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Premenstrual Disappearance of Aminopeptidase A in Endometrial Stromal Cells around Endometrial Spiral Arteries/Arterioles during the Decidual Change

Departments of Obstetrics and Gynecology (H.A., M.N., S.-I.T., Y.K., S.T., Y.M., A.I., S.M.) and Maternal and Perinatal Medicine (H.A., S.M.), Nagoya University School of Medicine, Nagoya 466-8550, Japan; and Division of Pathology, Clinical Laboratory, Nagoya University Hospital (T.N.), Nagoya 466-8560, Japan

Address all correspondence and requests for reprints to: Dr. Hisao Ando, 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

Aminopeptidase A (APA, BP-1) is a membrane-bound zinc metallopeptidase that converts angiotensin II (AngII) into AngIII by selectively hydrolyzing the N-terminal aspartyl residue. AngII has been proposed as a candidate for the initial vasoconstrictor of endometrial spiral arteries/arterioles in the preliminary step of menstruation. In the late secretory phase, endometrial stromal cells (ESC) around the blood vessels begin to differentiate into decidual cells, and AngII has been reported to accumulate around such vessels. However, whether there is a concurrent increase in renin or angiotensin-converting enzyme in this area has not been determined. We hypothesized that APA may be involved in the metabolism of AngII in the cycling endometrium.

Western blot analysis in the present study demonstrated that a considerable amount of APA was present in the secretory phase endometrium. ESC in the secretory phase showed strong expression of APA by immunohistochemical analysis and of APA mRNA by in situ hybridization. In contrast, both APA mRNA and protein were absent in decidual cells. The enzyme activity and the biosynthesis of [³⁵S]methionine-labeled APA significantly decreased during the in vitro decidualization of cultured ESC.

These results suggest that the perivascular disappearance of APA is a differentiation-specific change that occurs along with the decidualization, and that the disappearance of APA might accelerate the accumulation of AngII around the vessels.

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