinatal Medicine (H.A., F.K., S.M.), Nagoya University School of Medicine, Nagoya 466-8550, Japan; Division of Pathology (T.N.), Clinical Laboratory, Nagoya University Hospital, Nagoya 466-8560, Japan; and Laboratory of Cellular Biochemistry (M.T.), The Institute of Physical and Chemical Research (RIKEN), Wako-shi, Saitama 351-0198, Japan

Address all correspondence and requests for reprints to: Hisao Ando, M. D., Ph. D., Department of Obstetrics and Gynecology, Nagoya University School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail: . ando{at}med.nagoya-u.ac.jp

Abstract

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.

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