Expression of aminopeptidase N in human endometrium and regulation of its activity by estrogen.

ABSTRACT

OBJECTIVES: To determine whether aminopeptidase N (APN) regulates the cycle-dependent bioavailability of interleukin-8 (IL-8) in the endometrium. DESIGN: Prospective study. SETTING: University medical center. PATIENT(S) Women without endometrial pathology from the proliferative (n = 25) or secretory (n = 18) phase of the menstrual cycle. INTERVENTION(S) We first immunolocalized APN in the endometrium using an anti-APN antibody. We then determined the regulation of APN kinetic activity by sex steroids in endometrial stromal cell cultures. MAIN OUTCOME MEASURE(S) Expression of APN in human endometrium throughout the menstrual cycle. Regulation of APN activity by estradiol and progesterone in cultured endometrial stromal cells. RESULT(S) Immunohistochemistry of endometrial sections revealed staining of endometrial stroma throughout the menstrual cycle. There was no detectable staining in glandular cells. The expression of APN as detected by immunohistochemistry was significantly lower in the early proliferative phase. In cultured cells, estradiol inhibited APN activity in a concentration-dependent manner. Progesterone did not have a significant effect. CONCLUSION(S) Stromal localization of APN in endometrium may explain the epithelial rather than stromal presence of IL-8 in vivo. Decreased expression of APN may increase IL-8 bioavailability thus contributing to angiogenesis and polymorphonuclear leukocyte chemotaxis in early proliferative phase.