Riley S C, Wong E, Findlay J K, Salamonsen L A
Prince Henry's Institute of Medical Research, Clayton, Vic., Australia.
Reprod Fertil Dev. 1995;7(1):27-33. doi: 10.1071/rd9950027.
Neutral endopeptidase (NEP; EC 3.4.24.11), an enzyme which metabolizes several peptides (including oxytocin and endothelins) implicated in the control of uterine function, was found to be localized in the ovine uterus throughout the oestrous cycle and in the uterus and conceptus during early pregnancy, using immunohistochemical techniques. Positive NEP immunoreactivity was found in the endometrium principally in stromal cells, in the vasculature in endothelial and vascular smooth muscle cells, and also weakly in some glandular epithelial cells. In a layer of stromal fibroblasts several cells in thickness underlying the luminal epithelium, staining was much weaker than that in the deeper stromal cells throughout the period examined. NEP staining was also present in smooth muscle cells of the myometrium at all times, and was most intense in the layer of cells adjacent to the endometrium. In the conceptus, NEP immunohistochemical staining was found in uninucleate cells, but not in binucleate trophoblast cells, in epithelial cells of the allantois and amnion, and in the heart and brain of the Day-20 embryo. In ovariectomized ewes treated with oestrogen or progesterone separately or remaining untreated, immunohistochemical staining of NEP was stronger when compared with intact ewes, in caruncular and intercaruncular stroma and epithelia, in glands, in the vasculature and in myometrium. The staining was less intense in all cell types in ewes receiving oestrogen plus progesterone. The expression of NEP and its specific regionalization within the uterus indicate a mechanism by which the availability of biologically important peptides involved in the regulation of the oestrous cycle and implantation, including oxytocin and endothelin, can be controlled by regulation of their metabolism.
中性内肽酶（NEP；EC 3.4.24.11）是一种可代谢多种与子宫功能调控相关肽类（包括催产素和内皮素）的酶。采用免疫组织化学技术发现，在整个发情周期中，该酶定位于绵羊子宫，在妊娠早期则定位于子宫和孕体。NEP免疫反应阳性主要见于子宫内膜的基质细胞、血管的内皮细胞和血管平滑肌细胞，部分腺上皮细胞也有弱阳性反应。在腔上皮下方一层厚度为几个细胞的基质成纤维细胞中，在所研究的整个时期内，染色均比深层基质细胞弱得多。NEP染色在子宫肌层的平滑肌细胞中也始终存在，且在与子宫内膜相邻的细胞层中最为强烈。在孕体中，NEP免疫组织化学染色见于单核细胞，但不见于双核滋养层细胞，在尿囊和羊膜的上皮细胞以及20日龄胚胎的心脏和大脑中也有发现。在分别用雌激素或孕激素处理或未处理的去卵巢母羊中，与未处理母羊相比，NEP免疫组织化学染色在肉阜和肉阜间的基质、上皮、腺体、血管和子宫肌层中更强。在接受雌激素加孕激素处理的母羊中，所有细胞类型的染色强度均较低。NEP的表达及其在子宫内的特定区域定位表明，一种机制可通过调节参与发情周期和着床调节的生物活性重要肽（包括催产素和内皮素）的代谢来控制其可用性。
