Studies on peptidase enzymes in human endometrium and placenta

人子宫内膜表达氨基肽酶N(APN)、中性内肽酶(NEP)和二肽基肽酶IV(DPPIV)等细胞表面多肽酶抗原。用特异的单抗进行间接免疫荧光染色，结果表明，这些多肽酶的表达具有细胞特异性，并在月经周期和妊娠过程中动态变化。APN和NEP表达于子宫内膜间质细胞，在增生期表达较弱。排卵后，APN表达增加，早孕蜕膜细胞表达很强的APN抗原。NEP也在分泌期升高，蜕膜化后逐渐下降。DPPIV仅在腺上皮细胞上表达，在分泌中期表达最为明显，提示其在胚泡着床中起重要作用。这些发现提示激素控制子宫内膜细胞多肽酶的表达，并与纯化的基质细胞…体外培养。进一步提示孕酮和雌激素在诱导APN抗原表达和酶的生物活性中起重要作用。当在孕酮诱导的体外基质细胞分化(蜕膜化)系统中加入APN抑制剂Bestatin时，催乳素的产生和形态转化所指示的细胞分化被抑制，并呈剂量依赖关系。因此，APN也是子宫内膜细胞分化的重要分子。在早孕绒毛中，细胞滋养层细胞表达NEP和DPPIV，而合体滋养层细胞仅表达NEP。绒毛基质细胞不同程度地表达APN、NEP和DPPIV。胎盘中，绒毛合体滋养层细胞弱表达NEP，绒毛间质细胞强表达APN和DPPIV，提示这三种多肽酶是子宫内膜和胎盘细胞非常有用的标志物，是子宫内膜生理和妊娠维持的重要分子。较少

Human endometrium expresses cell-surface peptidase antigens of aminopeptidase N (APN), neutral endopeptidase (NEP), and dipeptidyl peptidase IV (DPPIV). By an indirect immunofluorescence staining with specific monoclonal antibodies, it revealed that the expressions of these peptidases are cell-type specific and change dynamically during menstruation cycle and pregnancy. APN and NEP are expressed on endometrial stromal cells, and their expression are weak during proliferative phase. After ovulation, APN expression increases and decidual cells in early pregnancy express very strong APN antigen. NEP also increases during secretory phase and gradually decreases after decidualization. DPPIV is exclusiveiy expressed on glandular epithelial cells, and most prominent expression is seen during mid-secretory phase, suggesting its role in blastocyst implantation. These findings suggest the hormonal control of endometrial cell peptidase expression, and in vitro culture with purified stromal cells … More indicated the important role of progesterone and estrogen in the induction of APN antigen expression as well as biological activity of the enzyme. When a APN inhibitor, bestatin, was added to in vitro stromal cell differentiation (decidualization) system induced by progesterone, cell differentiation indicated by prolactin production and morphological transformation was inhibited dose-dependently. Therefore APN is also an important molecule for endometrial cell differentiation. In the first trimester chorionic villi, cytotrophoblasts expressed both NEP and DPPIV,but syncytiotrophoblasts expressed only NEP.Stromal cells in the chorionic villi expressed APN,NEP and DPPIV at various intensities. In the term placenta, villous syncytiotrophoblasts expressed NEP weakly, and the villous stromal cells intensely expressed APN and DPPIV.Thus it is suggested that three peptidases are very useful marker of endometrial and placental cells, and are important molecules in endometrial physiology and pregnancy maintenance. Less