LOCALIZATION OF NEUTRAL ENDOPEPTIDASE IN THE OVINE UTERUS AND CONCEPTUS DURING THE ESTROUS-CYCLE AND EARLY-PREGNANCY

Neutral endopeptidase (NEP; EC 3.4.24.11), an enzyme which metabolizes several peptides (including oxytocin and endothelins) implicated in t he 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 stro mal cells, in the vasculature in endothelial and vascular smooth muscl e cells, and also weakly in some glandular epithelial cells. In a laye r of stromal fibroblasts several cells in thickness underlying the lum inal epithelium, staining was much weaker than that in the deeper stro mal cells throughout the period examined. NEP staining was also presen t 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 conc eptus, 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 separat ely or remaining untreated, immunohistochemical staining of NEP was st ronger when compared with intact ewes, in caruncular and intercaruncul ar stroma and epithelia, in glands, in the vasculature and in myometri um. The staining was less intense in all cell types in ewes receiving oestrogen plus progesterone. The expression of NEP and its specific re gionalization within the uterus indicate a mechanism by which the avai lability of biologically important peptides involved in the regulation of the oestrous cycle and implantation, including oxytocin and endoth elin, can be controlled by regulation of their metabolism.