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Studies on peptidase enzymes in human endometrium and placenta

人子宫内膜和胎盘肽酶的研究

基本信息

批准号：
05454448
负责人：
KANZAKI Hideharu
金额：
$ 2.82万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

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

人子宫内膜表达氨肽酶 N (APN)、中性肽链内切酶 (NEP) 和二肽基肽酶 IV (DPPIV) 的细胞表面肽酶抗原。通过特异性单克隆抗体的间接免疫荧光染色，揭示这些肽酶的表达具有细胞类型特异性，并且在月经周期和妊娠期间动态变化。 APN和NEP在子宫内膜基质细胞上表达，在增殖期表达较弱。排卵后，APN表达增加，妊娠早期蜕膜细胞表达很强的APN抗原。 NEP也在分泌期增加，在蜕膜化后逐渐减少。 DPPIV 只在腺上皮细胞上表达，最突出的表达出现在分泌中期，表明其在囊胚植入中的作用。这些发现表明子宫内膜细胞肽酶表达的激素控制，以及纯化基质细胞的体外培养表明孕酮和雌激素在诱导 APN 抗原表达以及该酶的生物活性中的重要作用。当将 APN 抑制剂贝斯汀 (bestatin) 添加到黄体酮诱导的体外基质细胞分化（蜕膜化）系统中时，催乳素产生和形态转化所指示的细胞分化受到剂量依赖性抑制。因此APN也是子宫内膜细胞分化的重要分子。孕早期绒毛膜绒毛细胞滋养细胞同时表达NEP和DPPIV,而合体滋养细胞仅表达NEP。绒毛膜间质细胞表达不同强度的APN、NEP和DPPIV。足月胎盘中，绒毛合体滋养细胞弱表达NEP，绒毛基质细胞强表达APN和DPPIV。由此表明，三种肽酶是子宫内膜和胎盘细胞非常有用的标记物，是子宫内膜生理和妊娠维持的重要分子。较少的